NOVEL BENZO-1,3-DIOXOLYL- AND BENZOFURANYL SUBSTITUTED PYRROLIDINE DERIVATIVES AS ENDOTHELIN ANTAGONISTS

Abstract: A compound of formula (I), or a pharmaceutically acceptable salt thereof is disclosed, as well as processes for and intermediates in the preparation thereof, and a method of antagonizing endothelin.

Description: NOVEL BENZO-1.3-DIOXOLYL- AND BENZOFURANYL SUBSTITUTED PYRROLIDINE DERIVATIVES AS ENDOTHELIN ANTAGONISTS This is a continuation-in-part of U.S. patent application Serial No. 5 08/600,625, filed February 13, 1996, which is a continuation-in-part of U.S. patent application Serial No. 08/497,998, filed August 2, 1995, which is a continuation-in-part of U.S. patent application Serial No. 08/442,575, filed May 30, 1995, which is a continuation-in-part of U.S. patent application Serial No. 08/334,717, filed November 4, 1994, ι o which is a continuation-in-part of U.S. patent application Serial No. 08/293,349, filed August 19, 1994. Technical Field The present invention relates to compounds which are endotheiin 15 antagonists, processes for making such compounds, synthetic intermediates employed in these processes and methods and compositions for antagonizing endotheiin. Background of the Invention 20 Endotheiin (ET) is a 21 amino acid peptide that is produced by endothelial cells. ET is produced by enzymatic cleavage of a Trp-Val bond in the precursor peptide big endotheiin (Big ET). This cleavage is caused by an endotheiin converting enzyme (ECE). Endotheiin has been shown to constrict arteries and veins, increase mean arterial blood 25 pressure, decrease cardiac output, increase cardiac contractility in vitro, stimulate mitogenesis in vascular smooth muscle cells in vitro, contract non-vascular smooth muscle including guinea pig trachea, human urinary bladder strips and rat uterus in vitro, increase airway resistance in vivo, induce formation of gastric ulcers, stimulate 30 release of atrial natriuretic factor in vitro and in vivo, increase plasma levels of vasopressin, aldosterone and catecholamines, inhibit release of renin in vitro and stimulate release of gonadotropins in vitro. It has been shown that vasoconstriction is caused by binding of endotheiin to its receptors on vascular smooth muscle (Nature 332 411 35 (1988), FEBS Letters 23J_ 440 (1988) and Biochem. Biophys. Res. Commun. 154 868 (1988)). An agent which suppresses endotheiin production or an agent which binds to endotheiin or which inhibits the binding of endotheiin to an endotheiin receptor will produce beneficial effects in a variety of therapeutic areas. In fact, an anti-endothelin antibody has been shown, upon intrarenal infusion, to ameliorate the adverse effects of renal ischemia on renal vascular resistance and glomerular filtration rate (Kon, et al., J. Clin. Invest. £3, 1762 (1989)). In addition, an anti-endothelin antibody attenuated the nephrotoxic effects of intravenously administered cyclosporin (Kon, et al., Kidney Int. 3Z. 1487 (1990)) and attenuated infarct size in a coronary artery ligation-induced myocardial infarction model (Watanabe, et al., Nature Clozel et al. (Nature 365: 759-761 (1993)) report that Ro 46- 2005, a nonpeptide ET-A/B antagonist, prevents post-ischaemic renal vasoconstriction in rats, prevents the decrease in cerebral blood flow due to subarachnoid hemorrhage (SAH) in rats, and decreases MAP in sodium-depleted squirrel monkeys when dosed orally. A similar effect of a linear tripeptide-like ET-A antagonist, BQ-485, on arterial caliber after SAH has also been recently reported (S.ltoh, T. Sasaki, K. Ide, K. Ishikawa, M. Nishikibe, and M. Yano, Biochem. Biophys. Res. Comm. , 195: 969-75 (1993). These results indicate that agents which antagonize ET/ET receptor binding will provide therapeutic benefit in the indicated disease states. Agents with the ability to antagonize ET/ET receptor binding have been shown to be active in a number of animal models of human disease. For example, Hogaboam et al (EUR. J. Pharmacol. 1996, 309. 261-269), have shown that an endotheiin receptor antagonist reduced injury in a rat model of colitis. Aktan et al (Transplant Int 1996, 9_, 201-207) have demonstrated that a similar agent prevents ischemia-repurfusion injury in kidney transplantation. Similar studies have suggested the use of endotheiin antagonists in the treatment of angina, pulmonary hypertension, raynaud's disease, and migraine. (Ferro and Webb, Drugs 1996, 5.1, 12-27). Abnormal levels of endotheiin or endotheiin receptors have also been associated with a number of disease states, including prostate cancer (Nelson et al, Nature Medicine 1995, 1 , 944-949), suggesting a role of endotheiin in the pathophysiology of these diseases. Wu-Wong et al (Lfe Sciences 1996, 58, 1839-1847) have shown that both endotheiin and endotheiin antagonists bind tightly to plasma proteins, e.g., serum albumin. This plasma protein binding can decrease the effectiveness with which the antagonists inhibit endothelin's action. Thus, endotheiin antagonists with reduced plasma protein binding may be more effective than highly bound congeners. Disclosure of the Invention In accordance with the present invention there are compounds of the formula (I): wherein Z is -C(Rιβ)(Ri9)- or -C(O)- wherein Riβ and R19 are independently selected from hydrogen and ioweralkyl; n is 0 or 1 ; R is -(CH2)m-W wherein m is an integer from 0 to 6 and W is (a) -C(0)2-G wherein G is hydrogen or a carboxy protecting group, (b) -PO3H2, (c) -P(0)(OH)E wherein E is hydrogen, Ioweralkyl or arylalkyl, (d) -CN, (e) -C(0)NHRi7 wherein R17 is Ioweralkyl, (f) alkylaminocarbonyl, (g) dialkylaminocarbonyl, (h) tetrazolyl, (i) hydroxy, (j) alkoxy, (k) sulfonamido, (I) -C(0)NHS(0)2Ri6 wherein R16 is Ioweralkyl, haloalkyl, aryl or dialkylamino, (m) -S(0)2NHC(0)Ri6 wherein R 16 is defined as above, Ri and R2 are independently selected from hydrogen, Ioweralkyl, alkenyl, alkynyl, alkoxyalkyi, alkoxycarbonylalkyl, hydroxyalkyi, haloalkyi, haloalkoxyalkyi, alkoxy alkoxyalkyi, thioalkoxyalkoxyalkyi, cycloalkyl, cycloalkylalkyl, aminocarbonylalkyl, alkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, aminocarbonylalkenyl, alkyiaminocarbonylalkenyl, dialkylaminocarbonylalkenyl, hydroxyalkenyl, aryl, arylalkyl, aryloxyaikyl, arylalkoxyalkyl, (N-alkanoyl-N-alkyl)aminoalkyl, alkylsulfonylamidoalkyl, heterocyclic, (heterocyclic)alkyl and (R aa )(R bb )N-R cc - wherein R aa is aryl or arylalkyi, R bb is hydrogen or alkanoyl and R cc is alkylene, with the proviso that one or both of R- j and R 2 is other than hydrogen; R 3 is (a) R4-C(0)-Rδ- , R4-Rδa- . Rβ-S(0)2- 7- or R 2 6-S(0)-R 2 7- wherein R5 is (i) a covalent bond, (ii) alkylene, (iii) alkenylene, (iv) -N(R2o)-Rβ- or -R 8a -N(R 20 )-R 8 - wherein Re and R 8a are independently selected from the group consisting of alkylene and alkenylene and R20 is hydrogen, Ioweralkyl, alkenyl, haloalkyi, alkoxyalkyi, haloalkoxyalkyi, cylcoalkyl or cycloalkylalkyl or (v) -O-R 9 - or -R 9a -0-R 9 - wherein Rg and R 9a are independently selected from alkylene; R δ a is (i) alkylene or (ii) alkenylene; R7 is (i) a covalent bond, (ii) alkylene, (iii) alkenylene or (iv) -N(R2i )-Rι o- or -R 10a -N(R2i )-Rι o- wherein R10 and R 10a are independently selected from the group consisting of alkylene and alkenylene and R2 1 is hydrogen, Ioweralkyl, alkenyl, haloalkyi, alkoxyalkyi, haloalkoxyalkyi, aryl or arylalkyi; R 4 and Re are independently selected from the group consisting of (i) (Rn)(Ri2)N- wherein R-π and R1 2 are independently selected from (1 ) hydrogen, (2) Ioweralkyl , (3) haloalkyi, (4) alkoxyalkyi, (5) haloalkoxyalkyi , (6) alkenyl, (7) alkynyl, (8) cycloalkyi, (9) cycloalkylalkyl , (10) aryl , (11) heterocyclic, ( 12) arylalkyi, ( 13) (heterocyclic)alkyl, ( 14) hydroxyalkyi, ( 15) alkoxy, (16) aminoalkyl, and (17) trialkylaminoalkyl, (ii ) Ioweralkyl, ( i ii) alkenyl, (iv) alkynyl, (v) cycloalkyi, (vi) cycloalkylalkyl, (vii) aryl , (viii) arylalkyi, (ix) heterocyclic, (x) (heterocyclic)alkyl, (xi) alkoxyalkyi, ( x i i ) hydroxyalkyi, (xiii) haloalkyi, (xiv) haloalkenyl, (xv) haloalkoxyalkyi, (xvi) haloalkoxy, (xvii) alkoxyhaloalkyl, (xviii) alkylaminoalkyl, (xix) dialkylaminoalkyl, (xx) alkoxy, and wherein z is 0-5 and R 7a is alkylene; R2 6 is (i) Ioweralkyl, (ii) haloalkyi, (iii) alkenyl, (iv) alkynyl, (v) cycloalkyi, (vi) cycloalkylalkyl, (vii) aryl, (viii) arylalkyi, (ix) heterocyclic, (x) (heterocyclic)alkyl, (xi) alkoxyalkyi or (xii) alkoxy- substituted haloalkyi; and R27 is alkylene or alkenylene; (b) R22-0-C(0)-R23- wherein R22 is a carboxy protecting group or heterocyclic and R23 is (i) a covalent bond, (ii) alkylene, (iii) alkenylene or (iv) -N(R24)-R25- wherein R25 is alkylene and R 2 4 is hydrogen or Ioweralkyl, (c) Ioweralkyl, (d) alkenyl, (e) alkynyl, (f ) cycloalkyi, (g) cycloalkylalkyl, (h) aryl, (i) arylalkyi, (j ) aryloxyalkyl, (k) heterocyclic, (I) (heterocyclic)alkyl, (m) alkoxyalkyi, (n) alkoxyalkoxyalkyl, or (o) Ri3-C(0)-CH(Rι 4 )- wherein R13 is amino, alkylamino or dialkylamino and R 1 4 is aryl or Ri 5-C(0)- wherein R15 is amino, alkylamino or dialkylamino; or a pharmaceutically acceptable salt thereof. A preferred embodiment of the invention is a compound of formula ( I I) (l l) wherein the substituents -R2, -R and -R1 exist in a trans, trans relationship and Z, n, R, R 1 t R2, and R3 are as defined above. Another preferred embodiment of the invention is a compound of formula (I) or (II) wherein n is 0 and Z is -CH2-. Another preferred embodiment of the invention is a compound of formula (I) or (II) wherein n is 1 and Z is -CH2-. Another preferred embodiment of the invention is a compound of formula (I) or (II) wherein n is 0, Z is -CH2-, and R3 is R 4 -C(0)-R5- , Rβ-S(0)2-R7- or R26-S(0)-R27- wherein R 4 , R 5 , R 6 , R 7 , R 26 and R 27 are as defined above. Another preferred embodiment of the invention is a compound of formula (I) or (II) wherein n is 0, Z is -CH2-, and R3 is alkoxyalkyi or alkoxyalkoxyalkyl. A more preferred embodiment of the invention is a compound of formula (I) or (II) wherein n is 0, Z is -CH2-, and R3 is R4-C(0)-Rs- wherein R4 is (Rn)(Ri2)N- as defined above and R5 is alkylene or R 3 is Rβ-S(0)2-R7- or R26-S(0)-R27- wherein R7 is alkylene, R27 is alkylene and Re and R26 are defined as above. Another more preferred embodiment of the invention is a compound of formula (I) or (II) wherein n is 0, Z is -CH2- and R3 is R4-C(0)-N(R 2 o)-Re- or R 6 -S(0)2-N(R 2 ι)-Rιo- wherein R 8 and R10 are alkylene and R 4 , Re, R20 and R21 are defined as above. An even more preferred embodiment of the invention is a compound of formula (I) or (II) wherein n is 0, R is tetrazolyl or -C(0)2-G wherein G is hydrogen or a carboxy protecting group or R is tetrazolyl or R is -C(0)-NHS(0) 2 R 16 wherein R 16 is Ioweralkyl, haloalkyi or aryl, Z is -CH 2 -, R1 and R2 are independently selected from (i) Ioweralkyl, (ii) cycloalkyi, (iii) substituted aryl wherein aryl is phenyl substituted with one, two or three substituents independently selected from ioweralkyl, alkoxy, halo, alkoxyalkoxy and carboxyalkoxy, (iv) substituted or unsubstituted heterocyclic, (v) alkenyl, (vi) heterocyclic (alkyl), (vii) arylalkyi, (viii) aryloxyalkyl, (ix) (N-alkanoyl-N-alkyl)aminoalkyl and (x) alkylsulfonylamidoalkyl, and R 3 is R 4 -C(0)-Rs- wherein R4 is (Rn)(Ri2)N- wherein R^ and R 12 are independently selected from Ioweralkyl, haloalkyi, alkoxyalkyi, haloalkoxyalkyi, aryl, arylalkyi, heterocyclic, hydroxyalkyi, alkoxy, aminoalkyl, and trialkylaminoalkyl, and R5 is alkylene; or R3 is R4-C(0)-N(R2o)-Rβ- or R6-S(0)2-N(R2i)-Rιo- wherein R4 is Ioweralkyl, aryl, alkoxy, alkylamino, aryloxy or arylalkoxy and Re is Ioweralkyl, haloalkyi, alkoxyalkyi, haloalkoxyalkyi, aryl or arylalkyi, Re and R1 0 are alkylene and R20 and R21 are Ioweralkyl; or R3 is Rβ-S(0)2-R7- or R26-S(0)-R27- wherein Re is Ioweralkyl or haloalkyi, R7 is alkylene, R2 6 is Ioweralkyl and R27 is alkylene. A yet more preferred embodiment of the invention is a compound of formula (I) or (II) wherein n is 0, R is -C(0)2-G wherein G is hydrogen or a carboxy protecting group, tetrazolyl or -C(0)-NHS(0) 2 R 16 wherein R 1 6 is Ioweralkyl, haloalkyi or aryl, Z is -CH2-, R1 is (i) Ioweralkyl, (ii) alkenyl, (iii) alkoxyalkyi, (iv) cycloalkyi, (v) phenyl, (vi) pyridyl, (vii) furanyl, (viii) substituted or unsubstituted 4-methoxyphenyl, 4-fluorophenyl, 3-fluorophenyl, 4-ethoxyphenyl, 4-ethylphenyl, 4-methylphenyl, 4-trifluoromethylphenyl, 4-pentafluoroethyiphenyl, 3-fluoro-4- methoxyphenyl, 3-fluoro-4-ethoxyphenyl, 2-fluorophenyl, 4-methoxymethoxyphenyl, 4-hydroxyphenyl, 4-t-butylphenyl, 1 ,3-benzodioxolyl, 1 ,4- benzodioxanyl or dihydrobenzofuranyl wherein the substituent is selected from alkoxy, alkoxyalkoxy and carboxyalkoxy, (ix) heterocyclic (alkyl), (x) arylalkyi, (xi) aryloxyalkyl, (xii) (N-alkanoyl-N- alkyl)aminoalkyl, or (xiii) alkylsulfonylamidoalkyl, R 2 is substituted or unsubstituted 1 ,3-benzodioxolyl, 7-methoxy-1 ,3-benzodioxolyl, 1 ,4-benzodioxanyl, 8-methoxy-1 ,4-benzodioxanyl, dihydrobenzofuranyl, benzofumayl, 4-methoxyphenyl, dimethoxyphenyl, fluorophenyl or difluorophenyl and R3 is R4-C(0)-N(R 2 o)-R8- or R 6 -S(0) 2 -N(R 2 ι)-Rιo- wherein R 8 and R10 are alkylene, R20 and R21 are Ioweralkyl, R4 is Ioweralkyl, aryl, alkoxy, alkylamino, aryloxy or arylalkoxy and Re is Ioweralkyl, haloalkyi, alkoxyalkyi, aryl or arylalkyi. Another yet more preferred embodiment of the invention is a compound of formula (I) or (II) wherein n is 0, R is -C(0)2-G wherein G is hydrogen or a carboxy protecting group, tetrazolyl or -C(O)- NHS(0) 2 R 16 wherein R 16 is Ioweralkyl, haloalkyi or aryl, Z is -CH2-, R1 is (i) Ioweralkyl, (ii) alkenyl, (iii) alkoxyalkyi, (iv) cycloalkyi, (v) phenyl, (vi) pyridyl, (vii) furanyl, (viii) substituted or unsubstituted 4-methoxyphenyl, 4-fluorophenyl, 3-fluorophenyl, 4-ethoxyphenyl, 4-ethylphenyl, 4-methylphenyl, 4-trifluoromethylphenyl, 4-pentafluoroethylphenyl, 3-fluoro-4- methoxyphenyl, 3-f luoro-4-ethoxy phenyl , 2-f luorophenyl , 4-methoxymethoxy phenyl , 4-hydroxyphenyl, 4-t-butylphenyl, 1 ,3-benzodioxolyl, 1 ,4- benzodioxanyl or dihydrobenzofuranyl wherein the substituent is selected from alkoxy, alkoxyalkoxy and carboxyalkoxy, (ix) heterocyclic (alkyl), (x) arylalkyi, (xi) aryloxyalkyl, (xii) (N-alkanoyl-N- alkyl)aminoalkyl, or (xiii) alkylsulfonylamidoalkyl, R 2 is substituted or unsubstituted 1 ,3-benzodioxolyl, 7-methoxy-1 ,3-benzodioxolyl, 1 ,4-benzodioxanyl, 8-methoxy-1 ,4-benzodioxanyl, dihydrobenzofuranyl, benzofurnayl, 4-methoxyphenyl, dimethoxyphenyl, fluorophenyl or difluorophenyl and R3 is R 4 -C(0)-R δ - wherein R5 is alkylene and R4 is (Rn)(Ri2)N- wherein R^ and R 12 are independently selected from Ioweralkyl, haloalkyi, alkoxyalkyi, haloalkoxyalkyi, aryl, arylalkyi, heterocyclic, hydroxyalkyi, alkoxy, aminoalkyl, and trialkylaminoalkyl. Another yet more preferred embodiment of the invention is a compound of formula (I) or (II) wherein n is 0, R is -C(0)2-G wherein G is hydrogen or a carboxy protecting group, tetrazolyl or -C(O)- NHS(0) 2 R 16 wherein R 16 is Ioweralkyl, haloalkyi or aryl, Z is -CH2-, R1 is (i) Ioweralkyl, (ii) alkenyl, (iii) heterocyclic (alkyl), (iv) aryloxyalkyl, (v) arylalkyi, (vi) aryl, (vii) (N-alkanoyl-N- alkyl)aminoalkyl, or (viii) alkylsulfonylamidoalkyl, R 2 is substituted or unsubstituted 1 ,3-benzodioxolyl, 7-methoxy-1 ,3-benzodioxolyl, 1 ,4- benzodioxanyl, 8-methoxy-1 ,4-benzodioxanyl, dihydrobenzofuranyl, benzofurnayl, 4-methoxyphenyl, dimethoxyphenyl, fluorophenyl or difluorophenyl wherein the substituent is selected from Ioweralkyl, alkoxy and halogen and R 3 is R4-C(0)-Rs- wherein R5 is alkylene and R 4 is (Rn )(Ri2)N- wherein R is Ioweralkyl and R 12 is aryl, arylalkyi, hydroxyalkyi, alkoxy, aminoalkyl, trialkylaminoalkyl, or heterocyclic. Another yet more preferred embodiment of the invention is a compound of formula (I) or (II) wherein n is 0, R is -C(0) 2 -G wherein G is hydrogen or a carboxy protecting group, tetrazolyl or -C(O)- NHS(0) 2 R 16 wherein R 16 is Ioweralkyl, haloalkyi or aryl, Z is -CH2-, R 1 is (i) Ioweralkyl, (ii) alkenyl, (iii) heterocyclic (alkyl), (iv) aryloxyalkyl, (v) arylalkyi, (vi) (N-alkanoyl-N-alkyl)aminoalkyl, or (vii) alkylsulfonylamidoalkyl, (vii) phenyl, or (ix) substituted or unsubstituted 4-methoxyphenyl, 3-fluoro-4-methoxyphenyl, 3- fluorophenyl, 3-fluoro-4-ethoxyphenyl, 2-fluorophenyl, 4-methoxymethoxyphenyl, 1 ,3-benzodioxolyl, 1 ,4-benzodioxanyl or dihydrobenzofuranyl wherein the substituent is selected from ioweralkyl, haloalkyi, alkoxy, alkoxyalkoxy and carboxyalkoxy, R 2 is substituted or unsubstituted 1 ,3- benzodioxolyl, 7-methoxy-1 ,3-benzodioxolyl, 1 ,4-benzodioxanyl, 8-methoxy-1 ,4-benzodioxanyl, dihydrobenzofuranyl, 4-methoxyphenyl, dimethoxyphenyl, fluorophenyl or difluorophenyl wherein the substituent is selected from Ioweralkyl, alkoxy and halogen and R3 is Rβ-S(0)2-N(R2i)-Rιo- wherein R10 is alkylene, Re is Ioweralkyl, haloalkyi, alkoxyalkyi, haloalkoxyalkyi, aryl or arylalkyi and R21 is Ioweralkyl, haloalkyi, alkoxyalkyi, haloalkoxyalkyi, aryl or arylalkyi. Another yet more preferred embodiment of the invention is a compound of formula (I) or (II) wherein n is 0, R is -C(0)2-G wherein G is hydrogen or a carboxy protecting group, tetrazolyl or -C(O)- NHS(0) 2 R 1 e wherein R 16 is Ioweralkyl, haloalkyi or aryl, Z is -CH2-, R1 is (i) substituted or unsubstituted 4-methoxyphenyl, 3-fluoro-4-methoxyphenyl, 3-fluorophenyl, 3-fluoro-4-ethoxyphenyl, 4-methoxymethoxyphenyl, 1 ,3-benzodioxolyl or 1 ,4-benzodioxanyl wherein the substituent is selected from Ioweralkyl, haloalkyi, alkoxy and alkoxyalkoxy, (ii) Ioweralkyl, (iii) alkenyl, (iv) 5 heterocyclic (alkyl), (v) aryloxyalkyl, (vi) arylalkyi, (vii) (N-alkanoyl-N- alkyl)aminoalkyl, (viii) alkylsulfonylamidoalkyl, or (ix) phenyl, R 2 is substituted or unsubstituted 1 ,3-benzodioxolyl, 7-methoxy-1 ,3-benzodioxolyl, 1 ,4-benzodioxanyl, 8-methoxy-1 ,4-benzodioxanyl, dihydrobenzofuranyl, 4-methoxyphenyl, ι o dimethoxyphenyl, fluorophenyl or difluorophenyl wherein the substituent is selected from Ioweralkyl, alkoxy and halogen and R3 is alkoxycarbonyl or Rβ-S(0)2-N(R2i)-Rιo- wherein R10 is alkylene, Re is Ioweralkyl, haloalkyi, alkoxyalkyi or haloalkoxyalkyi and R 21 is Ioweralkyl, haloalkyi, alkoxyalkyi or haloalkoxyalkyi. 1 5 Another yet more preferred embodiment of the invention is a = compound of formula (I) or (II) wherein n is 0, R is -C(0)2-G wherein G is hydrogen or a carboxy protecting group, tetrazolyl or -C(O)- NHS(0) 2 R 16 wherein R 16 is Ioweralkyl or haloalkyi, Z is -CH2-, R1 is 20 Ioweralkyl, alkenyl, heterocyclic (allkyl), aryloxyalkyl, aryalkyl, aryl, (N-alkanoyl-N-alkyl)aminoalkyl,, or alkylsulfonylamidoalkyl, and R 3 is R 4 -C(0)-R δ - wherein R δ is alkylene and R4 is (Rπ)(Ri2)N- wherein R and R 12 are independently selected from alkyl, aryl, hydroxyalkyi, alkoxy, aminoalkyl, trialkylaminoalkyl, and heterocyclic. 25 A still more preferred embodiment of the invention is a compound of formula (I) or (II) wherein n is 0, R is -C(0)2-G wherein G is hydrogen or a carboxy protecting group, tetrazolyl or -C(0)-NHS(0) 2 R 16 wherein R 1 6 is Ioweralkyl or haloalkyi, Z is -CH2-, R1 is substituted or 30 unsubstituted 4-methoxyphenyl, 4-fluorophenyl, 2-fluorophenyl, 4-methylphenyl, 4-trifluoromethylphenyl, 4-pentafluoroethylphenyl, 4-methoxymethoxy phenyl, 4-hydroxyphenyl, 4-ethylphenyl, 1 ,3- benzodioxolyl, 1 ,4-benzodioxanyl or dihydrobenzofuranyl wherein the 35 substituent is selected from alkoxy, alkoxyalkoxy and carboxyalkoxy, (ii) Ioweralkyl, (iii) alkenyl, (iv) heterocyclic (alkyl), (v) aryloxyalkyl, (vi) arylalkyi, (vii) (N-alkanoyl-N-alkyl)aminoalkyl, (viii) alkylsulfonylamidoalkyl, or (ix) phenyl, R 2 is 1 ,3-benzodioxolyl, 1 ,4-benzodioxanyl, dihydrobenzofuranyl, benzofuranyl, 4- methoxy phenyl, dimethoxyphenyl, fluorophenyl or difluorophenyl and R3 is R4-C(0)-Rδ- wherein Rδ is alkylene and R4 is (Rn)(Ri2)N- wherein R- j - j and R 12 are independently selected from Ioweralkyl, aryl, arylalkyi, hydroxyalkyi, alkoxy, aminoaikyl, trialkylaminoalkyl, or heterocyclic. Another still more preferred embodiment of the invention is a compound of formula (I) or (II) wherein n is 0, R is -C(0)2-G wherein G is hydrogen or a carboxy protecting group, tetrazolyl or -C(O)- NHS(0) 2 R 1 6 wherein R 1 6 is Ioweralkyl or haloalkyi, Z is -CH2-, R1 is Ioweralkyl, alkenyl, heterocyclic (alkyl), aryloxyalkyl, arylalkyi, (N- alkanoyl-N-alkyl)aminoalkyl, alkylsulfonylamidoalkyl, phenyl, or alkoxyalkyi, R 2 is 1 ,3-benzodioxolyl, 1 ,4-benzodioxanyl, dihydrobenzofuranyl, benzofuranyl, 4-methoxy phenyl, dimethoxyphenyl, fluorophenyl or difluorophenyl and R 3 is R 4 -C(0)-Rδ- wherein Rδ is alkylene and R4 is (Rn)(Ri2)N- wherein R and R 12 are independently selected from Ioweralkyl, aryl, arylalkyi, hydroxyalkyi, alkoxy, aminoaikyl, trialkylaminoalkyl, or heterocyclic. A most highly preferred embodiment of the invention is a compound of formula (I) or (II) wherein n is 0, R is -C(0)2-G wherein G is hydrogen or a carboxy protecting group, Z is -CH2-, R1 is substituted or unsubstituted 4-methoxyphenyl, 4-fluorophenyl, 2-fluorophenyl, 4-methylphenyl, 4-trifluoromethylphenyl, 4-pentafluoroethylphenyl, 4-methoxymethoxyphenyl, 4-hydroxyphenyl, 4-ethylphenyl, 1 ,3- benzodioxolyl, 1 ,4-benzodioxanyl or dihydrobenzofuranyl wherein the substituent is selected from alkoxy, alkoxyalkoxy and carboxyalkoxy, R 2 is 1 ,3-benzodioxolyl, 1 ,4-benzodioxanyl, dihydrobenzofuranyl, benzofuranyl, 4- methoxyphenyl, dimethoxyphenyl, fluorophenyl or difluorophenyl and R 3 is R4-C(0)-Rδ- wherein R is alkylene and R4 is (Rn)(Ri2)N- wherein R j -, and R 12 are independently selected from Ioweralkyl. Another most highly preferred embodiment of the invention is a compound of formula (I) or (II) wherein n is 0, R is -C(0)2-G wherein G is hydrogen or a carboxy protecting group, Z is -CH 2 -, R1 is substituted or unsubstituted 4-methoxy phenyl, 4-fluorophenyl, 2-fluorophenyl, 4-methylphenyl, 4-trifluoromethylphenyl, 4-pentafluoroethylphenyl, 4-methoxymethoxyphenyl, 4-hydroxyphenyl, 4-ethylphenyl, 1 ,3- benzodioxolyl, 1 ,4-benzodioxanyl or dihydrobenzofuranyl wherein the substituent is selected from alkoxy, alkoxyalkoxy and carboxyalkoxy, R 2 is 1 ,3-benzodioxolyl, 1 ,4-benzodioxanyl, dihydrobenzofuranyl, benzofuranyl, 4- methoxyphenyl, dimethoxyphenyl, fluorophenyl or difluorophenyl and R 3 is R 4 -C(0)-Rs- wherein R5 is alkylene and R4 is (Rn)(Ri 2 )N- wherein R^ is Ioweralkyl and R 12 is aryl. Another most highly preferred embodiment of the invention is a compound of formula (I) or (II) wherein n is 0, R is -C(0)2-G wherein G is hydrogen or a carboxy protecting group, Z is -CH2-, R 1 is substituted or unsubstituted 4-methoxyphenyl, 3-fluoro-4-methoxyphenyl, 3- fluorophenyl, 2-fluorophenyl, 3-fluoro-4-ethoxyphenyl, 4-methoxymethoxyphenyl, 1 ,3-benzodioxolyl, 1 ,4-benzodioxanyl or dihydrobenzofuranyl wherein the substituent is selected from Ioweralkyl, haloalkyi, alkoxy, alkoxyalkoxy and carboxyalkoxy, R 2 is substituted or unsubstituted 1 ,3- benzodioxolyl, 7-methoxy-1 ,3-benzodioxolyl, 1 ,4-benzodioxanyl, 8-methoxy-1 ,4-benzodioxanyl, dihydrobenzofuranyl, 4-methoxyphenyl, dimethoxyphenyl, fluorophenyl or difluorophenyl wherein the substituent is selected from Ioweralkyl, alkoxy and halogen and R3 is R6-S(0)2-N(R2i)-Rιo- wherein R10 is alkylene, Re is Ioweralkyl, haloalkyi, alkoxyalkyi or haloalkoxyalkyi and R21 is Ioweralkyl, haloalkyi or alkoxyalkyi. Another most highly preferred embodiment of the invention is a compound of formula (I) or (II) wherein n is 0, R is -C(0)2-G wherein G is hydrogen or a carboxy protecting group, Z is -CH2-, R1 is substituted or unsubstituted 4-methoxyphenyl, 3-fluoro-4-methoxyphenyl, 3-fluorophenyl, 2-fluorophenyl, 3-fluoro-4-ethoxyphenyl, 4-methoxymethoxyphenyl, 1 ,3-benzodioxolyl, 1 ,4-benzodioxanyl or dihydrobenzofuranyl wherein the substituent is selected from Ioweralkyl, haloalkyi, alkoxy, alkoxyalkoxy and carboxyalkoxy, R 2 is substituted or unsubstituted 1 ,3-benzodioxolyl, 7-methoxy-1 ,3- benzodioxolyl, 1 ,4-benzodioxanyl, 8-methoxy-1 ,4-benzodioxanyl, dihydrobenzofuranyl, 4-methoxy phenyl, dimethoxyphenyl, fluorophenyl or difluorophenyl wherein the substituent is selected from Ioweralkyl, alkoxy and halogen and R3 is R4-C(0)-Rδ- wherein Rδ is alkylene and R4 is (Rn)(Ri2)N- wherein R-, 1 is alkyl and R 12 is selected from aryl, aminoaikyl, trialkylaminoalkyl, and heterocyclic. Another most highly preferred embodiment of the invention is a compound of formula (I) or (II) wherein n is 0, R is -C(0) 2 -G wherein G is hydrogen or a carboxy protecting group, Z is -CH2-, R1 is loweralkyl,alkenyl, heterocyclic (alkyl), aryloxyalkyl, aryalkyl, aryl, (N- alkanoyl-N-alkyl)aminoalkyl, or alkylsulfonylamidoalkyl, and R 3 is R4-C(0)-Rδ- wherein R is alkylene and R4 is (Rn)(Ri2)N- wherein R and Rι 2 are independently selected from alkyl, aryl, hydroxyalkyi, alkoxy, aminoaikyl, trialkylaminoalkyl, and heterocyclic, with the proviso that one or R and R- |2 is alkyl. Another most highly preferred embodiment of the invention is a compound of formula (I) or (II) wherein n is 0, Z is -CH2-, and R3 is R4-C(0)-Rδ- wherein R4 is (Rn)(Ri2)N- as defined therein and R δ is alkylene. Another most highly preferred embodiment of the invention is a compound of formula (I) or (II) wherein n is 0, Z is -CH 2 -, Rl is Ioweralkyl, and R3 is R4-C(0)-Rδ- wherein R4 is (Rn)(Ri2)N- as defined therein and R δ is alkylene. Another most highly preferred embodiment of the invention is a compound of formula (I) or (II) wherein n is 0, Z is -CH2-, Rl is alkenyl, and R3 is R4-C(0)-Rδ- wherein R4 is (Rn)(Ri2)N- as defined therein and R δ is alkylene. Another most highly preferred embodiment of the invention is a compound of formula (I) or (II) wherein n is 0, Z is -CH2-, Rl is heterocyclic (alkyl), and R3 is R4-C(0)-Rδ- wherein R 4 is (Rn)(Ri2)N- as defined therein and Rδ is alkylene. Another most highly preferred embodiment of the invention is a compound of formula (I) or (II) wherein n is 0, Z is -CH2-, Rl is aryloxyalkyl, and R3 is R4-C(0)-Rδ- wherein R4 is (Rn)(Ri2)N- as defined therein and Rδ is alkylene. Another most highly preferred embodiment of the invention is a compound of formula (I) or (II) wherein n is 0, Z is -CH2-, Rl is arylalkyi, and R3 is R4-C(0)-Rδ- wherein R4 is (Rn)(Ri2)N- as defined therein and Rδ is alkylene. Another most highly preferred embodiment of the invention is a compound of formula (I) or (II) wherein n is 0, Z is -CH2-, Rl is aryl, and R3 is R 4 -C(0)-Rδ- wherein R 4 is (Rn)(Ri2)N- as defined therein and R δ is alkylene. Another most highly preferred embodiment of the invention is a compound of formula (I) or (II) wherein n is 0, Z is -CH2-, Rl is (N- alkanoyl-N-alkyl)aminoalkyl, and R3 is R4-C(0)-Rδ- wherein R4 is (Rn)(Ri2)N- as defined therein and Rδ is alkylene. Another most highly preferred embodiment of the invention is a compound of formula (I) or (II) wherein n is 0, Z is -CH2-, R1 is alkylsulfonylamidoalkyl, and R3 is R4-C(0)-Rδ- wherein R4 is (Rn)(Ri2)N- as defined therein and Rδ is alkylene. The present invention also relates to processes for preparing the compounds of formula (I) and (II) and to the synthetic intermediates employed in these processes. The present invention also relates to a method of antagonizing endotheiin in a mammal (preferably, a human) in need of such treatment, comprising administering to the mammal a therapeutically effective amount of a compound of formula (I) or (II). The invention further relates to endotheiin antagonizing 5 compositions comprising a pharmaceutical carrier and a therapeutically effective amount of a compound of formula (I) or (II). The compounds of the invention comprise two or more asymmetrically substituted carbon atoms. As a result, racemic ι o mixtures, mixtures of diastereomers, as well as single diastereomers of the compounds of the invention are included in the present invention. The terms "S" and "R" configuration are as defined by the IUPAC 1974 Recommendations for Section E, Fundamental Stereochemistry, Pure Appl. Chem. (1976) 45, 13 - 30. 15 The term "carboxy protecting group" as used herein refers to a carboxylic acid protecting ester group employed to block or protect the carboxylic acid functionality while the reactions involving other functional sites of the compound are carried out. Carboxy protecting groups are disclosed in Greene, "Protective Groups in Organic Synthesis" 20 pp. 152-186 (1981), which is hereby incorporated herein by reference. In addition, a carboxy protecting group can be used as a prodrug whereby the carboxy protecting group can be readily cleaved in vivo , for example by enzymatic hydrolysis, to release the biologically active parent. T. Higuchi and V. Stella provide a thorough discussion of the 25 prodrug concept in "Pro-drugs as Novel Delivery Systems", Vol 14 of the A.C.S. Symposium Series, American Chemical Society (1975), which is hereby incorporated herein by reference. Such carboxy protecting groups are well known to those skilled in the art, having been extensively used in the protection of carboxyl groups in the penicillin 30 and cephalosporin fields, as described in U.S. Pat. No. 3,840,556 and 3,719,667, the disclosures of which are hereby incorporated herein by reference. Examples of esters useful as prodrugs for compounds containing carboxyl groups can be found on pages 14-21 of "Bioreversible Carriers in Drug Design: Theory and Application", edited 35 by E.B. Roche, Pergamon Press, New York (1987), which is hereby incorporated herein by reference. Representative carboxy protecting groups are Ci to Cβ alkyl (e.g., methyl, ethyl or tertiary butyl and the like); haloalkyi; alkenyl; cycloalkyi and substituted derivatives thereof such as cyclohexyl, cylcopentyl and the like; cycloalkylalkyl and substituted derivatives thereof such as cyclohexylmethyl, cylcopentylmethyl and the like; arylalkyi, for example, phenethyl or 5 benzyl and substituted derivatives thereof such as alkoxybenzyl or nitrobenzyl groups and the like; arylalkenyl, for example, phenylethenyl and the like; aryl and substituted derivatives thereof, for example, 5- indanyl and the like; diaikylaminoalkyl (e.g., dimethylaminoethyl and the like); alkanoyloxyalkyl groups such as acetoxymethyl, butyryloxymethyl, ι o valeryloxymethyl, isobutyryloxymethyl, isovaleryloxymethyl, 1- (propionyloxy)-l -ethyl, 1 -(pivaloyloxyl)-1 -ethyl, 1 -methyl-1 - (propionyloxy)-l -ethyl, pivaloyloxymethyl, propionyloxymethyl and the like; cycloalkanoyloxyalkyl groups such as cyclopropylcarbonyloxymethyl, cyclobutylcarbonyloxymethyl, 5 cyclopentylcarbonyloxymethyl, cyciohexylcarbonyloxymethyl and the like; aroyloxyalkyl, such as benzoyloxymethyl, benzoyloxyethyl and the like; arylalkylcarbonyloxyalkyl, such as benzylcarbonyloxy methyl, 2- benzylcarbonyloxyethyl and the like; alkoxycarbonylalkyl, such as methoxycarbonylmethyl, cyclohexyloxycarbonylmethyl, 1 - 20 methoxycarbonyl-1 -ethyl, and the like; alkoxycarbonyloxyalkyl, such as methoxycarbonyloxymethyl, t-butyloxycarbonyloxymethyl, 1 - ethoxycarbonyloxy-1 -ethyl, 1-cyclohexyloxycarbonyloxy-1 -ethyl and the like; alkoxycarbonylaminoalkyl, such as t-butyloxycarbonylaminomethyl and 25 the like; alkylaminocarbonylaminoalkyl, such as methylaminocarbonylaminomethyl and the like; alkanoylaminoalkyl, such as acetylaminomethyl and the like; heterocycliccarbonyloxyalkyl, such as 4-methylpiperazinylcarbonyloxymethyl and the like; dlalkylaminocarbonylalkyl, such as dimethylaminocarbonylmethyl, 30 diethylaminocarbonylmethyl and the like; (5-(loweralkyl)-2-oxo-1 ,3- dioxolen-4-yl)alkyl, such as (5-t-butyl-2-oxo-1 ,3-dioxolen-4- yl)methyl and the like; and (5-phenyl-2-oxo-1 ,3-dioxolen-4-yl)alkyl, such as (5-phenyl-2-oxo-1 ,3-dioxolen-4-yl)methyl and the like. The term "N-protecting group" or "N-protected" as used herein 35 refers to those groups intended to protect the N-terminus of an amino acid or peptide or to protect an amino group against undersirable reactions during synthetic procedures. Commonly used N-protecting groups are disclosed in Greene, "Protective Groups In Organic Synthesis," (John Wiley & Sons, New York (1981)), which is hereby incorporated by reference. N-protecting groups comprise acyl groups such as formyl, acetyl, propionyl, pivaloyl, t-butylacetyl, 2-chloroacetyl, 2-bromoacetyl, trifluoroacetyl, trichloroacetyl, phthalyl, o-nitrophenoxy acetyl, α-chlorobutyryl, benzoyl, 4-chlorobenzoyl, 4-bromobenzoyl, 4-nitrobenzoyl, and the like; sulfonyl groups such as benzenesulfonyl, p-toluenesulfonyl and the like; carbamate forming groups such as benzyloxycarbonyl, p-chlorobenzyloxycarbonyl, p-methoxybenzyloxycarbonyl , p-nitrobenzy loxycarbonyl , 2-nitrobenzyloxycarbonyl, p-bromobenzyloxycarbonyl, 3,4-dimethoxybenzyloxycarbonyl, 3,5-dimethoxybenzyloxycarbonyl, 2,4-dimethoxybenzyloxycarbonyl, 4-methoxybenzyloxycarbonyl, 2-nitro-4,5-dimethoxybenzyloxycarbonyl, 3,4,5- trimethoxybenzyloxy carbonyl, 1-(p-biphenylyl)-1 -methylethoxycarbonyl, α,α-dimethyl-3,5-dimethoxybenzyloxycarbonyl, benzhydryloxycarbonyl, t-butyloxycarbonyl, diisopropylmethoxycarbonyl, isopropyloxycarbonyl, ethoxycarbonyl, methoxycarbonyl, allyloxycarbonyl, 2,2,2,-trichloroethoxycarbonyl, phenoxycarbonyl, 4-nitrophenoxycarbonyl, fluorenyl-9-methoxycarbonyl, cyclopentyloxycarbonyl, adamantyloxycarbonyl, cyclohexy loxycarbonyl, phenylthiocarbonyl and the like; alkyl groups such as benzyl, triphenylmethyl, benzyloxymethyl and the like; and silyl groups such as trimethylsilyl and the like. Preferred N-protecting groups are formyl, acetyl, benzoyl, pivaloyl, t-butylacetyl, phenylsulfonyl, benzyl, t-butyloxycarbonyl (Boc) and benzyloxycarbonyl (Cbz). The term "alkanoyl" as used herein refers to an alkyl group as previously defined appended to the parent molecular moiety through a carbonyl (-C(O)-) group. Examples of alkanoyl include acetyl, propionyl and the like. The term "alkanoylamino" as used herein refers to an alkanoyl group as previously defined appended to an amino group. Examples alkanoylamino include acetamido, propionylamido and the like. The term "alkanoylaminoalkyl" as used herein refers to R 4 3-NH-R44- wherein R43 is an alkanoyl group and R 4 4 is an alkylene group. The term "alkanoyloxyalkyl" as used herein refers to R 30 -O-R31- wherein R30 is an alkanoyl group and R31 is an alkylene group. Examples of alkanoyloxyalkyl include acetoxymethyl, acetoxyethyl and the like. The term "alkenyl" as used herein refers to a straight or branched chain hydrocarbon radical containing from 2 to 15 carbon atoms and also containing at least one carbon-carbon double bond. Alkenyl groups include, for example, vinyl (ethenyl), allyl (propenyl), butenyl, 1- methyl-2-buten-1-yl and the like. The term "alkenylene" denotes a divalent group derived from a straight or branched chain hydrocarbon containing from 2 to 15 carbon atoms and also containing at least one carbon-carbon double bond. Examples of alkenylene include -CH=CH-, -CH2CH=CH-, -C(CH3)=CH-, -CH 2 CH=CHCH2-. and the like. The term "alkenyloxy" as used herein refers to an alkenyl group, as previously defined, connected to the parent molecular moiety through an oxygen (-0-) linkage. Examples of alkenyloxy include allyloxy, butenyloxy and the like. The term "alkoxy" as used herein refers to R41O- wherein R41 is a Ioweralkyl group, as defined herein. Examples of alkoxy include, but are not limited to, ethoxy, tert-butoxy, and the like. The term "alkoxyalkoxy" as used herein refers to RβoO-RβiO- wherein Rβo is Ioweralkyl as defined above and Rβι is alkylene. Representative examples of alkoxyalkoxy groups include methoxymethoxy, ethoxymethoxy, t-butoxym ethoxy and the like. The term "alkoxyalkoxyalkyl" as used herein refers to an alkoxyalkoxy group as previously defined appended to an alkyl radical. Representative examples of alkoxyalkoxyalkyl groups include methoxyethoxy ethyl, methoxymethoxymethyl, and the like. The term "alkoxyalkyi" as used herein refers to an alkoxy group as previously defined appended to an alkyl radical as previously defined. Examples of alkoxyalkyi include, but are not limited to, methoxymethyl, methoxyethyl, isopropoxymethyl and the like. The term "alkoxycarbonyl" as used herein refers to an alkoxyl group as previously defined appended to the parent molecular moiety through a carbonyl group. Examples of alkoxycarbonyl include methoxycarbonyl, ethoxycarbonyl, isopropoxycarbonyl and the like. The term "alkoxycarbonylalkenyl" as used herein refers to an alkoxycarbonyl group as previously defined appended to an alkenyl radical. Examples of alkoxycarbonylalkenyl include methoxycarbonylethenyl, ethoxycarbonylethenyl and the like. The term "alkoxycarbonylalkyl" as used herein refers to R 3 4-C(0)-R3δ- wherein R34 is an alkoxy group and R3δ is an alkylene group. Examples of alkoxycarbonylalkyl include methoxycarbonylmethyl, methoxcarbonylethyl, ethoxycarbonylmethyl and the like. The term "alkoxycarbonylaminoalkyl" as used herein refers to R 38 -C(0)-NH-R 39 - wherein R 38 is an alkoxy group and R 39 is an alkylene group. The term "alkoxycarbonyloxyalkyl" as used herein refers to R 36 -C(0)-0-R37- wherein R36 is an alkoxy group and R37 is an alkylene group. The term "(alkoxycarbonyl)thioalkoxy" as used herein refers to an alkoxycarbonyl group as previously defined appended to a thioalkoxy radical. Examples of (alkoxycarbonyl)thioalkoxy include methoxycarbonylthiomethoxy, ethoxycarbonylthiomethoxy and the like. The term "alkoxyhaloalkyl" as used herein refers to a haloalkyi radical to which is appended an alkoxy group. The terms "alkyl" and "Ioweralkyl" as used herein refer to straight or branched chain alkyl radicals containing from 1 to 15 carbon atoms including, but not limited to, methyl, ethyl, n-propyl, iso-propyl, n- butyl, iso-butyl, sec-butyl, t-butyl, n-pentyl, 1-methylbutyl, 2,2- dimethylbutyl, 2-methylpentyl, 2,2-dimethylpropyl, n-hexyl and the like. The term "(N-alkanoyl-N-alkyl)aminoalkyl" as used herein refers to R85C(0)N(R86)R87- wherein Rβ5 is an alkanoyl as previously defined, R86 is Ioweralkyl, and R87 is alkylene. The term "alkylamino" as used herein refers to R δ i NH- wherein Rδi is a Ioweralkyl group, for example, ethylamino, butylamino, and the like. The term "alkylaminoalkyP as used herein refers to a Ioweralkyl radical to which is appended an alkylamino group. The term "alkylaminocarbonyl" as used herein refers to an alkylamino group, as previously defined, appended to the parent molecular moiety through a carbonyl (-C(O)-) linkage. Examples of alkylaminocarbonyl include methylaminocarbonyl, ethylaminocarbonyl, 5 isopropylaminocarbonyl and the like. The term "alkylaminocarbonylalkenyl" as used herein refers to an alkenyl radical to which is appended an alkylaminocarbonyl group. The term "alkylaminocarbonylalkyl" as used herein refers to a Ioweralkyl radical to which is appended an alkylaminocarbonyl group. ι o The term "alkylaminocarbonylaminoalkyl" as used herein refers to R 40 -C(0)-NH-R41- wherein R40 is an alkylamino group and R 41 is an alkylene group. The term "alkylene" denotes a divalent group derived from a straight or branched chain saturated hydrocarbon having from 1 to 15 15 carbon atoms by the removal of two hydrogen atoms, for example -CH 2 -, -CH 2 CH 2 -, -CH(CH 3 )-, -CH 2 CH 2 CH 2 -, -CH 2 C(CH 3 ) 2 CH 2 - and the like. The term "alkylsulfonylamidoalkyl" as used herein refers R88S(0)2NHR89- wherein R88 is Ioweralkyl and R89 is alkylene. The term "alkylsulfonylamino" as used herein refers to an alkyl 20 group as previously defined appended to the parent molecular moiety through a sulfonylamino (-S(0)2-NH-) group. Examples of alkylsulfonylamino include methylsulfonylamino, ethylsulfonylamino, isopropylsulfonylamino and the like. The term "alkynyl" as used herein refers to a straight or branched 25 chain hydrocarbon radical containing from 2 to 15 carbon atoms and also containing at least one carbon-carbon triple bond. Examples of alkynyl include -C≡C-H, H-C≡C-CH 2 -, H-C≡C-CH(CH 3 )- and the like. The term "alkynylene" refers to a divalent group derived by the removal of two hydrogen atoms from a straight or branched chain 30 acyclic hydrocarbon group containing from 2 to 15 carbon atoms and also containing a carbon-carbon triple bond. Examples of alkynylene include -C≡C-, -C≡C-CH 2 -, -C≡C-CH(CH 3 )- and the like. The term "aminoaikyl" as used herein refers to a -NH2, alkylamino, or dialkylamino group appended to the parent molecular 35 moiety through an alkylene. The term "aminocarbonyl" as used herein refers to H2N-C(0)- . The term "aminocarbonylalkenyl" as used herein refers to an alkenyl radical to which is appended an aminocarbonyl (NH 2 C(0)-) group. The term "aminocarbonylalkoxy" as used herein refers to H2N-C(0)- appended to an alkoxy group as previously defined. Examples 5 of aminocarbonylalkoxy include aminocarbonylmethoxy, aminocarbonylethoxy and the like. The term "aminocarbonylalkyl" as used herein refers to a Ioweralkyl radical to which is appended an aminocarbonyl (NH 2 C(0)-) group. ι o The term "trialkylaminoalkyl" as used herein refers to (R90)(R91)(R92)N(R93)- wherein R90, R91, and R92 are independently selected from Ioweralkyl and R93 is alkylene. The term "aroyloxyalkyl" as used herein refers to R 3 2-C(0)-0-R 33 - wherein R32 is an aryl group and R33 is an alkylene 15 group. Examples of aroyloxyalkyl include benzoyloxymethyl, benzoyloxyethyl and the like. The term "aryl" as used herein refers to a mono- or bicyclic carbocyclic ring system having one or two aromatic rings including, but not limited to, phenyl, naphthyl, tetrahydronaphthyl, indanyl, indenyl 20 and the like. Aryl groups can be unsubstituted or substituted with one, two or three substituents independently selected from Ioweralkyl, halo, haloalkyi, haloalkoxy, hydroxyalkyi, alkenyloxy, alkoxy, alkoxyalkoxy, alkoxycarbonyl , alkoxycarbonylalkenyl, (alkoxycarbonyl)thioalkoxy , thioalkoxy, amino, alkylamino, dialkylamino, aminoaikyl, 5 trialkylaminoalkyl, aminocarbonyl, aminocarbonylalkoxy, alkanoylamino, arylalkoxy, aryloxy, mercapto, cyano, nitro, carboxaldehyde, carboxy, carboxyalkenyl, carboxyalkoxy, alkylsulfonylamino, cyanoalkoxy, (heterocyclic)alkoxy, hydroxy, hydroxalkoxy, phenyl and tetrazolylalkoxy. In addition, substituted aryl 30 groups include tetrafluorophenyl and pentafluorophenyl. The term "arylalkenyl" as used herein refers to an alkenyl radical to which is appended an aryl group, for example, phenylethenyl and the like. The term "arylalkoxy" as used herein refers to R42O- wherein R42 35 is an arylalkyi group, for example, benzyloxy, and the like. The term "arylalkoxyalkyl" as used herein refers to a Ioweralkyl radical to which is appended an arylalkoxy group, for example, benzyloxymethyl and the like. The term "arylalkyi" as used herein refers to an aryl group as 5 previously defined, appended to a Ioweralkyl radical, for example, benzyl and the like. The term "aryloxy" as used herein refers to R4 δ O- wherein R4 δ is an aryl group, for example, phenoxy, and the like. The term "arylalkylcarbonyloxyalkyl" as used herein refers to a ι o Ioweralkyl radical to which is appended an arylalkyicarbonyloxy group (i.e., R 62 C(0)0- wherein R 62 is an arylalkyi group). The term "aryloxyalkyl" refers to an aryloxy group as previously defined appended to an alkyl radical. Examples of aryloxyalkyl include phenoxymethyl, 2-phenoxyethyl and the like. 15 The term "carboxaldehyde" as used herein refers to a formaldehyde radical, -C(0)H. The term "carboxy" as used herein refers to a carboxylic acid radical, -C(0)OH. The term "carboxyalkenyl" as used herein refers to a carboxy 20 group as previously defined appended to an alkenyl radical as previously defined. Examples of carboxyalkenyl include 2-carboxyethenyl, 3- carboxy-1 -ethenyl and the like. The term "carboxyalkoxy" as used herein refers to a carboxy group as previously defined appended to an alkoxy radical as previously 25 defined. Examples of carboxyalkoxy include carboxy methoxy, carboxyethoxy and the like. The term "cyanoalkoxy" as used herein refers to an alkoxy radical as previously defined to which is appended a cyano (-CN) group. Examples of cyanoalkoxy include 3-cyanopropoxy, 4-cyanobutoxy and so the like. The term "cycloalkanoyloxyalkyl" as used herein refers to a Ioweralkyl radical to which is appended a cycloalkanoyloxy group (i.e., R 60 -C(O)-O- wherein R 60 is a cycloalkyi group). The term "cycloalkyi" as used herein refers to an aliphatic ring 35 system having 3 to 10 carbon atoms and 1 to 3 rings including, but not limited to, cyclopropyl, cyclopentyl, cyclohexyl, norbornyl, adamantyl, and the like. Cycloalkyi groups can be unsubstituted or substituted with one, two or three substituents independently selected from Ioweralkyl, haloalkyi, alkoxy, thioalkoxy, amino, alkylamino, dialkylamino, hydroxy, halo, mercapto, nitro, carboxaldehyde, carboxy, alkoxycarbonyl and carboxamide. 5 The term "cycloalkylalkyl" as used herein refers to a cycloalkyi group appended to a Ioweralkyl radical, including but not limited to cyclohexylmethyl. The term "dialkylamino" as used herein refers to R δ βR δ 7N- wherein R 6 and Rδ7 are independently selected from Ioweralkyl, for ι o example diethylamino, methyl propylamino, and the like. The term "diaikylaminoalkyl" as used herein refers to a Ioweralkyl radical to which is appended a dialkylamino group. The term "dialkylaminocarbonyl" as used herein refers to a dialkylamino group, as previously defined, appended to the parent 15 molecular moiety through a carbonyl (-C(O)-) linkage. Examples of dialkylaminocarbonyl include dimethylaminocarbonyl, diethyl aminocarbonyl and the like. The term "dialkylaminocarbonylalkenyl" as used herein refers to an alkenyl radical to which is appended a dialkylaminocarbonyl group. 20 The term "dialkylaminocarbonylalkyP as used herein refers to Rδθ-C(0)-Rδi- wherein Rδo is a dialkylamino group and R i is an alkylene group. The term "halo" or "halogen" as used herein refers to I, Br, CI or F. The term "haloalkenyl" as used herein refers to an alkenyl radical 25 to which is appended at least one halogen substituent. The term "haloalkoxy" as used herein refers to an alkoxy radical as defined above, bearing at least one halogen substituent, for example, 2-fluoroethoxy, 2,2,2-trifluoroethoxy, trifluoromethoxy, 2,2,3,3,3-pentafluoropropoxy and the like. 30 The term "haloalkoxyalkyi" as used herein refers to a Ioweralkyl radical to which is appended a haloalkoxy group. The term "haloalkyi" as used herein refers to a lower alkyl radical, as defined above, to which is appended at least one halogen substituent, for example, chloromethyl, fluoroethyl, trifluoromethyl or 35 pentafluoroethyl and the like. The term "heterocyclic ring" or "heterocyclic" or "heterocycle" as used herein refers to any 3- or 4-membered ring containing a heteroatom selected from oxygen, nitrogen and sulfur; or a 5-, 6- or 7- membered ring containing one, two or three nitrogen atoms; one oxygen atom; one sulfur atom; one nitrogen and one sulfur atom; one nitrogen and one oxygen atom; two oxygen atoms in non-adjacent positions; one 5 oxygen and one sulfur atom in non-adjacent positions; or two sulfur atoms in non-adjacent positions. The 5-membered ring has 0-2 double bonds and the 6- and 7-membered rings have 0-3 double bonds. The nitrogen heteroatoms can be optionally quaternized. The term ■ heterocyclic" also includes bicyclic groups in which any of the above ι o heterocyclic rings is fused to a benzene ring or a cyclohexane ring or another heterocyclic ring (for example, indolyl, dihydroindolyl, quinolyl, isoquinolyl, tetrahydroquinolyl, tetrahydroisoquinolyl, decahydroquinolyl, decahydroisoqumolyl, benzofuryl, dihydrobenzofuryl or benzothienyl and the like). Heterocyclics include: aziridinyl, 15 azetidinyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, pyrazolyl, pyrazolinyl, pyrazoiidinyl, imidazolyl, imidazolinyl, imidazolidinyl, pyridyl, piperidinyl, homopiperidinyl, pyrazinyl, piperazinyl, pyrimidinyl, pyridazinyl, oxazolyl, oxazolidinyl, isoxazolyl, isoxazolidinyl, morpholinyl, thiomorpholinyl, thiazolyl, thiazolidinyl, isothiazolyl, 20 isothiazolidinyl, indolyl, quinolinyl, isoquinoiinyl, benzimidazolyl, benzothiazolyl, benzoxazolyl, oxetanyl, furyl, tetrahydrofuranyl, thienyl, thiazolidinyl, isothiazolyl, triazolyl, tetrazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, pyrrolyl, pyrimidyl and benzothienyl. Heterocyclics also include compounds of the formula 25 where X * is -CH 2 - or -O- and Y * is -C(O)- or [-C(R")2-]v where R" is hydrogen or Cι-C 4 -alkyl and v is 1 , 2 or 3 such as 1 ,3-benzodioxolyl, 1 ,4-benzodioxanyl and the like. Heterocyclics also include bicyclic rings such as quinuclidinyl and the like. Heterocyclics can be unsubstituted or monosubstituted or 30 disubstituted with substituents independently selected from hydroxy, halo, oxo (=0), alkylimino (R * N= wherein R * is a Ioweralkyl group), amino, alkylamino, dialkylamino, alkoxy, alkoxyalkoxy, aminoaikyl, trialkylaminoalkyl, haloalkyi, cycloalkyi, aryl, arylalkyi, -COOH, -SO3H , alkoxycarbonyl, nitro, cyano and Ioweralkyl. In addition, nitrogen containing heterocycles can be N-protected. The term "(heterocyclic)alkoxy" as used herein refers to a heterocyclic group as defined above appended to an alkoxy radical as 5 defined above. Examples of (heterocyclic)alkoxy include 4- pyridylmethoxy, 2-pyridylmethoxy and the like. The term "(heterocyclic)alkyP as used herein refers to a heterocyclic group as defined above appended to a Ioweralkyl radical as defined above. ι o The term "heterocycliccarbonyloxyalkyl" as used herein refers to R4 6 -C(0)-0-R47- wherein R46 is a heterocyclic group and R 4 7 is an alkylene group. The term "hydroxy" as used herein refers to -OH. The term "hydroxy alkenyl" as used herein refers to an alkenyl 15 radical to which is appended a hydroxy group. The term "hydroxyalkoxy" as used herein refers to an alkoxy radical as previously defined to which is appended a hydroxy (-OH) group. Examples of hydroxyalkoxy include 3-hydroxypropoxy, 4- hydroxybutoxy and the like. 20 The term "hydroxyalkyi" as used herein refers to a Ioweralkyl radical to which is appended a hydroxy group. The term "leaving group" as used herein refers to a halide (for example, CI, Br or I) or a sulfonate (for example, mesylate, tosylate, triflate and the like). 25 The term "mercapto" as used herein refers to -SH. The terms "methylenedioxy" and "ethylenedioxy" refer to one or two carbon chains attached to the parent molecular moiety through two oxygen atoms. In the case of methylenedioxy, a fused 5 membered ring is formed. In the case of ethylenedioxy, a fused 6 membered ring is 30 formed. Methylenedixoy substituted on a phenyl ring results in the formation of a benzodioxolyl radical. c Ethylenedioxy substituted on a phenyl ring results in the formation of a benzodioxanyl heC terOm "substantially pure" as used herein means 95% or more of the specified compound. The term "tetrazolyl" as used herein refers to a radical of the formula M— - 4 »» A N or a tautomer thereof. The term "tetrazolylalkoxy" as used herein refers to a tetrazolyl radical as defined above appended to an alkoxy group as defined above. ι o Examples of tetrazolylalkoxy include tetrazolylmethoxy, tetrazolylethoxy and the like. The term "thioalkoxy" as used herein refers to R7 0 S- wherein R7 0 is Ioweralkyl. Examples of thioalkoxy include, but are not limited to, methylthio, ethylthio and the like. 15 The term "thioalkoxyalkoxy" as used herein refers to R 8 oS-R 8 ιO- wherein Rβo is Ioweralkyl as defined above and R 8 ι is alkylene. Representative examples of alkoxyalkoxy groups include CH 3 SCH 2 0-, EtSCH 2 0-, t-BuSCH 2 0- and the like. The term "thioalkoxyalkoxyalkyi" as used herein refers to a 20 thioalkoxyalkoxy group appended to an alkyl radical. Representative examples of alkoxyalkoxyalkyl groups include CH 3 SCH 2 CH 2 0CH 2 CH 2 -, CH 3 SCH 2 OCH 2 -, and the like. The term 'trans, trans" as used herein refers to the orientation of 25 substituents (R1 and R2) relative to the central substituent R as shown The term "trans, cis" as used herein refers to the orientation of substituents (R1 and R2) relative to the central substituent R as shown R ι or πι This definition encompasses both the case where R and R2 are cis and R and R1 are trans and the case where R 2 and R are trans and R and R1 are cis. The term "cis, cis" as used herein refers to the orientation of substituents (R 1 and R2) relative to the central substituent R as shown Preferred compounds of the invention are selected from the group consisting of: fraπs-frans-2-(4-Methoxphenyl)-4-(1 ,3-benzodioxol-5-yl)-1 -[3-(N- propyl-N-n-pentanesulfonylamino)propyl]-pyrrolidine-3- carboxylic acid; trans, frans-2-(4-Methoxymethoxypheny l)-4-(1 , 3-benzodioxol-5-y I)-- (2-(N-propyl-N-/7-pentanesulfonylamino)ethyl]pyrrolidine-3- carboxylic acid; trans, frans-2-(3,4-Dimethoxyphenyl)-4-(1 ,3-benzodioxol -5-yl)-1 -[2- (N-propyl-N-n-pentanesulfonylamino)ethyl]pyrrolidine-3- carboxylic acid; trans, frans-2-(3,4-Dimethoxyphenyl)-4-( 1 ,3-benzodioxol-5-yl)-1 -[2- (N-propyl-N-n-hexanesulfonylamino)ethyl]pyrrolidine-3- carboxylic acid; trans, trans-2-( 4-Propoxyphenyl)-4-(1 ,3-benzodioxol-5-yl)-1 -[2-(N- propyl-N-n-pentanesulfonylamino)ethyl]pyrrolidine-3-carboxylic acid; trans, frans-2-(3,4-Dif luorophenyl)-4-(1 ,3-benzodioxol-5-yl)-1 -(((N,N- dibutylamino)carbonyl)methyl)-pyrrolidine-3-carboxylic acid; trans, frans-2-(3,4-Dif luorophenyl)-4-( 1 , 3-benzodioxol-5-yl)- 1 -[2-(N- propyl-N-n-pentanesulfonylamino)ethyl]pyrrolidine-3-carboxylic acid; frans, frat7S-2-(3-Fluoro-4-methoxyphenyl)-4-(1 ,3-benzodioxol-5-yl)- 1 -[2-(N-propyl-N-n- hexanesulfonylamino)ethyl]pyrrolidine-3- carboxyiic acid; frans, frans-2-(3-Fluoro-4-methoxyphenyl)-4-(1 ,3-benzodioxol-5-yl)- 5 1 -(2-(N-propyl-N-(3-chloropropanesulfonyl)amino)ethyl)- pyrrolidine-3-carboxylic acid; fraπs,fra/7S-2-(3-Fluoro-4-methoxyphenyl)-4-(1 ,3-benzodioxol-5-yl)- 1 -(2-(N-isobutyl-N-(3- chloropropanesulfonyl)amino)ethyl)pyrrolidine-3-carboxylic acid; ι o frans, fra/7S-2-(3-Fluoro-4-methoxyphenyl)-4-(1 ,3-benzodioxol-5-yl)- 1 -[2-(N-propyl-N-(4- methylbutanesulfonyl)amino)ethyl]pyrrolidine-3-carboxylic acid; frans, frar.s-2-(4-Methoxy-3-fluorophenyl)-4-(7-methoxy- 1 ,3- benzodioxol-5-yl)-1 -[2-(N-propyl-N-(π- 15 pentanesulfonyl)amino)ethyl]pyrrolidine-3-carboxylic acid; trans, fraπs-2-(3-Fluoro-4-methoxyphenyl)-4-(1 ,3-benzodioxol-5-yl)- 1 -[2-(N-propyl-N-(2, 2,3,3, 3-pentafluoropropoxyethanesulfonyl)- amino)ethyl]pyrrolidine-3-carboxylic acid; trans,trans-2-C\ ,4-Benzodioxan-6-yl)-4-(7-methoxy-1 ,3-benzodioxol- 20 5-yl)- 1 -[2-(N-propyl-N-(n- pentanesulfonyl)amino)ethyl]pyrrolidine-3-carboxylic acid; frans, frans-2-(3-Fluoro-4-methoxy phenyl)-4-(1 , 3-benzodioxol-5-y I)- 1 -(2-(N-isobutyl-N-(pentanesulfonylamino)ethyl)pyrrolidine-3- carboxylic acid; 25 frans, frans-2-(3-Fluoro-4-methoxy phenyl)-4-(1 , 3-benzodioxol-5-yl)- 1 -(2-(N-(2-methoxyethyl)-N-(3-chloropropanesulfonyl)amino)- ethyl)pyrro!idine-3-carboxylic acid; trans, frans-2-(3-Fluoro-4-methoxyphenyl)-4-(1 ,3-benzodioxol-5-yl)- 1 -(2-(N-(2-methoxyethyl)-N- 30 (pentanesulfonyl)amino)ethyl)pyrrolidine-3-carboxylic acid; frans, frans-2-(3-Fluoro-4-methoxy phenyl)-4-(1 , 3-benzodioxol-5-yl)- 1 -[2-(N-propyl-N-((2,2,2-trifluoroethoxyethane)sulfonyl)amino)- ethyl]pyrrolidine-3-carboxylic acid; trans, frans-2-(3-Fluoro-4-methoxyphenyl)-4-(1 ,3-benzodioxol-5-yl)- 35 1 -(2-(N-(2-methoxyethyl)-N-(butanesulfonylamino)ethyl)- pyrrolidine-3-carboxylic acid; frans,frans-2-(3-Fluoro-4-methoxyphenyl)-4-(1 ,3-benzodioxol-5- yl)-1 -[2-(N-propyl-N-(2- methylpropanesulfonyl)amino)ethyl]pyrrolidine-3-carboxylic acid; trans, frans-2-(3-Fluoro-4-methoxyphenyl)-4-(1 ,3-benzodioxol-5-yl)- 5 1 -(2-(N-isobutyl-N-(butanesulfonylamino))ethyl)pyrrolidine-3- carboxylic acid; trans, frans-2-(2-Methylpentyl)-4-( 1 ,3-benzodioxol-5-yl)-1 -(N,N- dibutylaminocarbonylmethyl)-pyrrolidine-3-carboxylic acid; frans, frans-2-(2,2-Dimethylpentyl)-4-(1 ,3-benzodioxol-5-yl)-1 -(N,N- ι o dibutylaminocarbonylmethyl)-pyrrolidine-3-carboxylic acid; trans, frans-2-(2-(1 , 3-Dioxo-2-yl)ethyl)-4-( 1 , 3-benzodioxol-5-yl)- 1 - (N,N-dibutylaminocarbonylmethyl)-pyrrolidine-3-carboxylic acid; trans, frans-2-(2-(2-Tetrahydro-2H-pyran)ethyl)-4-(1 , 3-benzodioxol- 5-yl)-1 -(N,N-dibutylaminocarbonylmethyl)-pyrrolidine-3- 15 carboxylic acid; frans, frans-2-(2,2,4-Trimethyl-3-pentenyl)-4-(1 ,3-benzodioxol-5-yl)- 1 -(N,N-dibutylaminocarbonylmethyl)-pyrrolidine-3-carboxylic acid; trans, frans-2-(2, 2, -Dimethyl-2-(1 ,3-dioxolan-2-yl)ethyl)-4-( 1 ,3- 20 benzodioxol-5-yl)-1 -(N,N-dibutylaminocarbonylmethyl)- pyrrolidine-3-carboxylic acid; trans, frans-2-(2-(1 , 3-Dioxo-2-yl)ethyl)-4-(1 ,3-benzodioxol-5-yl)-1 - [[Λ/-4-heptyl-/V(2 methyl-3-fluorophenyl)] amino carbonylmethyl]- pyrrolidine-3-carboxylic acid; 25 frans,frans-2-(2-( 1 ,3-Dioxol-2-yt)ethyl)-4-(7-methoxy-1 ,3- benzodioxol-5-yl)-1 -(N,N-dibutylaminocarbonylmethyl)- pyrrolidine-3-carboxylic acid; trans, frans-2-((2-Methoxy phenoxy )-methyl)-4-(1 , 3-benzodioxol-5-yl)- 1 -(N,N-dibutylaminocarbonylmethyl)-pyrrolidine-3-carboxylic 30 acid; C2S,3R,4S -2-(2,2-Dimethylpentyl)-4-( 1 ,3-benzodioxol-5-yl)-1 -(N-4- heptyl-N-(4-fluoro-3-methylphenyl))aminocarbonylmethyl)- pyrrolidine-3-carboxylic acid; trans, frans-2-(2-(2-Oxopyrrolidin-1 -yl)ethyl)-4-( 1 ,3-benzodioxol-5- 35 yl)-1 -(N,N-dibutylaminocarbonylmethyl)-pyrrolidine-3-carboxylic acid; trans, frans-2-(2-( 1 ,3-Dioxol-2-yl)ethyl)-4-(7-methoxy-1 ,3- benzodioxol-5-yl)-1 -(N-4-heptyl-N-(4-fluoro-3- methylphenyl))aminocarbonylmethyl)-pyrrolidine-3-carboxylic acid; 5 trans, frans-2-(2, 2-Dimethylpentyl)-4-(7-methoxy- 1 , 3-benzodioxol-5- yl)-1 -(N,N-dibutylaminocarbonylmethyl)-pyrrolidine-3-carboxylic acid; trans, frans-2-(2, 2-dimethy lpentyl)-4-(2, 3-dihydro-benzof uran-5-yl)- 1 -(N,N-dibutylaminocarbonylmethyl)-pyrrolidine-3-carboxylic ι o acid; trans, frans-2-(2, 2, -Dimethyl-2-( 1 , 3-dioxolan-2-yl)ethy l)-4-(7- methoxy-1 ,3-benzodioxol-5-yl)-1 -(N,N- dibutylaminocarbonylmethyl)-pyrrolidine-3-carboxylic acid; trans, frans-2-(2-(2-Methoxyphenyl)-ethyl)-4-( 1 , 3-benzodioxol-5-yl)- 15 1 -(N,N-dibutylaminocarbonylmethyl)-pyrrolidine-3-carboxylic acid; frans,frans-2-(2,2-Dimethyl-3-(E -pentenyl)-4-(7-methoxy-1 ,3- benzodioxol-5-yl)-1 -(N,N-dibutyIaminocarbonylmethyl)- pyrrolidine-3-carboxylic acid; 20 trans, frans-2-(2-(2-pyridyl)ethyI)-4-(1 ,3-benzodioxol-5-y I)- 1 -(N,N- dibutylaminocarbonylmethyl)-pyrrolidine-3-carboxylic acid; (2S, 3R, 4S -2-(2-(2-oxopyrrolidin-1 -yl)ethyl)-4-(1 ,3-benzodioxol-5- yl)-1 -(N,N-dibutylaminocarbonylmethyl)-pyrrolidine-3-carboxylic acid; 25 (2S, 3R, 4S)-2-(2-(2-oxopyrrolidin-1 -yl)ethyl)-4-(1 ,3-benzodioxol-5- yl)-1 -(N-4-heptyl-N-(4-fluoro-3- methylphenyl))aminocarbonylmethyl)-pyrrolidine-3-carboxylic acid; frans,frans-2-(2-( 1 -pyrazolyl)ethyl)-4-(1 ,3-benzodioxol-5-yl)-1 -(N,N- 30 dibutylaminocarbonylmethyl)-pyrrolidine-3-carboxylic acid; trans, frans-2-(4-Methoxyphenyl)-4-(1 ,3-benzodioxol-5-y I)- 1 -[(N- butyl-N-(4-dimethylaminobutyl)amino)carbonylmethyl]- pyrrolidine-3-carboxylic acid; C2f?,3f?,4S)-2-(3-Fluoro-4-methoxyphenyl)-4-(1 ,3-benzodioxol-5-yl)1 - 35 (2-(N-propyl-N-pentanesulfonylamino)ethyl)-pyrrolidine-3- carboxylic acid; frans, frans-2-(2,2-Dimethylpentyl)-4-(1 ,3-benzodioxol-5-yl)-1 -((N- butyl-N-(4-dimethylamino)butyI)aminocarbonylmethyl)- pyrrolidine-3-carboxylic acid; trans, frans-2-(2,2-Dimethylpentyl)-4-(7-methoxy- 1 ,3-benzodioxol-5- yl)- 1 -(N-4-heptyl-N-(4-fluoro-3- methylphenyl))aminocarbonyimethyl)-pyrrolidine-3-carboxylic acid; trans, frans-2-(2,2-Dimethylpenty l)-4-(7-methoxy- 1 , 3-benzodioxol-5- yl)- 1 -((N-butyl-N-(4- dimethylamino)butyl)aminocarbonylmethyl)-pyrrolidine-3- carboxylic acid; trans, frans-2-(2,2-Dimethylpent-3-enyl)-4-( 1 ,3-benzodioxol-5-yl)- 1 - (N-4-heρtyl-N-(4-fluoro-3-methylphenyl))aminocarbonylmethyl)- pyrrolidine-3-carboxylic acid; trans, frans-2-(2,2-Dimethylpent-3-enyl)-4-(1 ,3-benzodioxol-5-yl)-1 - ((N-butyl-N-(4 dimethylamino)butyl)aminocarbonyimethyl)- pyrrolidine-3-carboxylic acid; trans, frans-2-(2,2-Dimethylpent-3-enyl)-4-(7-methoxy- 1 , 3- benzodioxol-5-yl)-1 -((N,N-dibutyl)aminocarbonylmethyl)- pyrrolidine-3-carboxylic acid; trans, frans-2-(2,2-Dimethylpent-3-enyl)-4-(7-methoxy-1 , 3- benzodioxol-5-yl)-1 -(N-4-heptyl-N-(4-fluoro-3- methylphenyl))aminocarbonylmethyl)-pyrrolidine-3-carboxylic acid; frans,frans-2-(2,2-Dimethylpent-3-enyl)-4-(7-methoxy-1 ,3- benzodioxol-5-yl)-1 -((N-butyl-N-(4- dimethylamino)butyl)aminocarbonylmethyl)-pyrrolidine-3- carboxylic acid; trans, frans-2-(2, 2, 4-Trimethyipent-3-enyl)-4-(1 ,3-benzodioxoI-5-yl)- 1 -(N-4-heptyl-N-(4-fluoro-3- methylphenyl))aminocarbonylmethyl)-pyrrolidine-3-carboxylic acid; trans, frans-2-(2, 2, 4-Trimethy lpent-3-eny l)-4-(1 , 3-benzodioxol-5-y I)- 1 -((N-butyl-N-(4-dimethylamino)butyl)aminocarbonylmethyl)- pyrrolidine-3-carboxylic acid; trans,trans-2-(2, 2, 4-Trimethylpent-3-enyl)-4-(7-methoxy- 1 ,3- benzodioxol-5-yl)-1 -((N,N-dibutyl)aminocarbonylmethyl)- yrrolidine-3-carboxylic acid; trans, frans-2-(2, 2, 4-Trimethylpent-3-enyl)-4-(7-methoxy- 1 ,3- 5 benzodioxol-5-yl)- 1 -(N-4-heptyl-N-(4-fluoro-3- methylphenyl))aminocarbonylmethyl)-pyrrolidine-3-carboxylic acid; trans, frans-2-(2, 2, 4-Trimethylpent-3-enyl)-4-(7-methoxy- 1 ,3- benzodioxol-5-yl)-1 -((N-butyl-N-(4- ι o dimethy lamino)butyl)aminocarbonylmethyl)-pyrrolidine-3- carboxylic acid; trans, frans-2-(2-(1 ,3-Dioxol-2-yl)ethyl)-4-(1 ,3-benzodioxol-5-yl)-1 [(N-butyl-N-(4-dimethylaminobutyl)amino)carbonylmethyl]- pyrrolidine-3-carboxylic acid; 15 trans, frans-2-(2-(1 ,3-Dioxol-2-yl)ethyl)-4-(7-methoxy-1 ,3- benzodioxol-5-yl)-1 -[(N-butyl-N-(4- dimethylaminobutyl)amino)carbonylmethyl]-pyrrolidine-3- carboxylic acid; trans, frans-2-(2, 2, -Dimethy l-2-(1 ,3-Dioxol-2-yl)ethyl)-4-(1 , 3- 20 benzodioxol-5-yl)- 1 -(N-4-heptyl-N-(4-fluoro-3- methylphenyl))aminocarbonylmethyl)-pyrrolidine-3-carboxylic acid; frans, frans-2-(2,2-Dimethyl-2-(1 ,3-dioxolan-2-yl)ethyl)-4-( 1 ,3- benzodioxol-5-yl)-1 -[(N-butyl-N-(4- 25 dimethylaminobutyl)amino)carbonylmethyl]-pyrrolidine-3- carboxylic acid; trans, frans-2-(2, 2, -Dimethy l-2-(1 , 3-Dioxol-2-yl)ethyl)-4-(7- methoxy-1 ,3-benzodioxol-5-yl)-1 -(N-4-heptyl-N-(4-fluoro-3- methylphenyl))aminocarbonylmethyl)-pyrrolidine-3-carboxylic 30 acid; trans, frans-2-(2 , 2-Dimethyl-2-( 1 ,3-dioxolan-2-y l)ethyl)-4-(7- methoxy- 1 ,3-benzodioxol-5-yl)-1 -[(N-butyl-N-(4- dimethylaminobutyl)amino)carbonylmethyl]-pyrrolidine-3- carboxylic acid; frans,frans-2-(2-(2-Methoxyphenyl)-ethyl)-4-(1 ,3-benzodioxol-5-yl)- 1 -(N-4-heptyl-N-(4-fluoro-3- methylphenyl))amino)carbonylmethyl]-pyrrolidine-3-carboxylic acid; 5 frans,frans-2-(2-(2-Methoxyphenyl)-ethyl)-4-(1 ,3-benzodioxol-5-yl)- 1 -[(N-butyl-N-(4-dimethylaminobutyl)amino)carbonylmethyl]- pyrrolidine-3-carboxylic acid; trans, frans-2-(2-(2-Methoxyphenyl)-ethyl)-4-(7-methoxy-1 , 3- benzodioxol-5-yl)-1 -[((N,N-dibutyl)amino)carbonylmethyl]- ι o pyrrolidine-3-carboxylic acid; trans, frans-2-(2-(2-Methoxyphenyl)-ethyl)-4-(7-methoxy-1 , 3- benzodioxol-5-yl)-1 -(N-4-heptyl-N-(4-fluoro-3- methylphenyl))amino)carbonylmethyl]-pyrrolidine-3-carboxylic acid; 15 trans, frans-2-(2-(2-MethoxyphenyI)-ethyl)-4-(7-methcxy-1 , 3- benzodioxol-5-yl)-1 -[(N-butyl-N-(4- dimethylaminobutyl)amino)carbonylmethyl]-pyrrolidine-3- carboxylic acid; trans, frans-2-((2-Methoxyphenoxy)-methyl)-4-(1 ,3-benzodioxol-5-yl)- 20 1 -(N-4-heptyl-N-(4-fluoro-3- methylphenyl))amino)carbonylmethyl]-pyrrolidine-3-carboxylic acid; trans, frans-2-((2-Methoxyphenoxy)-methyl)-4-( 1 ,3-benzodioxol-5-yl)- 1 -[(N-butyl-N-(4-dimethylaminobutyl)amino)carbonylmethyl]- 25 pyrrolidine-3-carboxylic acid; trans, frans-2-((2-Methoxyphenoxy)-methyI)-4-(7-methoxy- 1 ,3- benzodioxol-5-yl)-1 -[((N,N-dibutyl)amino)carbonylmethyl]- pyrrolidine-3-carboxyIic acid; frans,frans-2-((2-Methoxyphenoxy)-methyl)-4-(7-methoxy-1 ,3- 30 benzodioxol-5-yl)-1 -(N-4-heptyl-N-(4-fluoro-3- methylphenyl))amino)carbonylmethyl]-pyrrolidine-3-carboxylic acid; trans, frans-2-(2-(2-Methoxyphenoxy)-methyl)-4-(7-methoxy- 1 ,3- benzodioxol-5-yl)-1 -[(N-butyl-N-(4- 35 dimethylaminobutyl)amino)carbonylmethyl]-pyrrolidine-3- carboxylic acid; frans,frans-2-(2-(2-Oxo 1 ,2-dihydro pyridin-1-yl)-ethyl)-4-(1 ,3- benzodioxol-5-yl)-1 -[((N,N-dibutyl)amino)carbonylmethyl]- pyrrolidine-3-carboxylic acid; trans, frans-2-(2-(2-Oxopyridin-1 -yl)-ethyl)-4-(1 ,3-benzodioxol-5- 5 yl)- 1 -[(N-4-heptyl-N-(4-fluoro-3- methylphenyl)amino)carbonylmethyl]-pyrroIidine-3-carboxylic acid; trans, frans-2-(2-(2-Oxopy ridin-1 -y l)-ethyl)-4-(1 , 3-benzodioxol-5- yl)-1 -[(N-butyl-N-(4-dimethylaminobutyl)amino)carbonylmethyl]" ι o pyrrolidine-3-carboxylic acid; trans, frans-2-(2-(2-Oxopyridin-1 -yl)-ethyl)-4-(7-methoxy-1 ,3- benzodioxol-5-yl)-1 -[((N,N-dibutyl)amino)carbonylmethyl]- pyrrolidine-3-carboxylic acid; frans,frans-2-(2-(2-Oxopyridin-1 -yl)-ethyl)-4-(7-methoxy-1 ,3- 15 benzodioxol-5-yl)-1 -[(N-4-heptyl-N-(4-fluoro-3- methylphenyl)amino)carbonylmethyl]-pyrrolidine-3-carboxylic acid; trans, frans-2-(2-(2-Oxopyridin-1 -yl)-ethyl)-4-(7-methoxy-1 ,3- benzodioxol-5-yl)-1 -[(N-butyl-N-(4- 20 dimethylaminobutyl)amino)carbonyimethyl]-pyrrolidine-3- carboxylic acid; trans, frans-2-(2(-2-Oxopiperidin- 1 -yl)-ethy I )-4-(1 , 3-benzodioxol-5- yl)-1 -[((N,N-dibutyl)amino)carbonylmethyl]-pyrrolidine-3- carboxylic acid; 25 trans, frans-2-(2-(2-Oxopiperidin- 1 -yl)-ethyl)-4-(1 ,3-benzodioxol-5- yl)- 1 -[(N-4-heptyl-N-(4-fluoro-3- methylphenyl)amino)carbonylmethyl]-pyrrolidine-3-carboxylic acid; trans, frans-2-(2-(2-Oxopiperidin-1 -yl)-ethyl)-4-(7-methoxy- 1 ,3- 30 benzodioxol-5-yl)-1 -[((N,N-dibutyl)amino)carbonylmethyl]- pyrrolidine-3-carboxylic acid; trans, frans-2-(2-(2-Oxopiperidin-1 -yl)-ethyl)-4-(7-methoxy- 1 ,3- benzodioxol-5-yl)-1 -[((N,N-dibutyl)amino)carbonylmethyl]- pyrrolidine-3-carboxylic acid; 35 frans,frans-2-(2-(2-Oxopiperidin-1 -yl)-ethyl)-4-(7-methoxy-1 ,3- benzodioxol-5-yl)- 1 -[(N-4-heptyl-N-(4-fluoro-3- methylphenyl)amino)carbonylmethyl]-pyrrolidine-3-carboxylic acid; trans, frans-2-(2-(2-Oxopiperidin-1 -yl)-ethyl)-4-(7-methoxy- 1 ,3- benzodioxol-5-yl)-1 -[(N-butyl-N-(4- dimethylaminobutyl)amino)carbonylmethyl]-pyrrolidine-3- carboxylic acid; trans, frans-2-(2-(2-Oxopy rrolidin-1 -y l)ethyl)-4-(1 , 3-benzodioxol-5- yl)-1 -[(N-butyl-N-(3-hydroxypropyl)amino)carbonylmethyl]- pyrrolidine-3-carboxylic acid; trans, frans-2-(2-(2-Oxopy rroli din- 1 -yl)ethyl)-4-(1 ,3-benzodioxol-5- yl)-1 -[(N-butyl-N-(propoxy)amino)carbonylmethyl]-pyrrolidine-3- carboxylic acid; trans, frans-2-(2-(2-Oxopyrrolidin-1 -yl)ethyl)-4-(1 ,3-benzodioxol-5- yl)-1 -[(N-butyl-N-(4 dimethylaminobutyl)amino)carbonylmethyl]- pyrrolidine-3-carboxylic acid; frans, frans-2-(2-(2-Oxopyrro!idin-1 -yl)ethyl)-4-( 1 ,3-benzodioxol-5- yl)- 1 -[(N-butyl-N-(4- trimethylammoniobutyl)amino)carbonylmethyl]-pyrrolidine-3- carboxylic acid; trans, frans-2-(2-(2-Oxopyrrolidin-1 -yl)ethy I) -4-(7-methoxy-1 , 3- benzodioxol-5-yl)-1 -(N,N-dibutylaminocarbonylmethyl)- pyrrolidine-3-carboxylic acid; trans, frans-2-(2-(2-Oxopyrrolidin-1 -y I )ethyl)-4-(7-methoxy- 1 ,3- benzodioxol-5-yl)-1 -[(N-butyl-N-(3- hydroxypropyl)amino)carbonylmethyl]-pyrrolidine-3-carboxylic acid; trans, frans-2-(2-(2-Oxopyrrolidin-1 -yl)ethyl)-4-(7-methoxy- 1 , 3- benzodioxol-5-yl)-1 -[(N-4-heptyl-N-(4-fluoro-3- methylphenyl)amino)carbonylmethyl]-pyrrolidine-3-carboxylic acid; trans, frans-2-(2-(2-Oxopyrrolidin-1 -yl)ethyl)-4-(7-methoxy-1 , 3- benzodioxol-5-yl)-1 -[(N-butyl-N- (propoxy)amino)carbonylmethyl]-pyrrolidine-3-carboxylic acid; trans, frans-2-(2-(2-Oxopyrrolidin-1 -y I )ethyl)-4-(7-methoxy- 1 ,3- benzodioxol-5-yl)-1 -[(N-butyl-N-(4- dimethylaminobutyl)amino)carbonylmethyl]-pyrrolidine-3- carboxylic acid; frans,frans-2-(2-(2-Oxopyrrolidin-1 -yl)ethyl)-4-(7-methoxy-1 ,3- benzodioxol-5-yl)-1 -[(N-butyl-N-(4- trimethylammoniobutyl)amino)carbonylmethyl]-pyrrolidine-3- carboxylic acid; 5 trans, frans-2-(2-(2-Oxopy rrolidin-1 -y l)ethyl)-4-(2, 3-dihydro- benzofuran-5-yl)-1 -(N,N-dibutylaminocarbonylmethyl)- pyrrolidine-3-carboxylic acid; trans, frans-2-(2-(2-Oxopy rrolidin-1 -y l)ethyl)-4-(2, 3-dihydro- benzofuran-5-yl)-1 -[(N-4-heptyl-N-(4-fluoro-3- ι o methylphenyl)amino)carbonylmethyl]-pyrrolidine-3-carboxylic acid; trans, frans-2-(2-(2-Oxopyrrolidin-1 -yl)ethyl)-4-(2, 3-d ihydro- benzofuran-5-yl)-1 -[(N-butyl-N-(4- dimethylaminobutyl)amino)carbonylmethyl]-pyrrolidine-3- 15 carboxylic acid; trans, frans-2-(2-(3,3-Dimethyl-2-oxopyrrolidin-1 -yl)ethyl)-4-( 1 , 3- benzodioxol-5-yl)-1 -(N,N-dibutylaminocarbonylmethyl)- yrrolidine-3-carboxylic acid; trans, frans-2-(2-(3,3-Dimethyl-2-oxopyrrolidin-1 -yl)ethyl)-4-( 1 ,3- 20 benzodioxol-5-yl)-1 -[(N-4-heptyl-N-(4-fluoro-3- methylphenyl)amino)carbonylmethyl]-pyrrolidine-3-carboxylic acid; trans, frans-2-(2-(3,3-Dimethyl-2-oxopyrrolidin- 1 -yl)ethyl)-4-(1 ,3- benzodioxol-5-yl)-1 -[(N-butyl-N-(4- 25 dimethylaminobutyl)amino)carbonylmethyl]-pyrrolidine-3- carboxylic acid; trans, frans-2-(2-(4,4-Dimethyl-2-oxopyrrolidin-1 -yl)ethyl)-4-( 1 ,3- benzodioxol-5-yl)-1 -(N,N-dibutylaminocarbonylmethyl)- pyrrolidine-3-carboxylic acid; 30 trans, frans-2-(2-(4,4-Dimethyl-2-oxopyrrolidin-1 -yl)ethyl)-4-( 1 ,3- benzodioxol-5-yl)-1 -[(N-4-heptyl-N-(4-fluoro-3- methylphenyl)amino)carbonylmethyl]-pyrrolidine-3-carboxylic acid; trans, frans-2-(2-(4, 4- Dimethy l-2-oxopyrrolidin-1 -yl)ethyl)-4-( 1 ,3- 35 benzodioxoi-5-yl)-1 -[(N-butyl-N-(4- dimethylaminobutyl)amino)carbonylmethyl]-pyrrolidine-3- carboxylic acid; frans,frans-2-(2-(1 -propanesultamyl)ethyl)-4-(1 ,3-benzodioxol-5-yl)- 1 -(N,N-dibutylaminocarbonylmethyl)-pyrrolidine-3-carboxylic acid; trans, frans-2-(2-(1 -propanesultamyl)ethyl)-4-(1 ,3-benzodioxol-5-y I)- 5 1 -[(N-4-heptyl-N-(4-fluoro-3- methylphenyl)amino)carbonylmethyl]-pyrrolidine-3-carboxylic acid; frans,frans-2-(2-(1 -propanesultamyl)ethyl)-4-(1 ,3-benzodioxol-5-yl)- 1 -[(N-butyl-N-(3-hydroxypropyl)amino)carbonylmethylj- ι o pyrrolidine-3-carboxylic acid; frans,frans-2-(2-(1 -propanesultamyl)ethyl)-4-(1 ,3-benzodioxol-5-yl)- 1 -[(N-butyl-N-(propoxy)amino)carbonylmethyl]-pyrrolidine-3- carboxylic acid; trans, frans-2-(2-( 1 -propanesultamyI)ethyl)-4-(1 ,3-benzodioxol-5-yl)- 15 1 -[(N-butyl-N-(4 dimethylaminobutyl)amino)carbonyimethyl]- pyrrolidine-3-carboxylic acid; trans, frans-2-(2-(1 -propanesultamyl)ethyl)-4-(7-methoxy-1 ,3- benzodioxol-5-yl)-1 -(N,N-dibutylaminocarbonylmethyl)- pyrrolidine-3-carboxylic acid; 20 trans, frans-2-(2-(1 -propanesultamyl)ethyl)-4-(7-methoxy-1 , 3- benzodioxol-5-yl)-1 -[(N-4-heptyl-N-(4-fluoro-3- methylphenyl)amino)carbonylmethyl]-pyrrolidine-3-carboxylic acid; trans, frans-2-(2-(1 -propanesultamyl)ethyl)-4-(7-methoxy-1 ,3- 25 benzodioxol-5-yl)-1 -[(N-butyl-N-(4- dimethylaminobutyl)amino)carbonylmethyl]-pyrrolidine-3- carboxylic acid; trans, frans-2-(2-(1 -propanesultamy l)ethyl)-4-(2, 3-di hydro- benzofuran-5-yl)-1 -(N,N-dibutylaminocarbonylmethyl)- 30 pyrrolidine-3-carboxylic acid; trans, frans-2-(2-(1 -propanesultamyl)ethyl)-4-(2, 3-di hyd ro- benzofuran-5-yl)-1 -[(N-4-heptyl-N-(4-f!uoro-3- methylphenyl)amino)carbonylmethyl]-pyrrolidine-3-carboxylic acid; frans,frans-2-(2-(1 -propanesultamyl)ethyl)-4-(2,3-dihydro- benzofuran-5-yl)-1 -[(N-butyl-N-(4- dimethylaminobutyl)amino)carbonylmethyl]-pyrrolidine-3- carboxylic acid; frans,frans-2-(2-(1 -pyrazoly l)ethyl)-4-( 1 , 3-benzodioxol-5-yl)- 1 -[(N- 4-heptyl-N-(4-fluoro-3-methylphenyl)amino)carbonylmethylj- pyrrolidine-3-carboxylic acid; frans,frans-2-(2-(1 -pyrazoly l)ethyl)-4-(1 , 3-benzodioxol-5-yl)-1 -[(N- butyl-N-(3-hydroxypropyl)amino)carbonylmethyl]-pyrrolidine-3- carboxylic acid; trans, frans-2-(2-(1 -pyrazoly l)ethyl)-4-(1 , 3-benzodioxol-5-yl)-1 -(N- butyl-N-(propoxy)amino)carbonylmethyl]-pyrrolidine-3- carboxylic acid; trans, frans-2-(2-(1 -pyrazoly l)ethyl)-4-(1 , 3-benzodioxol-5-yl)- 1 -[(N- butyl-N-(4-dimethylaminobutyl)amino)carbonylmethyl]- pyrrolidine-3-carboxylic acid; trans, frans-2-(2-(1 -py razolyl)ethy l)-4-(7-methoxy- 1 , 3-benzodioxol- 5-yl)-1 -(N,N-dibutylaminocarbonylmethyl)-pyrrolidine-3- carboxylic acid; frans,frans-2-(2-(1 -pyrazolyl)ethyl)-4-(7-methoxy-1 ,3-benzodioxol- 5-yl)- 1 -[(N-4-heptyl-N-(4-fluoro-3- methylphenyl)amino)carbonyimethyl]-pyrrolidine-3-carboxylic acid; trans, frans-2-(2-(1 -pyrazoly I) ethyl)-4-(7-methoxy- 1 ,3-benzodioxol- 5-yl)- 1 -[(N-butyl-N-(4- dimethylaminobutyl)amino)carbonyimethyl]-pyrrolidine-3- carboxylic acid; trans, frans-2-(2-(1 -py razolyl)ethy l)-4-(2,3-dihy dro-benzof uran-5- yl)-1-(N,N-dibutylaminocarbonylmethyl)-pyrrolidine-3-carboxylic acid; trans, frans-2-(2-(1 -pyrazoly I )ethyl)-4-(2, 3-dihydro-benzof uran-5- yl)- 1 -[(N-4-heptyl-N-(4-fluoro-3- methylphenyl)amino)carbonylmethyl]-pyrrolidine-3-carboxylic acid; trans, frans-2-(2-(1 -pyrazoly l)ethyl)-4-(2, 3-dihydro-benzof uran-5- yl)-1 -[(N-butyl-N-(4-dimethylaminobutyl)amino)carbonylmethyl]- pyrrolidine-3-carboxylic acid; frans,frans-2-(2-(2-oxazolyl)ethyl)-4-(1 ,3-benzodioxol-5-yl)- 1 -(N,N- dibutylaminocarbonylmethyl)-pyrrolidine-3-carboxyiic acid; trans, frans-2-(2-(Oxazol-2-y l)ethyl)-4-(1 , 3-benzodioxol-5-yl)- 1 -[(N- 4-heptyl-N-(4-fluoro-3-methylphenyl)amino)carbonylmethyl]- pyrrolidine-3-carboxylic acid; trans, frans-2-(2-(Oxazol-2-y l)ethyl)-4-(1 , 3-benzodioxol-5-yl)-1 -[(N- butyl-N-(3-hydroxypropyl)amino)carbonylmethyl]-pyrrolidine-3- carboxylic acid; frans, frans-2-(2-(Oxazol-2-yl)ethyl)-4-(1 ,3-benzodioxol-5-yl)-1 -[(N- butyl-N-(propoxy)amino)carbonylmethyl]-pyrrolidine-3- carboxylic acid; frans,frans-2-(2-(Oxazol-2-yl)ethyl)-4-(1 ,3-benzodioxol-5-yl)-1 -[(N- butyl-N-(4-dimethylaminobutyl)amino)carbonylmethyl]- pyrrolidine-3-carboxylic acid; trans, frans-2-(2-(Oxazol-2-yl)ethyl)-4-(7-methoxy-1 ,3-benzodioxol- 5-yl)-1 -(N,N-dibutylaminocarbonylmethyl)-pyrrolidine-3- carboxylic acid; trans, frans-2-(2-(Oxazol-2-yl)ethyl)-4-(7-methoxy-1 ,3-benzodioxol- 5-yl)- 1 -[(N-4-heptyl-N-(4-fluoro-3- methylphenyl)amino)carbonylmethyI]-pyrrolidine-3-carboxylic acid; trans, frans-2-(2-(Oxazol-2-yl)ethyl)-4-(7-methoxy-1 ,3-benzodioxol- 5-yl)- 1 -[(N-butyl-N-(4- dimethylaminobutyl)amino)carbonylmethyl]-pyrrolidine-3- carboxylic acid; frans,fraπs-2-(2-(5-Methyloxazol-2-yl)ethyl)-4-( 1 ,3-benzodioxol-5- yl)-1 -(N,N-dibutylaminocarbonylmethyl)-pyrrolidine-3-carboxylic acid; trans, frans-2-(2-(5-Methyloxazol-2-yl)ethyl)-4-( 1 ,3-benzodioxol-5- yl)- 1 -[(N-4-heptyl-N-(4-fluoro-3- methylphenyl)amino)carbonylmethyl]-pyrrolidine-3-carboxylic acid; frans, frans-2-(2-(5-Methyloxazol-2-yl)ethyl)-4-( 1 ,3-benzodioxol-5- yl)-1 -[(N-butyl-N-(4-dimethylaminobutyl)amino)carbonylmethyl]- pyrrolidine-3-carboxylic acid; frans,frans-2-(2-(2,5-Dioxopyrrolidin-1 -yl)ethyl)-4-(1 ,3-benzodioxol- 5-yl)-1 -(N,N-dibutylaminocarbonylmethyl)-pyrrolidine-3- carboxylic acid; trans, frans-2-(2-(2,5-Dioxopyrrolidin-1 -yl)ethyl)-4-(1 ,3-benzodioxol- 5 5-yl)- 1 -[(N-4-heptyl-N-(4-fluoro-3- methylphenyl)amino)carbonylmethyl]-pyrrolidine-3-carboxylic acid; trans, frans-2-(2-(2, 5-Dioxopy rrolidin-1 -yl)ethyl)-4-(1 , 3-benzodioxol- 5-yl)-1 -[(N-butyl-N-(3-hydroxypropyl)amino)carbonylmethyl]- ι o pyrrolidine-3-carboxylic acid; trans, frans-2-(2-(2, 5-Dioxopy rrolidin-1 -yl)ethyl)-4-(1 , 3-benzodioxol- 5-yl)-1 -[(N-butyl-N-(propoxy)amino)carbonylmethyl]-pyrrolidine- 3-carboxylic acid; trans, frans-2-(2-(2, 5-Dioxopy rrolidin-1 -yl)ethyl)-4-(1 , 3-benzodioxol- 15 5-yl)- 1 -[(N-butyl-N-(4-dimethylaminobutyl) amino)carbonylmethyl]-pyrrolidine-3-carboxylic acid; frans,frans-2-(2-(2,5-Dioxopyrrolidin-1 -yl)ethyl)-4-(7-methoxy-1 ,3- benzodioxol-5-yl)-1 -(N,N-dibutylaminocarbonylmethyl)- pyrrolidine-3-carboxylic acid; 0 trans, frans-2-(2-(2,5-Dioxopyrrolidin-1 -yl)ethyl)-4-(7-methoxy-1 , 3- benzodioxol-5-yl)- 1 -[(N-4-heptyl-N-(4-fluoro-3- methylphenyl)amino)carbonylmethyl]-pyrrolidine-3-carboxylic acid; trans, frans-2-(2-(Pyridin-2-yl)ethyl)-4-( 1 ,3-benzodioxol-5-yl)-1 -[(N- 25 4-heptyl-N-(4-fluoro-3-methylphenyl)amino)carbonylmethyl]- pyrrolidine-3-carboxylic acid; trans, frans-2-(2-(Py ridin-2-yl)ethy l)-4-( 1 , 3-benzodioxol-5-yl)-1 -[(N- butyl-N-(3-hydroxypropyl)amino)carbonylmethyl]-pyrrolidine-3- carboxyiic acid; 30 trans, frans-2-(2-(Pyridin-2-y I )ethy I )-4-( 1 , 3-benzodioxol-5-y l)-1 -[( N- butyl-N-(propoxy)amino)carbonylmethyl]-pyrrolidine-3- carboxylic acid; trans, frans-2-(2-(Pyridin-2-yl)ethyl)-4-( 1 ,3-benzodioxol-5-yl)-1 -[(N- butyl-N-(4-dimethylaminobutyl)amino)carbonylmethyl]- 35 pyrrolidine-3-carboxylic acid; frans,frans-2-(2-(Pyridin-2-yl)ethyl)-4-(7-methoxy-1 ,3-benzodioxol- 5-yl)-1 -(N,N-dibutylaminocarbonylmethyl)-pyrrolidine-3- carboxylic acid; trans, frans-2-(2-(Pyridin-2-yl)ethyl)-4-(7-methoxy-1 ,3-benzodioxol- 5 5-yl)- 1 -[(N-4-heptyl-N-(4-fluoro-3- methylphenyl)amino)carbonylmethyl]-pyrrolidine-3-carboxylic acid; frans,frans-2-(2-(Pyridin-2-yl)ethyl)-4-(7-methoxy-1 ,3-benzodioxol- 5-yl)- 1 -[(N-butyl-N-(4- ι o dimethy laminobutyl)amino)carbony I methyl]-py rrolidine-3- carboxylic acid; trans, frans-2-(2-(Py rimidin-2-y l)ethyl)-4-( 1 , 3-benzodioxol-5-yl)- 1 - (N,N-dibutylaminocarbonylmethyl)-pyrrolidine-3-carboxylic acid; frans,frans-2-(2-(Pyrimidin-2-yl)ethyl)-4-( 1 ,3-benzodioxol-5-yl)-1 - 15 [(N-4-heptyl-N-(4-fluoro-3- methylphenyl)amino)carbonylmethyl]-pyrrolidine-3-carboxylic acid; trans, frans-2-(2-(Py rimidin-2-y l)ethyl)-4-(1 , 3-benzodioxol-5-yl)- 1 - [(N-butyl-N-(4-dimethylaminobutyl)amino)carbonylmethylj- 20 pyrrolidine-3-carboxylic acid; trans, frans-2-(2-( 1 , 3-benzodioxol-4-y l)ethyl)-4-(1 , 3-benzodioxol-5- yl)-1 -(N,N-dibutylaminocarbonylmethyl)-pyrrolidine-3-carboxylic acid; trans, frans-2-(2-(1 ,3-benzodioxol-4-yl)ethyl)-4-(1 ,3-benzodioxol- 5- 25 yl)- 1 -[(N-4-heptyl-N-(4-fluoro-3- methylphenyl)amino)carbonylmethyl]-pyrrolidine-3-carboxylic acid; and frans, frans-2-(2-(1 , 3-benzodioxol-4-yl)ethyl)-4-(1 ,3-benzodioxol-5- yl)-1-[(N-butyl-N-(4 dimethylaminobutyl)amino)carbonylmethyl]- 30 pyrrolidine-3-carboxylic acid; or a pharmaceutically acceptable salt. Most preferred compounds: of the invention are selected from the group consisting of: 35 trans, frans-2-(2-( 1 , 3-Dioxol-2-yl)ethyl)-4-( 1 , 3-benzodioxol-5-yl)- 1 - (N,N-dibutylaminocarbonylmethyl)-pyrrolidine-3-carboxylic acid; frans,frans-2-(2,2,-Dimethyl-2-(1 ,3-dioxolan-2-yl)ethyl)-4-( 1 ,3- benzod\oxo\-b-y\)-Λ ~(N,N-dibυtylaminocarbonylmethyl)- pyrrolidine-3-carboxylic acid; frans, frans-2-(2-(1 , 3-Dioxol-2-yl)ethyl)-4-( 1 ,3-benzodioxol-5-yl)- [[N-4-heptyl-N-(2-methyl-3-fluorophenyI)] aminocarbonylmethyl]-pyrrolidine-3-carboxylic acid; trans, frans-2-(2-(1 ,3-Dioxol-2-yl)ethyl)-4-(7-methoxy-1 ,3- benzodioxol-5-yl)-1-(N,N-dibutylaminocarbonyimethyl)- pyrrolidine-3-carboxylic acid; frans,frans-2-((2-Methoxyphenoxy)-methyl)-4-( 1 ,3-benzodioxol-5-yl)- 1 -(N,N-dibutylaminocarbonylmethyl)-pyrrolidine-3-carboxylic acid; trans, frans-2-(2-(2-Oxopy rrolidin-1 -y l)ethyl)-4-(1 , 3-benzodioxol-5- yl)-1 -(N,N-dibutylaminocarbonylmethyl)-pyrrolidine-3-carboxylic acid; trans, frans-2-(2-( 1 ,3-Dioxol-2-yl)ethyl)-4-(7-methoxy-1 ,3- benzodioxol-5-yl)-1 -(N-4-heptyl-N-(4-fluoro-3- methylphenyl))aminocarbonylmethyl)-pyrrolidine-3-carboxylic acid; frans,frans-2-(2,2-Dimethylpentyl)-4-(7-methoxy- 1 ,3-benzodioxol-5- yl)-1 -(N,N-dibutylaminocarbonylmethyl)-pyrrolidine-3-carboxylic acid; trans, frans-2-(2, 2, -Dimethy l-2-(1 , 3-dioxolan-2-yl)ethy l)-4-(7- methoxy-1 ,3-benzodioxol-5-yl)-1 -(N,N- dibutylaminocarbonylmethyl)-pyrrolidine-3-carboxylic acid; trans, frans-2-(2-(2-Methoxyphenyl)-ethy l)-4-(1 , 3-benzodioxol-5-yl)- 1 -(N,N-dibutylaminocarbonylmethyl)-pyrrolidine-3-carboxylic acid; frans, frans-2-(2,2-Dimethyl-3-(E)-pentenyl)-4-(7-methoxy- 1 ,3- benzodioxol-5-yl)-1 -(N,N-dibutylaminocarbonylmethyl)- pyrrolidine-3-carboxylic acid; frans, frans-2-(2-(2-pyridyl)ethyl)-4-( 1 ,3-benzodioxol-5-y I)- 1 -(N,N- dibutylaminocarbonylmethyl)-pyrrolidine-3-carboxylic acid; (2S, 3R, 4S)-2-(2-(2-oxopyrrolidin-1 -yl)ethyl)-4-(1 ,3-benzodioxol-5- yl)-1 -(N,N-dibutylaminocarbonylmethyl)-pyrrolidine-3- carboxylicacid; (2S, 3R, 4S)-2-(2-(2-oxopyrrolidin-1 -yl)ethyl)-4-(1 ,3-benzodioxol-5- yl)-1 -(N-4-heptyl-N-(4-fluoro-3- methylphenyl))aminocarbonylmethyl)-pyrrolidine-3-carboxylic acid; trans, frans-2-(2-(1 -pyrazolyl)ethyl)-4-(1 ,3-benzodioxol-5-yl)-1 -(N,N- dibutylaminocarbonylmethyl)-pyrrolidine-3-carboxylic acid; and (2S, 3R, 4S)-2-(3-Fluoro-4-methoxyphenyl)-4-(1 ,3-benzodioxol-5-yl)- 1 -[((N-propyl-N-pentanesulfonyl)amino)ethyl]-pyrrolidine-3- carboxyiic acid; or a pharmaceutically acceptable salt thereof. Methods for preparing the compounds of the invention are shown in Schemes l-XV. Scheme I illustrates the general procedure for preparing the compounds of the invention when n and m are 0, Z is -CH2- and W is -CO2H. A β-ketoester 1, where E is Ioweralkyl or a carboxy protecting group is reacted with a nitro vinyl compound , in the presence of a base (for example, 1 ,8-diazabicyclo[5.4.0]undec-7-ene (DBU) or sodium ethoxide or sodium hydride and the like) in an inert solvent such as toluene, benzene, tetrahydrofuran or ethanol and the like. The condensation product 3_ is reduced (for example, hydrogenation using a Raney nickel or platinum catalyst). The resulting amine cyclizes to give the dihydro pyrrole 4. Reduction of 4 (for example, sodium cyanoborohydride or catalytic hydrogenation and the like) in a protic solvent such as ethanol or methanol and the like gives the pyrrolidine compound 5_ as a mixture of cis-cis, trans, trans and cis, trans products. Chromatographic separation removes the cis-cis isomer leaving a mixture of the trans, trans and cis, trans isomers which is further elaborated. The cis-cis isomer can be epimerized (for example, using sodium ethoxide in ethanol) to give the trans, trans isomer and then carried on as described below. The pyrrolidine nitrogen is (1) acylated or sulfonylated with R3-X (R3 is R4-C(0)- or Rβ-S(0)2- and X is a leaving group such as a halide (CI is preferred) or X taken together with R4-C(0)- or R 6 -S(0)2- forms an activated ester including esters or anhydrides derived from formic acid, acetic acid and the like, alkoxycarbonyl halides, N-hydroxysuccinimide, N-hydroxyphthaiimide, N-hydroxybenzotriazole, N-hydroxy-5-norbornene-2,3-dicarboxamide, 2,4,5-trichlorophenol and the like) or (2) alkylated with R3-X where X is a leaving group (for example, X is a halide (for example, CI, Br or I) or X is a leaving group such as a sulfonate (for example, mesylate, tosylate, triflate and the like)) in the presence of a base such as diisopropyl ethylamine or triethylamine and the like to give the N- derivatized pyrrolidine 6_ which is still a mixture of trans, trans and cis.trans isomers. Hydrolysis of the ester 6, (for example, using a base such a sodium hydroxide in EtOH/H2θ) selectively hydrolyzes the trans, trans ester to give a mixture of 7_ and 8_, which are readily separated. Scheme II illustrates a general procedure for preparing the compounds of the invention when n is 1 , m is 0, Z is -CH2- and W is -CO2H. A substituted benzyl chloride 9_ is reacted with a lithio dithiane 10 in an inert solvent such as THF or dimethoxyethane to give the alkylated adduct 11. The anion of compound H is formed using a base such as n-butyllithium and then reacted with Rι-CH2-X' wherein X' is a leaving group such as a halide or sulfonate to give compound 12. The dithiane protecting group is cleaved (for example, using a mercuric salt in water) to give the keto compound 13.. Reaction of ketone 12. with benzyl amine and formaldehyde gives the keto piperidine compound 14.. Treatment of compound 14 with an activated nitrile such as trimethylsilyl cyanide followed by a dehydrating agent such as phosphorous oxychloride provides the isomeric ene nitriles 15.. Reduction of the double bond (for example, using sodium borohydride) affords the piperidinyl nitrile J_6_. Hydrolysis of the nitrile using hydrochloric acid in the presence of a carboxy protecting reagent (for example, an alkyl alcohol) affords ester 17 (where E is a carboxy protecting group). Debenzylation by catalytic hydrogenation under acidic conditions affords the free piperidine compound 18.. Compound 18 is further elaborated by the procedures described in Scheme I for compound 5_ to give the final product compound 12.. Scheme III illustrates a general procedure for preparing the compounds of the invention when m and n are 0, Z is -C(O)- and W is -CO2H. β-Keto ester 2J2. (wherein E is Ioweralkyl or a carboxy protecting group) is reacted with an α-haloester 21 (where J is lower alkyl or a carboxy protecting group and the halogen is bromine, iodine or chlorine) in the presence of a base such as NaH or potassium tert- butoxide or lithium diisopropylamide in an inert solvent such as THF or dimethoxyethane to give diester 22.. Treating compound 22, with R3-NH2 and heating in acetic acid gives the cyclic compound 23. The double bond is reduced (for example, by catalytic hydrogenation using a palladium on carbon catalyst or sodium cyanoborohydride reduction) to give pyrrolidone 24.- Epimerization with sodium ethoxide in ethanol to give the desired trans.trans configuration, followed by sodium hydroxide hydrolysis of the ester, affords the desired trans.trans carboxylic acid 25.. Scheme IV illustrates a general procedure for preparing the compounds of the invention when n is 0, m is 1 , Z is -CH2- and W is -CO2H. The trans.trans compound 7, prepared in Scheme I, is homologated by the Arndt-Eistert synthesis. The carboxy terminus is activated (for example, by making the acid chloride using thionyl chloride) to give compound 52, where L is a leaving group (in the case of an acid chloride, L is CI). Compound 52. is treated with diazomethane to give the diazo ketone 5_3_. Rearrangement of compound 53. (for example, using water or an alcohol and silver oxide or silver benzoate and triethylamine, or heating or photolysis in the presence of water or an alcohol) affords the acetic acid compound 54 or an ester which may be hydrolyzed. Compounds where m is from 2 to 6 can be obtained by repetition of the above described process. A preferred embodiment is shown in Schemes V and VI. A benzoyl acetate 2_6_ is reacted with a nitro vinyl benzodioxolyl compound 2∑ using 1 ,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as the base in toluene to give compound 28_. Catalytic hydrogenation using Raney nickel leads to reduction of the nitro group to an amine and subsequent cyclization to give the dihydropyrrole 2£. The double bond is reduced with sodium cyanoborohydride to give the pyrrolidine compound 3J) as a mixture of cis-cis, trans.trans and cis,trans isomers. Chromatography separates out the cis-cis isomer, leaving a mixture of the trans.trans and cis, trans isomers (31). Scheme VI illustrates the further elaboration of the trans.trans isomer. The mixture (31 ) of trans.trans and cis, trans pyrrolidines described in Scheme IV is reacted with N-propyl bromoacetamide in acetonitriie in the presence of ethyldiisopropylamine to give the alkylated pyrrolidine compound 32.. still as a mixture of trans.trans and cis, trans isomers. Sodium hydroxide in ethanol-water hydrolyzes the 5 ethyl ester of the trans.trans compound but leaves the ethyl ester of the cis.trans compound untouched, thus allowing separation of the trans, trans carboxylic acid 33. from the cis, trans ester 34.. Scheme VII illustrates the preparation of a specific piperidinyl compound. Benzodioxolyl methyl chloride 35. is reacted with lithio ι o dithiane 36_ to give the alkylated compound 3Z. Treatment of compound 37 with 4-methoxybenzyl chloride in the presence of lithium diisopropylamide gives compound 33. Cleavage of the dithiane protecting group using a mercuric salt in aqueous solution gives ketone 39. Treatment of 32. with benzylamine and formaldehyde gives the keto 15 piperidine 40.. Treatment of compound 40. with trimethylsilyl cyanide followed by phosphorous oxychloride gives the ene nitrile as a mixture of isomers 41. Sodium borohydride reduction of the double bond gives the piperidinyl nitrile 42.. Hydrochloric acid hydrolysis in the presence of ethanol gives ethyl ester 43.. The N-benzyl protecting group is 20 removed by catalytic hydrogenation to give the free piperidine compound 44. Compound 44 is further elaborated by the procedures described in Scheme V for compound 31 resulting in the formation of the N-derivatized carboxylic acid 45.. A preferred embodiment of the process shown in Scheme III is 25 shown in Scheme VIII. 4-Methoxybenzoylacetate 43. (wherein E is Ioweralkyl or a carboxy protecting group) is reacted with an benzodioxolyl α-bromoacetate 47 (wherein E is lower alkyl or a carboxy protecting group) in the presence of NaH in THF to give diester 48. Treating compound 43 with ethoxypropylamine and heating in acetic 30 acid gives the cyclic compound 42. The double bond is reduced by catalytic hydrogenation using a palladium on carbon catalyst to give pyrrolidone 5p_. Epimerization with sodium ethoxide in ethanol to give the desired trans.trans configuration is followed by sodium hydroxide hydrolysis of the ester to afford the desired trans.trans carboxylic acid 35 5J_. Scheme IX illustrates the preparation of compounds where n is 0, Z is -CH2-, and W is other than carboxylic acid. Compound 55., which can be prepared by the procedures described in Scheme IV, is converted (for example, using peptide coupling condition, e.g. N-methylmorpholine, EDCI and HOBt, in the presence of ammonia or other amide forming reactions) to give carboxamide 5. The carboxamide is dehydrated (for example, using phosphorus oxychloride in pyridine) to give nitrile 5Z. Nitrile 5Z under standard tetrazole forming conditions (sodium azide and triethylamine hydrochloride or trimethyisilylazide and tin oxide) is reacted to give tetrazole 53.. Alternatively nitrile 5Z is reacted with hydroxylamine hydrochloride in the presence of a base (for example, potassium carbonate, sodium carbonate, sodium hydroxide, triethylamine, sodium methoxide or NaH) in a solvent such as DMF, DMSO, or dimethylacetamide to give amidoxime 52. The amidoxime 52 is allowed to react with a methyl or ethyl chloroformate in a conventional organic solvent (such as, chloroform, methylene chloride, dioxane, THF, acetonitrile or pyridine) in the presence of a base (for example, triethylamine, pyridine, potassium carbonate and sodium carbonate) to give an O-acyl compound. Heating of the O-acyl amidoxime in an inert solvent (such as benzene, toluene, xylene, dioxane, THF, dichloroethane, or chloroform and the like) results in cyclization to compound 6J1. Alternatively reacting the amidoxime 52 with thionyl chloride in an inert solvent (for example, chloroform, dichloromethane, dixoane and THF and the like) affords the oxathiadiazole 51. Scheme X illustrates the preparation of compounds in which R 3 is an acylmethylene group. A carboxylic acid 32 (where R 4 is as previously defined herein) is treated with oxalyl chloride in a solution of methylene chloride containing a catalytic amount of N,N- dimethylformamide to give the acid chloride. Treatment of the acid chloride with excess ethereal diazomethane affords a diazoketone, and then treatment with anhydrous HCI in dioxane gives the α-chloroketone 63. Pyrrolidine ester 5 where E is lower alkyl or a carboxy protecting group, prepared in Scheme I, is alkylated with the α-chloroketone 5 to provide alkylated pyrrolidine 54. Carboxy deprotection (for example, hydrolysis of an alkyl ester using lithium or sodium hydroxide in ethanol-water) gives the alkylated pyrrolidine acid 55. Scheme XI illustrates the preparation of "reverse amides and sulfonamides". The carboxy protected pyrrolidine 5. prepared in Scheme I, is reacted with a difunctionalized compound X-R 8 -X where R 8 is alkylene and X is a leaving group (for example a halide where Br is preferred) to give N-alkylated compound 55. Treatment of with an amine (R20NH2) affords secondary amine 5Z. This amine (67) can be reacted with an activated acyl compound (for example, R4-C(0)-CI) and then carboxy deprotected (for example, hydrolysis of an ester or hydrogenation of a benzyl moiety) to afford amide SB.. Alternatively amine 5Z can be reacted with an activated sulfonyl compound (for example, Rβ-S(0)2-CI) and then carboxy deprotected (for example, hydrolysis of an ester or hydrogenation of a benzyl moiety) to afford sulfonamide 52. Scheme XII illustrates a method for synthesizing pyrrolidines by an azomethine ylide type [3+2]-cycloaddition to an acrylate. General structures such as compound ZQ are known to add to unsaturated esters such as 71 to provide pyrrolidines such as compound Z2. (O. Tsuge, S. Kanemasa, K. Matsuda, Chem. Lett. 1131-4 (1983), O. Tsuge, S. Kanemasa, T. Yamada, K. Matsuda, J. Org. Chem. 52 2523-30 (1987), and S. Kanemasa, K. Skamoto, O. Tsuge, Bull. Chem. Soc. Jpn. 52 1960-68 (1989)). A specific example is also shown in Scheme XII. Silylimine Z3 is reacted with acrylate J _ in the presence of trimethylsilyl triflate and tetrabutylammonium fluoride to give the desired pyrrolidine 75 as a mixture of isomers. This method can be modified to provide the N- acetamido derivatives directly by reacting 73 and Z4 with the appropriate bromoacetamide (for example, dibutyl bromoacetamide) in the presence of tetrabutylammonium iodide and cesium fluoride to give compound 75. Scheme XIII illustrates a method for producing an enantiomerically pure pyrrolidine 30., which can be further elaborated on the pyrrolidine nitrogen. Intermediate racemic pyrrolidine ester 77 (for example, prepared by the procedure described in Scheme V) is Boc- nitrogen protected (for example, by treatment with B0C2O) and then the ester is hydrolyzed (for example, using sodium or lithium hydroxide in ethanol and water) to give t-butyl carbamoyl pyrrolidine carboxylic acid 7JB_. The carboxylic acid is converted to its (+)-cinchonine salt, which can be recrystaliized (for example from ethyl acetate and hexane or chloroform and hexane) to afford the diastereomerically pure salt. This diastereomerically pure salt can be neutralized (for example, with sodium carbonate or citric acid) to afford enantiomerically pure carboxylic acid Z2.. The pyrrolidine nitrogen can be deprotected (for example, using trifluoroacetic acid) and the ester reformed by the use of ethanolic hydrochloric acid to give salt SO.. Alternatively one can 5 use ethanol HCl to cleave the protecting group and form the ester in one step. The pyrrolidine nitrogen can be further elaborated (for example, by treatment with the dibutyl amide of bromoacetamide in acetonitrile in the presence of diisopropylethylamine) to give optically active compound Bl. The use of (-)-cinchonine will give the opposite ι o enantiomer. Scheme XIV describes another procedure for preparation of pyrrolidines. Pyrrolidines may be synthesized by the use of an azomethine ylide cycloaddition to an acrylate derivative as described by Cottrell, I. F., et.al., J. Chem. Soc, Perkin Trans. 1 , 5: 1091-97 15 (1991). Thus, the azomethine ylide precursor S2. (where R δδ is hydrogen or methyl) is condensed with a substituted acrylate S3, (wherein R2 is as described herein and R5 6 is Ioweralkyl) under acidic conditions to afford the substituted pyrrolidine S4- The N-protecting group can be removed (for example, by hydrogenolysis of an N-benzyl group) to give 0 S5. which can be alkylated under the conditions described above to provide the N-substituted pyrrolidine S£. Standard ester hydrolysis of 86 produces the desired pyrrolidine carboxylic acid SZ. A preferred process is shown in Scheme XV. Nitro vinyl compound (88) is reacted with beta-keto ester 32. in the presence of a base such 25 as sodium ethoxide and the like or a trialkyiamine such as triethylamine or diisopropylethylamine and the like or an amidine such as DBU and the like in an inert solvent such as THF, toluene, DMF, acetonitrile, ethyl acetate, isopropyl acetate or methylene chloride and the like at a temperature of from about 0° C to about 100° C for a 30 period of time from about 15 minutes to overnight to give compound 20. Reduction of the nitro group followed by cyclization was effected for example by catalytic hydrogenation with a hydrogen pressure of from about atmospheric pressure to 300 p.s.i. over from about 1 hour to about 1 day of compound 20 in an inert solvent such as THF, ethyl acetate, 35 toluene, ethanol, isopropanol, DMF or acetonitrile and the like, using a hydrogenation catalyst such as Raney nickel, palladium on carbon, a platinum catalyst, such as platinum oxide, platinum on carbon or platinum on alumina and the like, or a rhodium catalyst, such as rhodium on carbon or rhodium on alumina and the like, and the like affords intermediate nitrone 91 a or a mixture of nitrone 91 a and imine 91 b. The reaction mixture comprising the nitrone or nitrone/imine 5 mixture is treated with an acid such as trifluoroacetic acid or acetic acid or sulfuric acid or phosphoric acid or methanesulfonic acid and the like, and the hydrogenation is continued to give pyrrolidine compound 22 as the c/ ' s,c/s-isomer. Epimerization at C-3 is effected by treatment of compound 22. with a base such as sodium ethoxide, potassium ι o t-butoxide, lithium t-butoxide or potassium t-amyloxide and the like or a trialkylamine such as triethylamine or diisopropylethylamine and the like or an amidine such as DBU and the like in an inert solvent such as ethanol, ethyl acetate, isopropyl acetate, THF, toluene or DMF and the like at a temperature of from about -20° C to about 120° C to give the 15 trans.trans compound 23. Compound 23 itself can optionally be resolved into enantiomers prior to reacting with X-R 3 . The substantially pure (i.e., at least 95% of the desired isomer) optically active (+)-isomer of compound 23 is obtained by treatment of a mixture of the (+)-isomer and the (-)-isomer of 23. with S-(+)-mandelic acid, D- 20 tartaric acid or D-dibenzoyl tartaric acid and the like in a solvent such as acetonitrile, ethyl acetate, isopropyl acetate, ethanol or isopropanol and the like. The (+)-isomer of 23. selectively crystallizes as the salt, leaving the (-)-isomer of 23. in solution. Alternatively, the substantially pure (i.e., 25 at least 95% of the desired isomer) optically active (-)-isomer of compound 23. can be selectively crystallized by reaction of a mixture of the (+)-isomer and the (-)-isomer of 23. with L-tartaric acid, L-dibenzoyl tartaric acid or L-pyroglutamic acid and the like, leaving the desired 30 (+)-isomer of compound 23 in solution. Compound 23. (racemic or optically active) is reacted with X-R3 (where X is a leaving group (for example, a halide or a sulfonate) and R3 is as previously defined) using a base such as diisopropylethylamine, triethylamine, sodium bicarbonate or potassium carbonate and the like 35 in an inert solvent such as acetonitrile, THF, toluene, DMF or ethanol and the like at a temperature of from about 0° C to about 100° C to give the intermediate ester 24- The ester can be isolated or converted in situ to the carboxylic acid (95) using hydrolysis conditions such as a base such as sodium hydroxide or lithium hydroxide or potassium hydroxide and the like in a solvent such as ethanol-water or THF- ethanol and the like. Scheme I [H] Scheme II 10 21 MER Jδ 19 Sche e Halo = CI.Br, or I 22 24 22 Trans-Trans Scheme IV 52 CH 2 N 2 54 53 Scheme V Trans-Trans \ Chromatographic separation Cis-Trans Cis-Cis + Mixture of Trans-Trans and Cis-Trans 31 Scheme VI 22 21 Scheme VII 33 3Z 40 41 Scheme VII cont. Scheme VIII Trans-Trans Scheme IX (CH 2 ) m I C0 2 H CONH 2 55 56 SQ 61 Scheme X 5 £5 ! Scheme XI €5 Scheme XII 7ϋ 71 22 73 74 Scheme XIII 1. (+)-cinchoninβ 2. recrystallize froπ EtOAc/hexane 3. Na 2 C0 3 Bu 2 NC(0)CH 2 Br EtNiPr 2 , CH 3 CN Scheme XIV 82 H 2 ^ R 3 Br Pd(OH) 2 /C H cθ 2 R 56 Bu 4 NlorNal Λ^ CH 3 CN R 2 as SL Scheme XV fiS 88. 22 22 25 4 Compounds which are useful as intermediates for the preparation of compounds of the invention are: (I I I) wherein n is 0 or 1 ; m is 0 to 6; ι o W is (a) -C(0)2-G where G is hydrogen or a carboxy protecting group, (b) -PO3H2. (c) -P(0)(OH)E where E is hydrogen, Ioweralkyl or arylalkyi, (d) -CN, (e) -C(0)NHRi7 where R17 is Ioweralkyl, 15 (f) alkylaminocarbonyl, (g) dialkylaminocarbonyl, (h) tetrazolyl, (i) hydroxy, (j) alkoxy, 0 (k) sulfonamido, (1) -C(0)NHS(0) 2 R i 6 where Rι 6 is Ioweralkyl, haloalkyi, phenyl or dialkylamino, (m) -S(0) 2 NHC(0)Ri6, 5 Ri and R2 are independently selected from hydrogen, Ioweralkyl, alkenyl, alkynyl, alkoxyalkyi, alkoxycarbonylalkyl, hydroxyalkyi, haloalkyi, haloalkoxyalkyi, alkoxyalkoxyalkyl, thioalkoxyalkoxyalkyi, cycloalkyi, cycloalkylalkyl, aminocarbonylalkyl, alkylaminocarbonylalkyl, dialkylaminocarbonyialkyl, aminocarbonylalkenyl, alkylaminocarbonylalkenyl, dialkylaminocarbonylalkenyl, hydroxyalkenyl, aryl, arylalkyi, aryloxyalkyl, arylalkoxy alkyl, (N-alkanoyl-N-alkyl)aminoalkyl, alkylsulfonylamidoalkyl, heterocyclic, (heterocyclic)alkyl and (R aa )(R bb )N-R cc - wherein R aa is aryl or arylalkyi, R bb is hydrogen or alkanoyl and R cc is alkylene, with the proviso that one or both of R 1 and R 2 is other than hydrogen; or a salt thereof; or a compound of the formula: (IV) (V) wherein n is 0 or 1 ; 5 m is 0 to 6; W is (a) -C(0)2-G where G is hydrogen or a carboxy protecting group, (b) -P0 3 H 2 , (c) -P(0)(OH)E where E is hydrogen, Ioweralkyl or arylalkyi, (d) -CN, ι o (e) -C(0)NHR 7 where R 1 7 is Ioweralkyl, (f) alkylaminocarbonyl, (g) dialkylaminocarbonyl, (h) tetrazolyl, (i) hydroxy, 15 (j) alkoxy, (k) sulfonamido, (I) -C(0)NHS(0)2Ri6 where R16 is Ioweralkyl, haloalkyi, phenyl or dialkylamino, (m) -S(0) 2 NHC(0)Ri6, 20 NT \ s=o -^ N (s) H Ri an from hydrogen, Ioweralkyl, alkenyl, alkynyl, alkoxyalkyi, alkoxycarbonylalkyl, hydroxyalkyi, haloalkyi, haloalkoxyalkyi, alkoxyalkoxyalkyl, thioalkoxyalkoxyalkyi, cycloalkyi, cycloalkylalkyl, aminocarbonylalkyl, alkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, aminocarbonylalkenyl, alkylaminocarbonylalkenyl, dialkylaminocarbonylalkenyl, hydroxyalkenyl, aryl, arylalkyi, aryloxyalkyl, arylalkoxyalkyl, (N-alkanoyl-N-alkyl)aminoalkyl, alkylsulfonylamidoalkyl, heterocyclic, (heterocyclic)alkyl and ( R aa)( R bb) N " R cc" wherein R aa is aryl or arylalkyi, R bb is hydrogen or alkanoyl and R cc is alkylene, with the proviso that one or both of R-, and R 2 is other than hydrogen; or a salt thereof. Preferred intermediates include compounds of formula (III), (IV) and (V) wherein m is zero or 1 ; W is -CO2-G wherein G is hydrogen or a carboxy protecting group, and Ri and R2 are as defined above; or the substantially pure (+)- or (-)-isomer thereof. Particularly preferred intermediates are compounds of formula (III), (IV) and (V) wherein n and m are both 0; W is -CO2-G wherein G is hydrogen or a carboxy protecting group; and Ri is (i) Ioweralkyl, (ii) alkenyl, (iii) alkoxyalkyi, (iv) cycloalkyi, (v) phenyl, (vi) pyridyl, (vii) furanyl or (viii) substituted or unsubstituted 4- methoxy phenyl, 4-fluorophenyl, 3-fluorophenyl, 4-ethoxyphenyl, 4-ethylphenyl, 4- methylphenyl, 4-trifluoromethyIphenyl, 4-pentafluoroethylphenyl, 3-fluoro-4- methoxyphenyl, 3-fluoro-4-ethoxyphenyl, 2-fluorophenyl, 4-methoxymethoxyphenyl, 4-hydroxyphenyl, 4-t-butylphenyl, 1 ,3-benzodioxolyl, 1 ,4- benzodioxanyl or dihydrobenzofuranyl wherein the substituent is selected from Ioweralkyl, haloalkyi, alkoxy, alkoxyalkoxy and carboxyalkoxy (ix) aryalkyl, (x) aryloxyalkyl, (xi) heterocyclic (alkyl), (xii) (N-alkanoyl-N-alkyl)aminoalkyl, and (xiii) alkylsulfonylamidoalkyl, and R 2 is substituted or unsubstituted 1 ,3-benzodioxolyl, 7-methoxy- 1 ,3-benzodioxolyl, 1 ,4-benzodioxanyl, 8-methoxy-1 ,4-benzodioxanyl, dihydrobenzofuranyl, benzofurnayl, 4-methoxy phenyl, dimethoxyphenyl, fluorophenyl or difluorophenyl wherein the substituent is selected from Ioweralkyl, alkoxy and halogen; or the substantially pure (+)- or (-)-isomer thereof. Other compounds which are useful as intermediates for the preparation of compounds of the invention are: (VI) wherein n is 0 or 1 ; m is 0 to 6; R 5b is alkylene; Q is a leaving group; W is (a) -C(0)2-G where G is hydrogen or a carboxy protecting group, (b) -PO3H2, (c) -P(0)(OH)E where E is hydrogen, Ioweralkyl or arylalkyi, (d) -CN, (e) -C(0)NHRi7 where R17 is Ioweralkyl, (f) alkylaminocarbonyl, (g) dialkylaminocarbonyl, (h) tetrazolyl, (i) hydroxy, (j) alkoxy, (k) sulfonamido, (I) -C(0)NHS(0)2Ri6 where R16 is Ioweralkyl, haloalkyi, phenyl or dialkylamino, (m) -S(0) 2 NHC(0)Ri6, (q) N-°N s=o ^ » (s) 5 Ri and R 2 are independently selected from hydrogen, Ioweralkyl, alkenyl, alkynyl, alkoxyalkyi, alkoxycarbonylalkyl, hydroxyalkyi, haloalkyi, haloalkoxyalkyi, alkoxyalkoxyalkyl, thioalkoxyalkoxyalkyi, cycloalkyi, cycloalkylalkyl, aminocarbonylalkyl, alkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, ι o aminocarbonylalkenyl, alkylaminocarbonylalkenyl, dialkylaminocarbonylalkenyl, hydroxyalkenyl, aryl, arylalkyi, aryloxyalkyl, arylalkoxyalkyl, (N-alkanoyl-N-alkyl)aminoalkyl, alkylsulfonylamidoalkyl, heterocyclic, (heterocyclic)alkyl and (R aa )(R bb )N-R cc - wherein R aa is aryl or arylalkyi, R bb is hydrogen or i s alkanoyl and R cc is alkylene, with the proviso that one or both of R 1 and R 2 is other than hydrogen; or a salt thereof; or a compound of the formula: (V I I ) wherein n is 0 or 1 ; m is 0 to 6; R 5b is alkylene; Q is a leaving group; W is (a) -C(0)2-G where G is hydrogen or a carboxy protecting group, (b) -PO3H2, (c) -P(0)(OH)E where E is hydrogen, Ioweralkyl or arylalkyi, (d) -CN, (e) -C(0)NHRi7 where R17 is Ioweralkyl, (f) alkylaminocarbonyl, (g) dialkylaminocarbonyl, (h) tetrazolyl, (i) hydroxy, (j) alkoxy, (k) suifonamido, (I) -C(0)NHS(0) 2 Ri6 where R16 is Ioweralkyl, haloalkyi, phenyl or dialkylamino, (m) -S(0) 2 NHC(0)Ri6, NT \ s=o -^ N H (S) Ri and R2 are independently selected from hydrogen, Ioweralkyl, alkenyl, alkynyl, alkoxyalkyi, alkoxycarbonylalkyl, hydroxyalkyi, haloalkyi, haloalkoxyalkyi, alkoxyalkoxyalkyl, thioalkoxyalkoxyalkyi, cycloalkyi, cycloalkylalkyl, aminocarbonylalkyl, alkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, aminocarbonylalkenyl, alkylaminocarbonylalkenyl, dialkylaminocarbonylalkenyl, hydroxyalkenyl, aryl, arylalkyi, aryloxyalkyl, arylalkoxyalkyl, (N-alkanoyl-N-alkyl)aminoalkyl, alkylsulfonylamidoalkyl, heterocyclic, (heterocyclic)alkyl and (R aa )(R bb )N-R cc - wherein R aa is aryl or arylalkyi, R bb is hydrogen or alkanoyl and R cc is alkylene, with the proviso that one or both of R 1 and R 2 is other than hydrogen; or a salt thereof. Preferred intermediates include compounds of formula (VI), (VII) and (VIII) wherein m is zero or 1 ; R 5b is alkylene; Q is a leaving group; W is -CO2-G wherein G is hydrogen or a carboxy protecting group, and Ri and R 2 are as defined above; or the substantially pure (+)- or (-)-isomer thereof. Particularly preferred intermediates are compounds of formula (VI), (VII) and (VIII) wherein n and m are both 0; R 5b is alkylene; Q is a leaving group; W is -CO2-G wherein G is hydrogen or a carboxy protecting group; and Ri is (i) Ioweralkyl, (ii) alkenyl, (iii) alkoxyalkyi, (iv) cycloalkyi, (v) phenyl, (vi) pyridyl, (vii) furanyl or (viii) substituted or unsubstituted 4-methoxyphenyl, 4-fluorophenyl, 3-fluorophenyl, 4-ethoxyphenyI, 4-ethylphenyl, 4- 5 methylphenyl, 4-trifluoromethylphenyl, 4-pentafluoroethylphenyl, 3-fluoro-4- methoxyphenyl, 3-fluoro-4-ethoxyphenyl, 2-fluorophenyl, 4-methoxymethoxyphenyl, 4-hydroxyphenyl, 4-t-butylphenyl, 1 ,3-benzodioxolyl, 1 ,4- ι o benzodioxanyl or dihydrobenzofuranyl wherein the substituent is selected from Ioweralkyl, haloalkyi, alkoxy, alkoxyalkoxy and carboxyalkoxy, (ix) aryalkyi, (x) aryloxyalkyl, (xi) heterocyclic (alkyl), (xii) (N-alkanoyl-N-alkyl)aminoalkyl, and (xiii) alkylsulfonylamidoalkyl, and R 2 is substituted or unsubstituted 1 ,3-benzodioxolyl, 7-methoxy- 15 1 ,3-benzodioxolyl, 1 ,4-benzodioxanyl, 8-methoxy-1 ,4-benzodioxanyl, dihydrobenzofuranyl, benzofurnayl, 4-methoxyphenyl, dimethoxyphenyl, fluorophenyl or difluorophenyl wherein the substituent is selected from Ioweralkyl, alkoxy and halogen; or 20 the substantially pure (+)- or (-)-isomer thereof. Other compounds which are useful as intermediates for the preparation of compounds of the invention are: - NHRzo a (IX) wherein n is 0 or 1 ; m is 0 to 6; 30 R 5b is alkylene; R 2 0 a is hydrogen, ioweralkyl, alkenyl, haloalkyi, alkoxyalkyi, haloalkoxyalkyi, cycloalkyi, cycloalkylalkyl, aryl or arylalkyi; W is (a) -C(0)2-G where G is hydrogen or a carboxy protecting group, (b) -PO3H2, (c) -P(0)(OH)E where E is hydrogen, Ioweralkyl or arylalkyi, (d) -CN, (e) -C(0)NHRi7 where R17 is Ioweralkyl, (f) alkylaminocarbonyl, (g) dialkylaminocarbonyl, (h) tetrazolyl, (i) hydroxy, (j) alkoxy, (k) sulfonamido, (I) -C(0)NHS(0)2Rιβ where R16 is Ioweralkyl, haloalkyi, phenyl or dialkylamino, (m) -S(0) 2 NHC(0)Ri6, (s) Ri and R2 are independently selected from hydrogen, Ioweralkyl, alkenyl, alkynyl, alkoxyalkyi, alkoxycarbonylalkyl, hydroxyalkyi, haloalkyi, haloalkoxyalkyi, alkoxyalkoxyalkyl, thioalkoxyalkoxyalkyi, cycloalkyi, cycloalkylalkyl, aminocarbonyialkyl, alkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, aminocarbonylalkenyl, alkylaminocarbonylalkenyl, dialkylaminocarbonylalkenyl, hydroxyalkenyl, aryl, arylalkyi, aryloxyalkyl, arylalkoxyalkyl, (N-alkanoyl-N-alkyl)aminoalkyl, alkylsulfonylamidoalkyl, heterocyclic, (heterocyclic)alkyl and ( R aa)( R bb) N " R cc" wherein R aa is aryl or arylalkyi, R bb is hydrogen or alkanoyl and R cc is alkylene, with the proviso that one or both of R 1 and R 2 is other than hydrogen; or a salt thereof; or a compound of the formula: - NHR 20a - NHRzoa (X) (XI) wherein n is 0 or 1; m is 0 to 6; R 5b is alkylene; R 20a is hydrogen, Ioweralkyl, alkenyl, haloalkyi, alkoxyalkyi, haloalkoxyalkyi, cycloalkyi, cycloalkylalkyl, aryl or arylalkyi; W is (a) -C(0)2-G where G is hydrogen or a carboxy protecting group, (b) -PO3H2, (c) -P(0)(OH)E where E is hydrogen, Ioweralkyl or arylalkyi, (d) -CN, (e) -C(0)NHR-|7 where R 1 7 is Ioweralkyl, (f) alkylaminocarbonyl, (g) dialkylaminocarbonyl, (h) tetrazolyl, (i) hydroxy, (j) alkoxy, (k) sulfonamido, (I) -C(0)NHS(0)2Rιβ where Riβ is Ioweralkyl, haloalkyi, phenyl or dialkylamino, (m) -S(0) 2 NHC(0)Ri6, r - C s=o (t) , or Ri and R 2 are independently selected from hydrogen, Ioweralkyl, alkenyl, alkynyl, alkoxyalkyi, alkoxycarbonylalkyl, hydroxyalkyi, haloalkyi, haloalkoxyalkyi, alkoxyalkoxyalkyl, thioalkoxyalkoxyalkyi, 5 cycloalkyi, cycloalkylalkyl, aminocarbonylalkyl, alkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, aminocarbonylalkenyl, alkylaminocarbonylalkenyl, dialkylaminocarbonylalkenyl, hydroxyalkenyl, aryl, arylalkyi, aryloxyalkyl, arylalkoxyalkyl, (N-alkanoyl-N-alkyl)aminoalkyl, ι o alkylsulfonylamidoalkyl, heterocyclic, (heterocyclic)alkyl and ( R aa)( R b b ) N " R cc* wherein R aa is aryl or arylalkyi, R bb is hydrogen or alkanoyl and R cc is alkylene, with the proviso that one or both of R 1 and R 2 is other than hydrogen; or a salt thereof. 15 Preferred intermediates include compounds of formula (IX), (X) and (XI) wherein m is zero or 1 ; R 5b is alkylene; R 20a ' s hydrogen, Ioweralkyl, alkenyl, haloalkyi, alkoxyalkyi, 20 haloalkoxyalkyi, cycloalkyi, cycloalkylalkyl, aryl or arylalkyi; W is -CO2-G wherein G is hydrogen or a carboxy protecting group, and Ri and R2 are as defined above; or the substantially pure (+)- or (-)-isomer thereof. Particularly preferred intermediates are compounds of formula 25 (IX), (X) and (XI) wherein n and m are both 0; R 5b is alkylene; R 20a is hydrogen, Ioweralkyl, alkenyl, haloalkyi, alkoxyalkyi, haloalkoxyalkyi, cycloalkyi, cycloalkylalkyl, aryl or arylalkyi; 30 W is -CO 2 -G wherein G is hydrogen or a carboxy protecting group; and Ri is (i) Ioweralkyl, (ii) alkenyl, (iii) alkoxyalkyi, (iv) cycloalkyi, (v) phenyl, (vi) pyridyl, (vii) furanyl or (viii) substituted or unsubstituted 4-methoxyphenyl, 4-fluorophenyl, 3-fluorophenyl, 4- ethoxyphenyl, 4-ethylphenyl, 4-methylphenyl, 4-trifluoromethylphenyl, 35 4-pentafluoroethylphenyl, 3-fluoro-4-methoxyphenyl, 3-fluoro-4- ethoxyphenyl, 2-fluorophenyl, 4-methoxymethoxyphenyl, 4- hydroxyphenyl, 4-t-butyIphenyl, 1 ,3-benzodioxolyl, 1 ,4-benzodioxanyl or dihydrobenzofuranyl wherein the substituent is selected from Ioweralkyl, haloalkyi, alkoxy, alkoxyalkoxy and carboxyalkoxy, (ix) aryalkyi, (x) aryloxyalkyl, (xi) heterocyclic (alkyl), (xii) (N-alkanoyl-N- alkyl)aminoalkyl, and (xiii) alkylsulfonylamidoalkyl, and R 2 is substituted or unsubstituted 1 ,3-benzodioxolyl, 7-methoxy-1 ,3- benzodioxolyl, 1 ,4-benzodioxanyl, 8-methoxy-1 ,4-benzodioxanyl, dihydrobenzofuranyl, benzofurnayl, 4-methoxyphenyl, dimethoxyphenyl, fluorophenyl or difluorophenyl wherein the substituent is selected from Ioweralkyl, alkoxy and halogen; or the substantially pure (+)- or (-)-isomer thereof. The foregoing may be better understood by reference to the following examples which are provided for illustration and not intended to limit the scope of the inventive concept. The following abbreviations are used: Boc for tert-buty loxycarbonyl, Cbz for benzyloxycarbonyl, DBU for 1 ,8-diazabicyclo[5.4.0]undec-7-ene, EDCI for 1-(3- dimethylaminopropyl-3-ethylcarbodiimide hydrochloride, EtOAc for ethyl acetate, EtOH for ethanol, HOBt for 1-hydroxybenzotriazole, Et 3 N for triethylamine, TFA for trifluoroacetic acid and THF for tetrahydrofuran. Example 1 trans.trans- 2-f4-Methoxyphenvh-4-π .3-benzodioxol-5-vπ-1- (propylam.nocarbonylmethylVpyrrolidine-3-carboxylic acid Example 1A Ethyl 2-f4-methoxybenzovπ-4-nitromethyl-3- 1.3-benzodioxole-5-vhbutyrate To ethyl (4-methoxybenzoyl)acetate (23.0 g, 0.104 mol), prepared by the method of Krapcho et al., Org. Syn. 4∑, 20 (1967), and 5-(2- nitrovinyl)-1 ,3-benzodioxole (17.0 g, 0.088 mol) dissolved in 180 mL of toluene and heated to 80 °C was added 1 ,8-diazabicyclo[5,4,0] undec-7- ene (DBU, 0.65 g) with stirring. The mixture was heated until all the nitro starting material dissolved. The solution was stirred without heating for 30 minutes (min) and then an additional 0.65 g of DBU was added. After stirring an additional 45 minutes, thin layer chromatography (5% ethyl acetate in methylene chloride) indicated the absence of nitro starting material. Toluene (200 mL) was added, and the organic phase was washed with dilute hydrochloric acid and NaCI solution. The organic phase was dried over sodium sulfate and then concentrated under reduced pressure. The residue obtained was chromatographed on silica gel eluting with 3:1 hexane-ethyl acetate to give 21.22 g of the desired product as a mixture of isomers and 9.98 g. of recovered ethyl (4-methoxybenzoyl)acetate. Example 1B Ethvl 2-f4-methoxvphenvl -f1.3-benzodioxol-5-yn-4.5-dihvdro-3H-Pyrrole-3- carboxylate The compound resulting from Example 1A (21 g) in 500 mL of ethanol was hydrogenated under 4 atmospheres of hydrogen pressure using a Raney nickel 2800 catalyst (51 g). (The Raney nickel was washed with ethanol three times before use.) The catalyst was removed by filtration, and the solution was concentrated under reduced pressure. The residue obtained was chromatographed on silica gel eluting with 8.5% ethyl acetate in methylene chloride to give 12.34 g of the desired product. Example 1C Ethyl 2-(4-methoxyphenyl-4-f1.3-benzodioxol-5-vn-Pvrrolidine-3-carboxylate) as a mixture of cis-cis: trans.trans: and c/s. raπs-isomers The compound resulting from Example 1B (11.89 g, 0.324 mol) was dissolved in 27 mL of tetrahydrofuran and 54 mL of ethanol. Sodium cyanoborohydride (2.35 g, 0.374 mol) and 5 mg bromocresol green were added. To this blue solution was added dropwise a solution of 1 :2 concentrated HCl in ethanol at such a rate that the color was kept at light yellow-green. After the yellow color persisted without additional HCl, the solution was stirred an additional 20 minutes. The solution was concentrated in vacuo and then partitioned between chloroform and an aqueous potassium bicarbonate solution. The organic phase was separated, dried over sodium sulfate, and concentrated under reduced pressure. The residue was chromatographed on silica gel eluting with 85:15 ethyl acetate-hexane to give 5.96 g. of a mixture of 64% trans, frans-compound and 34% c/s,frans-compound. Further elution with pure ethyl acetate gave 0.505 g of an unknown solid followed by 3.044 g of pure cis, cis- com pound. Example 1 5 fraπs.fraπs-2-f4-Methoxvphenvn-4-(1.3-benzodioxol-5-vn-1 - ropvlaminocarbonvlmethvlVpvrrolidine-3-carboxvlic acid The mixture of 64% trans, trans- and 34% cis, frans-pyrrolidines (the mixture resulting from Example 1C) (5.72 g, 15.50 mmol), ethyldiisopropylamine (4.20 g, 32.56 mmol), and N-propyl ι o bromoacetamide (3.42 g, 19.0 mmol), prepared by the method of Weaver, W.E. and Whaley, W.M., J. Amer. Chem. Soc, £9_: 515 (1947), in 30 mL of acetonitrile was heated at 50 °C for 1 hour. The solution was concentrated in vacuo. The residue was dissolved in toluene, shaken with potassium bicarbonate solution, dried over sodium sulfate and 5 concentrated in vacuo to give 7.16 g of product as a mixture of trans. trans- and cis, trans- ethyl esters. This mixture was dissolved in a solution of 50 mL of ethanol and 15 mL of water containing 5.00 g of sodium hydroxide and stirred for 3 hours at room temperature. The solution was concentrated in vacuo and 0 60 mL of water added. The mixture was extracted with ether to remove the unreacted cis, trans- ethyl ester. The aqueous phase was treated with hydrochloric acid until slightly cloudy. It was then further neutralized with acetic acid to give the crude acid product. The crude product was filtered and purified by dissolving it in tetrahydrofuran, 25 drying over sodium sulfate, concentrating in vacuo, and crystallizing from ether to give 3.230 g of the title compound, m.p. 151-153 °C. 1 H NMR (CD3OD, 300 MHz) δ 0.87 (t, J = 7 Hz, 3H), 1.49 (sextet, J = 7 Hz, 2H), 2.84 ( d, J = 16 Hz, 1 H), 2.95-3.20 (m, 4H), 3.20 (d, J = 16 Hz, 1 H), 3.34-3.42 (m, 1 H), 3.58-3.66 (m, 1 H), 3.78 (s, 3H), 3.88 (d, J = 10 Hz, 30 1 H), 5.92 (s, 2H), 6.75 (d, J = 8 Hz, 1 H), 6.86 (dd, J= 8 Hz, J = 1 Hz, 1 H), 6.90 (d, J = 9 Hz, 2H), 7.02 (d, J = 1 Hz, 1H), 7.40 (d, J = 9 Hz, 2H). Exam le 2 /rans. ran5-2-(4-Methoxvphenvh-4-n .3-benzodiQxol-5-vn.1- 35 (aminocarbonvlmethvn-Pvrrolidine-3-carboxvlic acid Using the method described in Example 1 D, 300 mg of the mixture of 64% trans, trans- and 34% cis, frans-pyrrolidines (the mixture resulting from Example 1C), 220 mg of diisopropylethylamine and 184 mg iodoacetamide were reacted at 45 °C in 1 mL acetonitrile to give 291 mg of a mixture of trans. trans- and cis.trans- N-alkylated esters. A portion (270 mg.) was hydrolyzed with 200 mg NaOH in 1 mL of water and 3 mL of ethanol; a chloroform extraction was used to remove the unreacted cis.trans- ethyl ester. The isolation and purification procedures described in Example 1 D were used to give 134 mg of the title compound, m.p. 246-248 °C. 1 H NMR (DMSO-d 6 , 300 MHz) δ 2.61 (d, J = 16 Hz, 1 H), 2.71 (t, J = 9 Hz, 1 H), 2.90 (t, J = 9 Hz, 1 H), 2.98 (d, J = 16 Hz, 1 H),3.25-3.35 (m, 1 H), 3.45-3.55 (m, 1 H), 3.71 (s, 3H), 3.75 (d, J = 10 Hz, 1 H), 6.00 (s, 2H), 6.81 (s, 2H), 6.90 (d, J = 8 Hz, 2H), 7.10 (s, 1 H), 7.17 (s, 1 H), 7.34 (s, 1 H), 7.38 (d, J = 8 Hz, 2H). Example 3 frans.frans-2- ( 4-Methoxv p henyn-4-f1.3-benzodioxol-5-vIV1-f4-fluorobenzyl)- pyrrolidine-3-carboxylic acid Using the method described in Example 1 D, 300 mg of the mixture of 64% trans.trans- and 34% cis.trans- pyrrolidines (the mixture resulting from Example 1C), 220 mg of diisopropylethylamine and 185 mg of 4-fluorobenzyl bromide were reacted at room temperature for 3 hours in 1 mL of acetonitrile to give 387 mg of a mixture of trans.trans- and c/s.frans-N-alkylated esters. A portion (360 mg) was hydrolyzed with 250 mg NaOH in 1 mL of water and 4 mL of ethanol to give 160 mg of the title compound as an amorphous powder. n H NMR (CDCI 3 , 300 MHz) δ 2.74 (t, J = 9 Hz, 1H), 2.95 (t, J = 7 Hz, 1 H), 2.98 (d, J = 14, 1 H), 3.07 (dd, J = 9 Hz, 1 Hz, 1 H), 3.42-3.53 (m, 1 H), 3.70 (d, J = 9 Hz, 1 H), 3.78 (d, J = 14, 1 H), 3.81 (s, 3H), 5.92 (s, 2H), 6.70 (d, J = 8 Hz, 1 H), 6.77 (dd, J = 8 Hz, 1 Hz, 1 H), 6.91 (d, J = 9 Hz, 2H), 6.94 -7.00 (m, 3H), 7.20 - 7.25 (M, 1 H), 7.44 (d, J = 9 Hz, 2H). Example 4 frans. frans-2-(4- ethoxyphenvn-4-f1.3-benzodioxol-5-vn-1-(2-ethoxyethvn- pyrrolidine-3-carboxylic acid Using the method described in Example 1 D, 300 mg. of the mixture of 64% trans.trans- and 34% cis, frans-pyrrolidines (the mixture resulting from Example 1 C), 220 mg of diisopropylethylamine and 152 mg of 2-bromoethyl ethyl ether were refluxed in 1.5 mL acetonitrile for 3 hours (bath temperature at 95 °C) to give 346 mg of a mixture of trans.trans- and c/s,frans-esters. Hydrolysis with 250 mg NaOH in 1 mL of water and 3 mL of ethanol afforded 140 mg of the title compound, m.p. 88 - 90 °C. H NMR (CDCI 3 . 300 MHz) δ 1.25 (t, J = 7 Hz, 3H), 2.21- 2.32 (m, 1 H), 2.70-2.80 (m, 1 H), 2.85-2,94 (m, 2H), 3.38-3.55 (m, 6H), 3.67 (d, J = 10 Hz, 1H), 3.79 (s, 3H), 5.94 (s, 2H), 6.72 (d, J = 8 Hz, 1H), 6.84 (m, 1H), 6.84 (d, J = 9 Hz, 2H), 7.08 (d, J = 1 Hz, 1H), 7.33 (d, J = 9 Hz, 2H). Example 5 frans.frans-2-(4- ethoxvphenvn-4-f1.3-benzodioxol-5-vn-1-f2-oropoxyethyn- pyrrQlidine-3-carbρxylic acid Using the method described in Example 1D, 520 mg of the mixture resulting from Example 1C, 364 mg of diisopropylethylamine, 50 mg potassium iodide and 350 mg 2-chloroethyl propyl ether were reacted at 125 °C in 0.5 mL acetonitrile for 4 hours to give 517 mg of a mixture of trans.trans- and c/s,frans-esters. A portion (500 mg) was hydrolyzed with 315 mg NaOH in 1 mL of water and 4 mL of ethanol to give 225 mg of the title compound as an amorphous powder. 1 H NMR (CDCI 3 , 300 MHz) δ 0.87 (t, J = 7 Hz, 3H), 1.53 (sextet, J = 7 Hz, 2H), 2.28-2.41 (m, 1H), 2.71-2.83 (m, 1 H), 2.92-3.08 (m, 2H), 3.30 (t, J = 7 Hz, 2H), 3.40-3.60 (m, 4H), 3.72-3.83 (m, 1 H), 3.76 (s, 3H), 5.92 (s, 2H), 6.71 (d, J = 8 Hz, 2H), 6.74 (dd, J = 8 Hz, 1 Hz), 6.71 (d, J = 9 Hz, 2H), 7.07 (d, J = 9 Hz, 2H), 7.73 (d, J = 9 Hz, 2H). Example 6 trans. frans-2-(4-Methoxvphenvn-4-( 1.3-benzodioxol-5-vn-1 -f2-f2- methoxvethoxv)ethvn-Pvrrolidine-3-carboxylic acid Example 6A Ethyl frans. frans-2- 4-methoxyphenvn-4-M .3-benzodioxol-5-vh pyrrolidine-3- carboxvlate To the pure cis, c/s-compound resulting from Example 1C (3.02 g) dissolved in 10 mL of ethanol was added 20 drops of a solution of 21% sodium ethoxide in ethanol. The reaction mixture was refluxed overnight, at which time thin layer chromatography in ethyl acetate indicated the absence of starting material. The NaOEt was neutralized with HCl in ethanol, and the solution was concentrated in vacuo. The residue was taken up in toluene and extracted with potassium bicarbonate in water. The toluene was dried over sodium sulfate and concentrated under reduced pressure to give 2.775 of the title 5 compound which was pure by TLC (ethyl acetate). Example 6B trans. frans-2- 4-Methoxyphenvn-4-M .3-benzodioxol-5-vπ-1 -\2-(2- methoxvethoxv thvll-Pvrrolidine-3-carboxylic acid ι o Using the method described in Example 1D, 250 mg of the compound resulting from Example 6A, 150 mg of 2-(2- methoxyethoxy)ethyl bromide and 175 mg diisopropyl-ethylamine in 1 mL acetonitrile were heated at 100 °C for 3 hours to give 229 mg of the frans, fraπs-ester. A portion (200 mg) was hydrolyzed with 125 mg 15 NaOH in 1 mL of water and 2 mL of ethanol to give 151 mg of the title compound as an amorphous powder. 1 H NMR (CD3OD, 300 MHz) δ 2.9-3.9 (m, 13H), 3.81 (s, 3H), 4.49 (d, J = 10 Hz, 1H), 5.94 (s, 2H), 6.79 (d, J = 8 Hz, 1H), 6.89 (dd, J = 8 Hz, 1 Hz, 1H), 7.00 (d, J = 9 Hz, 2H), 7.05 (d, J = 1 Hz, 1 H), 7.49 (d, J = 9 Hz, 2H). 20 Exam le 7 frans. frans-2-(4-MethoxvphenvlV4-f1.3-benzodioxol-5-vn-1-r2- 2-pvridvnethvn- pyrrolidine-3-carboxylic acid The compound resulting from Example 6A (250 mg), 2-vinyl 25 pyridine (355 mg) and one drop of acetic acid were dissolved in 2- methoxy ethanol, and stirred at 100 °C for 2.5 hours. Toluene was added, and the solution was washed with potassium bicarbonate solution. The solution was dried over potassium bicarbonate and concentrated in vacuo. Toluene was added and the solution re- 30 concentrated. This was done until the odor of 2-vinylpyridine was gone. The residue was taken up in hot heptane, filtered to remove a small amount of insoluble impurity, and concentrated in vacuo to give 225 mg of intermediate ester. The ester was hydrolyzed by the method described in Example 1D to give 202 mg of the title compound as the 35 dihydrate. m.p. 77-80 °C. 1 H NMR (CD3OD, 300 MHz) δ 2.8 - 3.3 (m, 6H), 3.55-3.70 (m, 2H), 3.76 (s, 3H), 3.99 (d, J = 10 Hz, 1H), 5.92 (d, J = 1 Hz, 2H), 6.72 (d, J = 8 Hz, 1H), 6.80 (dd, J = 8 Hz, 1 Hz), 6.85 (d, J = 9 Hz, 2H), 6.92 (d, J = 1 Hz, 1 H), 7.20 (d, J = 9 Hz, 2H), 7.20-7.32 (m, 2H), 7.70-7.80 (m, 2H), 8.40 (d, J = 4 Hz, 1 H). Example 8 5 frans.frans-2- 4-Methoxyphenvn-4-M.3-benzodioxol-5-vn-1-i / moroholin-4- vlcarbonvn-Pvrrolidine-3-carboxvlic acid To the compound resulting from Example 6A (300 mg) and 164 mg triethylamine dissolved in 2 mL of methylene chloride and cooled in an ice bath was added 146 mg 1-morpholinocarbonyl chloride. The mixture ι o was stirred 3 hours at room temperature. Toluene was added and the solution was washed with potassium bicarbonate solution, dried over sodium sulfate and concentrated in vacuo to give the intermediate ester. The ester was hydrolyzed by the method described in Example 1D to give 288 mg of the title compound, m.p. 244-246 °C. 1 H NMR (DMSO- 15 d 6 , 300 MHz) δ 2.96 (dd, J = 12,Hz, 13 Hz, 1H), 3.03-3.13 (m, 2H), 3.20- 3.30 (m, 2H), 3.40-3.60 (m, 5H), 3.74 (s, 3H), 3.70-3.85 (m, 3H), 5.10 (d, J = 10 Hz, 1 H), 5.99 (d, J = 1 Hz, 2H), 6.80-6.90 (m, 2H), 6.87 (d, J = 9 Hz, 2H), 7.07 (s, 1H), 7.25 (d, J = 9 Hz, 2H). 20 Example 9 frans.frans-2- 4-Methoxvphenvh-4-f1.3-benzodioxole-5-vn-1-(butylaminocarbonvn- pyrrQlidiηe-3-ς3 Qxyliς acjd To the compound resulting from Example 6A (300 mg) dissolved in 2 mL tetrahydrofuran and cooled in an ice bath was added 88 mg of 25 butyl isocyanate. After 40 minutes at room temperature, toluene was added, and the solution was concentrated in vacuo to give the intermediate ester. The ester was hydrolyzed by the method described in Example 1 D to give 232 mg of the title compound, m.p. 220-221 °C. 1 H NMR (DMSO-de, 300 MHz) δ 0.78 (t, J = 7 Hz, 3H), 1.10 (sextet, J = 7 30 Hz, 2H), 1.22 (quintet, J = 7 Hz, 2H), 2.78-3.05 (m, 3H), 3.40-3.56 (m, 2H), 3.74 (s, 3H), 3.95-4.05 (m, 1H), 4.93 (d, J = 9 Hz, 1 H), 5.80 (t, broad, J = 7 Hz, 1 H), 5.99 (s, 2H), 6.78-6.86 (m, 2H), 6.88 (d, J = 9 Hz, 2H), 7.00 (d, J = 1 Hz, 1H), 7.12 (d, J = 9 Hz, 2H). Example 10 frans. frans-2-f 4-Methoxvphenvn-4-n .3-benzodioxol-5-vn-1 -t4- methoxyphenylaminocarbonvπ-3-Pyrrolidine-3-carboxylic acid The compound resulting from Example 6A (300 mg) was treated with 133 mg of 4-methoxyphenyl isocyanate by the procedure described in Example 9. The resulting ester was hydrolyzed with NaOH using the method described in Example 1 D to give 279 mg of the title compound, m.p. 185-187 °C. 1 H NMR (CDCI3, 300 MHz) δ 3.23 (dd, J = 12 Hz, 13 Hz, 1H), 3.55-3.68 (m, 2H), 3.72 (s, 3H), 3.83 (s, 3H), 4.50-4.65 (m, 1H), 5.06 (d, J = 10 Hz, 1H), 5.90 (s, 1H), 5.95 (s, 1H), 6.72 (d, J = 9 Hz, 2H), 6.7-6.8 (m, 3H), 6.92 (d, J = 9 Hz, 2H), 6.97 (d, J = 9 Hz, 2H), 7.37 (d, J = 9 Hz, 2H). Example 11 frans. frans^-^-Methoxvphenvl -n.S-beπzodioxol-S-yn-l-acetvlPvrrolidine-a- carboxylic acid The compound resulting from Example 6A (250 mg) in 0.5 mL of toluene was treated with 200 mg of acetic anhydride. After stirring 2 hours at room temperature, water was added and the acetic acid neutralized with potassium bicarbonate. The mixture was extracted with toluene to give 273 mg of the intermediate ester. A portion of the ester (200 mg) was hydrolyzed using the method of Example 1D to give 211 mg of the title compound, m.p. 248-250 °C. Rotational isomers are seen in the NMR. 1 H NMR (DMSO-d 6 , 300 MHz) δ 1.55 and 2.00 (s, 3H), 2.94 and 3.03 (dd, J = 12 Hz, 13 Hz, 1H), 3.3-3.6 (m, 2H), 3.72 and 3.76 (s, 3H), 4.12 and 4.28 (dd, J = 12 Hz, 7 Hz, 1H), 4.95 and 5.04 (d, J = 10Hz, 1H), 6.00 (s, 2H), 6.75-6.87 (m, 3H), 6.95 and 7.04 (d, J = 9 Hz, 2H), 7.18 and 7.32 (d, J = 9 Hz, 2H). Example 12 frans.frans-2-(4-Methoxyphenvn-4-f1.3-benzodioxol-5-vlV1-(2-furoyn-pyrrolidine-3- carboxylic acid To the compound resulting from Example 6A (300 mg) and 164 mg triethylamine dissolved in 2 mL methylene chloride and cooled in an ice bath was added 138 mg of 2-furoyl chloride. The mixture was stirred 30 minutes at room temperature and then worked up by the procedures described in Example 8 to give the intermediare ester. The ester was hydrolyzed by the procedure described in Example 1 D to give 269 mg of the title compound as an amorphous powder. 1 H NMR (DMSO-dβ, 300 MHz) δ 3.06 (dd, J = 12 Hz, 13 Hz, 1H), 3.3-3.6 (m, 2H), 4.25 (m, 1H), 5.19 ( d, J = 10 Hz, 1H), 6.67.4 (m, 8H), 7.8-7.9 (m, 1 H). 5 Example 13 frans. frans-2- 4-Methoxvphenvn-4-M.3-benzodioxol-5-vn-1- fphenvlaminocarbonvn-pvrrolidine-3-carboxylic acid Starting with the compound resulting from Example 6A, phenyl ι o isocyanate and the procedures described in Example 9, the title compound was prepared, m.p. 209-211 °C. 1 H NMR (DMSO-dβ, 300 MHz) δ 3.03 (dd, 1 H), 3.55 (m, 1 H), 3.70 (m, 1H), 3.72 (s, 3H), 4.15 (m, 1H), 5.13 (d, 1H), 6.00 (s, 2H), 6.88 (m, 5H), 7.07-7.20 (m, 3H), 7.30 (d, 2H), 7.38 (d, 2H), 8.20 (bs, 1 H). 1 5 Example trans. frans-2-(4-MethoxvphenvIV4-(1.3-benzodioxol-5-yπ-1 - ,allvlaminocarbonvlmethvh-Pvrrolidine-3-carboxvlic acid Using the procedures described in Example 1 the title compound 20 was prepared, m.p. 138-140 °C. 1 H NMR (CDCI3, 300 MHz) δ 2.84 (d, 1 H), 2.90-3.10 (dt, 2H), 3.28 (d, 1H), 3.35 (dd, 1H), 3.62 (m, 1H), 3.72- 3.97 (m, 3H), 3.80 (s, 3H), 5.13 (bd, 2H), 5.80 (m, 1H), 5.97 (s, 2H), 6.74- 6.97 (m, 5H), 7.38 (d, 2H). 25 Example 15 frans. frans-2-r4-Methoxvphenvn-4-ι / 1.3-benzodioxol-5-vn-1-fn- butylaminocarbonvlmethvl,-Pvrrolidine-3-carboxvlic acid Using the procedures described in Example 1 the title compound was prepared, m.p. 105-107 °C. 1 H NMR (CDCI3, 300 MHz) δ 0.90 (t, 30 3H), 1.30 (m, 2H), 1.45 (m, 2H), 2.80 (d, IH), 2.87-3.35 (m, 6H), 3.62 (m, 1H), 3.80 (s, 3H), 5.97 (s, 2H), 6.75-6.92 (m, 5H), 7.28 (d, 2H). Example 16 frans.frans-2-f4-Methoxvphenvn-4-(1.3-benzodioxol-5-vh-1-fN-fn-propvh-N- 35 methvlaminocarbonvlmethvlVpvrrolidine-3-carboxylic acid Using the procedures described in Example 1 the title compound was prepared as an amorphous solid. Rotational isomers are seen in the NMR. 1 H NMR (CDCI3, 300 MHz) δ 0.73, 0.84 (2t, 3H), 1.49 (m, 2H), 2.80 (dd, 1H), 2.85 (2s, 3H), 2.95-3.20 (m, 3H), 3.20-3.40 (m, 1H), 3.40 (d, 1H), 3.60 (m, 1 H), 3.79 (s, 3H), 5.93 (s, 2H), 6.73 (d, 1H), 6.86 (m, 2H), 7.03 (m, 1H), 7.32 (d, 2H). Example 17 frans.frans-2- ( 4-Methoxy p henvn-4- .3-benzodioxol-5-vπ-1-fpyrrolidin-1- ylcarbonylmethyfl-pyrrolidine-3-carboxylic acid Using the procedures described in Example 1 the title compound was prepared as an amorphous solid. 1 H NMR (CDCI3, 300 MHz) δ 1.40- 1.70 (m, 6H), 2.80 (d, 1H), 3.00 (m, 2H), 3.24-3.43 (m, 5H), 3.60 (m, 2H), 3.73 (d, 1 H), 3.80 (s, 3H), 5.95 (s, 2H), 6.74 (d, 1H), 6.80-6.90 (m, 3H), 7.04 (d, 1H), 7.30 (d, 2H). Example 18 frans.frans-2-(4-Methoxyphenvπ-4-(1.3-benzodioxol-5-yl - (isobutylaminocarbonylmethylVpyrrolidine-3-carboxylic acid Using the procedures described in Example 1 the title compound was prepared, m.p. 175-177 °C. 1 H NMR (CD 3 OD, 300 MHz) δ 0.87 (dd, 6H), 1.75 (septet, 1 H), 2.85 (d, 1H), 2.90-3.10 (m, 4H), 3.23 (d, 1H), 3.40 (m, 1H), 3.58-3.67 (m, 1H), 3.78 (s, 3H), 3.89 (d, 1H), 5.92 (s, 2H), 6.76 (d, 1H), 6.86 (dd, 1 H), 6.91 (d, 2H), 7.02 (d, 1H), 7.40 (d, 2H). Example 19 frans. frans-2-(4-MethoxyphenylV4-π.3-benzodioxol-5-yn-1- (cvclopentylaminocarbonylmethvπ-Pyrrolidine-3-carboxylic acid Using the procedures described in Example 1 the title compound was prepared, m.p. 137-139 °C. 1 H NMR (CDCI 3 . 300 MHz) δ 1.34 (m, 2H), 1.62 (m, 4H), 1.90 (m, 2H), 2.76 (d, 1H), 2.90 (t, 1H), 3.04 (dd, 1H), 3.22 (d, 1 H), 3.28 (dd, 1 H), 3.40 (m, 1 H), 3.80 (s, 3H), 4.15 (m, 1H), 5.97 (d, 2H), 6.75-6.95 (m, 5H), 7.27 (m, 2H). Example 20 frans.frans-2-(4-Methoxyphenvn-4- 1.3-benzodioxol-5-vh-1-fmorpholin-4- ylaminocarbonylmethvh-Pyrrolidine-3-carboxylic acid Using the procedures described in Example 1 the title compound was prepared as an amorphous solid. 1 H NMR (CDCI3, 300 MHz) δ 2.82 (d, 1H), 3.00 (m, 2H), 3.24 (m, 1H), 3.30-3.52 (m, 4H), 3.52-3.75 (m, 8H), 3.80 (s, 3H), 5.95 (s, 2H), 6.75 (d, 1 H), 6.84 (d, 3H), 7.00 (s, 1 H), 7.28 (d, 2H). Example 21 frans.frans^-^-Methoxv p henvn^-n.S-benzodioxol-S-vn-l-^-phenoxyethyh- Pvrrolidine-3-carboxvlic acid Using the procedures described in Example 4 the title compound was prepared as an amorphous solid. 1 H NMR (CD3OD, 300 MHz) δ 2.82 (m, 1H), 2.96 (dd, 1H), 3.13 (m, 1H), 3.32 (m, 1H), 3.51-3.70 (m, 2H), 3.77 (s, 3H), 4.00 (d, 1H), 4.07 (m, 2H), 5.91 (s, 2H), 6.72 (d, 1H), 6.80- 6.95 (m, 6H), 7.03 (d, 1H), 7.22 (dd, 2H), 7.39 (d, 2H). Example 22 frans. frans-2-f4-Methoxyphenyl -4-f1.3-benzodioxol-5-vπ-1-f2- methoxyethylaminocarbonylmethyl.-pyrrolidine-3-carboxylic acid Using the procedures described in Example 1 the title compound was prepared, m.p. 107-109 °C. 1 H NMR (CD 3 OD, 300 MHz) δ 2.82 (d, 1 H), 2.97 (q, 2H), 3.21 (d, 1H), 3.38 (m, 1H), 3.32 (s, 3H), 3.44 (m, 4H), 3.62 (m, 1H), 3.79 (s, 3H), 3.86 (d, 1H), 5.93 (s, 2H), 6.76 (d, 1 H), 6.85 (dd, 1H), 6.91 (d, 2H), 7.01 (d, 1 H), 7.38 (d, 2H). Example 23 frans. frans-2-f4-MethoxvphenvIV4- 1.3-benzodioxol-5-vI -1-ι / 2-butoxyethyn- Dvrrolidine-3-carboxvlic acid Using the procedures described in Example 4 the title compound was prepared, m.p. 53-55 °C. 1 H NMR (CDCI3, 300 MHz) δ 0.88 (t, J=7Hz, 3H), 1.32 (sextet, J=7Hz, 2H), 1.50 (pentet, J=7Hz, 2H), 2.27 (tt, J=6Hz, 6Hz, 1 H), 2.92 (q, J=10Hz, 2H), 3.35 (t, J=7Hz, 2H), 3.42-3.56 (m, 4H), 3.68 (d, J=10Hz, 1H), 3.78 (s, 3H), 5.94 (s, 2H), 6.73 (d, J=8Hz, 1 H), 6.83 (d, J=9Hz, 2H), 6.82-6.87 (m, 1H), 7.06 (d, J=2Hz, 1H), 7.32 (d, J=9Hz, 2H). MS m/e 442 (M+H) + . Examole 24 frans.frans-2-f1.3-Benzodioxol-5-yn-4-(4-methoxvphenyh-1- (propylaminocarbonvlmethvn-pvrrolidine-3-carboxylic acid Using the procedures described in Example 1 and substituting ethyl (1 ,3-benzodioxol-5-ylcarbonyl)acetate for ethyl (4- methoxybenzoyl)acetate and 4-(2-nitrovinyl)anisole for 5-(2- nitrovinyl)-1 ,3-benzodioxol-5yl afforded the title compound, m.p. 97- 99 °C. 1 H NMR (CDCI 3 , 300 MHz) δ 0.78 (t, J=7Hz, 3H), 1.39 (sextet, J=7Hz, 2H), 2.72 (d, J=16Hz, 1 H), 2.74 (t, J=10Hz, 1H), 2.80-3.10 (m, 4H), 3.26-3.38 (m, 1 H), 3.53 (m, 1H), 3.73 (s, 3H), 3.80 (d, J=10Hz, 2H), 7.80 (t, J=6Hz, 1H). MS (DCI/NH3) m/e 441 (M+H) + . Example 25 frans.frans-2-M ■3-Benzodioxol-5-ylV4-(4-methoxyphenvn-1-(2-propoxyethyn- pyrrolidine-3-carbQxyiic acid Using the procedures described in Example 5 and substituting ethyl (1 ,3-benzodioxol-5-ylcarbonyl)acetate for ethyl (4- methoxybenzoyl)acetate and 4-(2-nitrovinyl)anisole for 5-(2- nitrovinyl)-1 ,3-benzodioxol-5yl afforded the title compound, m.p. 67- 69 °C. 1 H NMR (CDCI3, 300 MHz) δ 0.89 (t, J=7Hz, 3H), 1.56 (sextet, J=7Hz, 2H), 2.33 (m, 1 H), 2.78-3.00 (m, 3H), 3.32 (t, J=7Hz, 2H), 3.45- 3.57 (m, 4H), 3.73 (m, 1H), 3.79 (s, 3H), 5.93 (s, 2H), 6.22 (d, J=8Hz, 1H), 6.85 (d, J=8Hz, 3H), 6.98 (s, 1H), 7.37 (d, J=8Hz, 2H). MS (DCI/NH3) m/e 428 (M+H) + . Example 26 frans.frans-2-(1.3-Benzodioxol-5-vn-4-(4-methoxyphenvn-1-r2-f2- methoxyethoxvtethvm-pvrrolidine-3-carboxvlic acid Using the procedures described in Example 4 and substituting the starting materials described in Example 25 and using 2-(2- methoxyethoxy)ethylbromide to alkylate the pyrrolidine nitrogen afforded the title compound, m.p. 85-86 °C. 1 H NMR (CD30D, 300 MHz) δ 3.18-3.90 (m, 15H), 3.79 (s, 3H), 4.57 (d, J=10Hz, 1 H), 6.02 (s, 2H), 6.91 (d, J=8Hz, 1H), 6.95 (d, J=9Hz, 2H), 7.06 (dd, J=8Hz, 1H), 7.12 (dd, J=1Hz, 1H), 7.37 (d, J=9Hz, 2H). MS (DCI/NH3) m/e 444 (M+H) + . Example 27 frans. frans^-π.S-Benzodioxol-S-ylM-^-methoxvphenvn-l-fbutoxyethyn- pyrrolidine-3-carboxvlic acid Using the procedures described in Example 4, substituting the 5 starting materials described in Example 25 and using 2- ethoxyethylbromide to aikylate the pyrrolidine nitrogen afforded the title compound, m.p. 54-56 °C. 1 H NMR (CDCI 3> 300 MHz) δ 0.89 (t, J- 7Hz, 3H), 1.44 (sextet, J=7Hz, 2H), 1.52 (pentet, J=7Hz, 2H), 2.40 (m, 1H), 2.74-2.98 (m, 3H), 3.46 (t, J=7Hz, 2H), 3.42-3.56 (m, 4H), 3.68 (d, ι o J=10Hz, 1H), 3.80 (s, 3H), 5.93 (dd, J=6Hz, 1Hz, 2H), 6.72 (d, J=8Hz, 1H), 6.74 (dd, J=9Hz, 3H), 6.96 (s, 1H), 7.36 (d, J=9Hz, 2H). Example 28 trans. frans-2-(4-Methoxyphenyh-4-( 1.4-benzodioxan-6-yn- 1 - 15 rpropylaminocarbonvlmethyn-pyrrolidine-3-carboxvlic acid Using the procedures described in Example 1 and substituting 6- (2-nitrovinyl)-1 ,4-benzodioxane for 5-(2-nitrovinyl)-1 ,3-benzodioxole afforded the title compound, m.p. 80-81 °C. 1 H NMR (CDCI 3 , 300 MHz) δ 0.89 (t, J-7Hz, 3H), 1.49 (sextet, J=7Hz, 2H), 2.78 (d, J=16Hz, 1 H), 2.92 0 (t, J=10Hz, 1H), 3.05-3.43 (m, 5H), 3.24 (d, J=16Hz, 1H), 3.52-3.62 (m, 1H), 3.80 (s, 3H), 3.80 (t, J=10Hz, 1H), 4.27 (s, 4H), 6.74-6.93 (m, 5H), 7.29 (d, J=9Hz, 2H). MS (DCI/NH3) m/e 455 (M+H) + . Example 29 5 frans. fraπs-2-r4-Methoxyphenyn-4-π.4-benzodioxan-6-vn-1-fN-methyl-N- proρylaminocarbonylmethylϊ-pyrrolidine-3-carboxylic acid Using the procedures described in Example 1 , substituting 6-(2- nitrovinyl)-1 ,4-benzodioxane for 5-(2-nitrovinyl)-1 ,3-benzodioxole and alkylating the pyrrolidine nitrogen with N-methyl-N-propyl 0 bromoacetamide afforded the title compound, m.p. 74-76 °C. Rotational isomers are seen in the NMR. 1 H NMR (CDCI 3 , 300 MHz) δ 0.73, 0.83 (2t, J=7Hz, 3H), 1.48 (m, 2H), 2.78 (dd, 1 H), 2.85 (2s, 3H), 2.96-3.15 (m, 3H), 3.27-3.42 (m, 3H), 3.52-3.60 (m, 1H), 3.75 (d, 1H), 3.78 (s, 3H), 4.22 (s, 4H), 6.80-6.98 (m, 5H), 7.32 (d, 2H). MS (DCI/NH3) 5 m/e 469 (M+H) + . Example 3Q frans.frans-2- ( 4-Methoxvphenvn-4-f1.3-benzodioxol-5-vn-1-rN-methyl-N- butylaminocarbonylmethyh-pvrrolidine-3-carboxyIic acid Using the procedures described in Example 1 , the title compound was prepared. Rotational isomers are seen in the NMR. 1 H NMR (CD3OD, 300 MHz) δ 0.86 (2t, 3H), 1.04-1.50 (m, 4H), 2.85 (2s, 3H), 2.93-3.20 (m, 4H), 3.40 (m, 2H), 3.52 (dd, 1H), 3.60 (m, 1H), 3.80 (s, 3H), 3.85 (m, 1H), 5.91 (s, 2H), 6.74 (d, 1H), 6.83-6.95 (m, 3H), 7.03 (dd, 1H), 7.35 (dd, 2H). Example 31 frans. frans-2-f4-Methoxy-2-methoxymethoxy p henvn-4-f1.3-benzodioxol-5-vn-1-rN- methvl-N-butvlaminocarbonylmethvn-pyrrolidine-3-carboxylic acid Example 31 A Ethyl 2-ι , 4-methoxy-2-methoxymethoxvphenvl-4-f1.3-benzodioxol-5-yn-pyrrolidine- 3-carbpχyiate) Using the procedures described in Examples 1A and 1B and substituting ethyl (4-methoxy-2-methoxymethoxybenzoyl)acetate for ethyl (4-methoxybenzoyl)acetate afforded ethyl 2-(4-methoxy-2- methoxymethoxyphenyl)-4-(1 ,3-benzodioxol-5-yl)-4,5-dihydro-3H- pyrrole-3-carboxylate. The above dihydro pyrrole carboxylate (3.0 g, 7.0 mmol) was dissolved in 20 mL of methanol, treated with 500 mg of 10% Pd/C and placed under hydrogen atmosphere for 32 hours. The catalyst was removed by filtration and the filtrate was concentrated under reduced pressure and chromatographed on silica gel eluting with ethyl acetate to afford the title compound (1.9 g, 63%) as the cis-cis isomer. Example 31 B frans. frans-2- 4-Methoxy-2-methoxymethoxyphenylV4-M .3-benzodioxol-5-yn-1-/N- methyl-N-butylaminocarbonylmethylVpyrroiidine-3-carboxylic acid The compound resulting from Example 31 A was epimerized by the procedure described in Example 6A. The resulting trans.trans compound (100 mg, 0.23 mmol) was then reacted by the procedures described in Example 1D substituting N-methyl-N-butyl bromoacetamide for N- propyl bromoacetamide to give the title compound (75 mg, 62%). m.p. 65-67 °C. Rotational isomers are seen in the NMR. 1 H NMR (CDCI3, 300 MHz) δ 0.64, 0.68 (2t, J=7Hz, 3H), 1.14, 1.12 (2 sextet, J=7Hz, 2H), 1.40- 1.48 (m, 2H), 2.86, 2.89 (2s, 3H), 2.95-3.42 (m, 6H), 3.50 (s, 3H), 3.43- 3.65 (m, 2H), 3.78 (s, 3H), 4.30 (t, J=7Hz, 1H), 5.09 (q, J=7Hz, 2H), 5.92 (s, 2H), 6.55 (dd, J=3Hz, 1H), 6.68 (s, 1H), 6.72 (s, 1H), 6.85 (2t, J=1 Hz, 1 H), 7.04 (t, J=1Hz, 1H), 7.42 (dd, J=3Hz, 1H). Example 32 frans. frans-2-f4-Methoxvphenvn-4-M.3-benzodioxol-5-yn-1-f3-ethoxypropyn- pyrrolidin-5-one-3-carboxylic acid Example 32A Ethyl 2-f4-methoxvbenzovn-3-carbomethoxv-1.3-benzodioxole-5-propionate To ethyl (4-methoxybenzoyl)acetate (4.44 g, 0.02 mmol) dissolved in 20 L of anhydrous THF was added in portions 480 mg of NaH. The mixture was stirred for 30 minutes under nitrogen at ambient temperature. Methyl (1 ,3-benzodioxol-5-yl) bromoacetate (5.46 g, 0.02 mol) in 5 mL of THF was added. The mixture was stirred overnight at ambient temperature, diluted with 200 mL of EtOAc, and washed with water and brine. The organic phase was dried over sodium sulfate and concentrated in vacuo to afford the title compound (7.67 g, 92%) which was used without further purification. Example 32B Ethyl 1-f3-ethoxypropyπ-2-f4-methoxyphenvπ-4-π .3-benzodioxol-5-vh-4.5-dihvdro- 5-OXO-1 H-pyrrole-3-carboxylate A mixture of the compound resulting from Example 32A (700 mg, 1.69 mmol), 3-ethoxypropylamine (348 mg, 3.38 mmol) and 1 mL of acetic acid in a sealed tube was heated for 18 hours at 125 °C. After cooling the contents of the tube to ambient temperature, 5 mL of water was added and the mixture extracted with ethyl acetate (2x100 mL). The combined organic extracts were washed with saturated sodium bicarbonate solution, water and brine, dried over sodium sulfate and concentrated under reduced pressure. The residue obtained was chromatographed on silica gel eluting with 3:2 hexane-ethyl acetate to give 330 mg (42%) of the title compound. Exampie 32C Ethyl 1 - 3-ethoxvpropvn-2- 4-methoxvphenvlV4-π .3-benzodioxQl-5-yn-pyrrolidin-5- one-3-carboxylate The compound resulting from Example 32B (300 mg, 0.64 mmol) in 15 mL of methanol was reduced with 100 mg of 10% Pd/C under hydrogen for 3 hours at ambient temperature. The catalyst was removed by filtration and the filtrate was concentrated under reduced pressure to give the title compound. Example 32D frans.frans-2-f4-Methoxv p henvn-4-(1.3-benzodioxol-5-vn-1 -ι3-ethoxypropyh- pvrrolidin-5-one-3-carboxylic acid To the compound resulting from Example 32C (100 mg, 0.21 mmol) dissolved in 1 mL of ethanol was added 3 drops of a solution of 21% sodium ethoxide in ethanol. The mixture was heated to 70-80 °C for 3 hours, and then a solution of sodium hydroxide (100 mg) in 1 mL of water was added and heating was continued for 1 additional hour. The reaction mixture was cooled to ambient temperature, the ethanol was removed under reduced pressure, and water was added to the residue which was washed with ether. The aqueous layer was neutralized with 3 M HCl and allowed to stand overnight. The white crystalline solid was collected by filtration to give the title compound (60 mg, 64%). m.p. 134-140 °C. " Η NMR (DMSO-d 6 , 300 MHz) δ 1.04 (t, J=7Hz, 3H), 1.55 (sextet, J=7Hz, 2H), 2.48-2.56 (m, 1 H), 2.93 (dd, J=9Hz, 1 H), 3.25 (t, J=7Hz, 2H), 3.28-3.40 (m, 2H), 3.48-3.57 (m, 1 H), 3.78 (s, 3H), 3.88 (d, J=10Hz, 1 H), 4.72 (d, J=10Hz, 1 H), 6.02 (s, 2H), 6.74 (dd, J=8Hz, 1Hz, 1H), 6.87 (d, J=8Hz, 2H), 6.98 (d, J=8Hz, 2H), 7.38 (d, J=8Hz, 2H). MS (DCI/NH3) m/e 442 (M+H) + . Example 33 frans.frans-2-f4-MethoxyphenvlV4-n .3-benzodioxol-5-yn-1-(3-methoxybenzyn- pyrroIidin-5-one-3-carboxylic acid Following the procedures described in Example 32 and substituting 3-methoxybenzylamine for 3-ethoxypropylamine afforded the title compound (123 mg, 65%). m.p. 150-152 °C. 1 H NMR (CD3OD, 300 MHz) δ 2.96 (dd, J=8Hz, 10Hz, 1 H), 3.72 (s, 3H), 3.80 (s, 3H), 4.06 (d, J=10Hz, 1 H), 4.58 (d, J=8Hz, 1H), 4.92 (q, J=16Hz, 2H), 5.92 (s, 2H), 6.55-6.63 (m, 2H), 6.82 (d, J=8Hz, 4H), 6.94 (d, J=8Hz, 2H), 7.15-7.22 (m, 3H). MS (DCI/NH3) m/e 475 (M+H) + . Example 34 frans. frans^-M-Methoxv p henvl -fl .S-benzodioxol-δ-vn-l-rN.N- diisoamylaminocarbonylmethylV p yrrolidine-3carboxylic acid The title compound was prepared as an amorphous solid using the procedures described in Example 1. 1 H NMR (CDCI3, 300 MHz) δ 0.70 -0.90 (m, 12H), 1.10-1.60 (m, 10H), 2.75 (d, J=13Hz, 1 H), 2.90-3.10 (m, 4H), 3.15 - 3.30 (m, 2H), 3.40 (d, J=10Hz, 1H), 3.40 - 3.52 (m, 2H), 3.55 - 3.62 (m, 1 H), 3.75 (d, J=12 Hz, 1 H), 3.79 (s, 3H), 5.93 (dd, J =1 Hz, 3 Hz, 2H), 6.72 (d, J=8Hz, 1 H), 6.82-6.90 (m, 3H), 7.03 (d, J=2Hz, 1 H), 7.30 (d, J=9Hz, 2H). Example 35 frans.frans-2-N-i-Methoxyphenyl -π .3-benzodioxol-5-ylV1-(N.N- dipentylaminocarbonylmethvπ-pyrrolidine-3-carboxylic acid The title compound was prepared as an amorphous solid using the procedures described in Example 1. 1 H NMR (CDCI3, 300 MHz) δ 0.82 (t, J = 7Hz, 6H), 0.95-1.03 (m, 2H), 1.10-1.30 (m, 8H), 1.40-1.51 (m, 2H), 2.72 (d, J=13Hz, 1 H), 2.90-3.08 (m, 4H), 3.25-3.50 (m, 3H), 3.37 (d, J=13Hz, 1 H), 3.52-3,60 (m, 1 H), 3.70 ( J=10Hz, 1 H), 3.75 (s, 3H), 5.92 (dd, J=2Hz, 5Hz, 2H), 6.72 (d, J=8Hz, 1 H), 6.80-6.88 (m, 3H), 7.03 (d, J=2Hz, 1H), 7.30 (d, J=9Hz, 2H). Example 36 methoxyethvDaminocarbonylmethyh-pyrrolidine-3-carboxylic acid The title compound was prepared using the procedures described in Example 1. m.p. 120-122 °C. 1 H NMR (CDCI3, 300 MHz) δ 2.82 (d, J=13, 1H), 2.94-3.08 (m, 2H), 3.12 (s, 3H), 3.23 (s, 3H), 3.20-3.70 (m, 1 1 H), 3.73 (d, J=10Hz, 1 H), 3.79 (s, 3H), 5.92 (dd, J= 2Hz, 2Hz, 2H), 6.72 (d, J=8Hz, 1 H), 6.80-6.90 (m, 3H), 7.04 (d, J=2Hz, 1 H), 7.30 (d, J=9Hz, 2H). Exam le 37 frans.frans-2-(4-Methoxyphenv[V4-n .3-benzodioxol-5-vn-1-ι , 2-hexynvn-pyrroliriinft- 3-carboxylic acid Using the procedures described in Example 4, 200 mg. of the pure 5 trans.trans isomer, the compound resulting from Example 6A was reacted with 109 mg of 1-bromo-2-hexyne, prepared by the method described in Perkin I, , 2004 (1987), for 1 hour at 55 °C, to give 226 mg of the intermediate ester. The ester was hydrolyzed using NaOH in ethanol-water for 3 hours at room temperature to give 175 mg of the ι o title compound. 1 H NMR (CDCI 3 , 300 MHz) δ 1.00 (t, J=7Hz, 3H), 1.54 (m, 2H), 2.14-2.22 (m, 2H), 2.96 (dd, J=7Hz, 13Hz, 1 H), 3.07 (dd, J=18Hz, 2Hz, 1H), 3.15 (dd, J=9Hz, 2Hz, 1H), 3.26 (t, J=9Hz, 1H), 3.36 (dd, J = 18 Hz, 2Hz, 1 H), 3.47-3.55 (m, 1 H), 3.79 (s, 3H), 3.88 (d, J=9Hz, 1 H), 5.95 (s, 2H), 6.72 (d, J=8Hz, 1H), 6.80-6.88 (m, 3H), 7.03 (d, J=2Hz, 1 H), 7.22 15 (d, J=9Hz, 2H). Example 38 frans. frans-2-f4-Methoxyphenyl)-4-f1.3-benzodioxol-5-vn-1-fN-cvclopropylmethyl- N-propvlaminocarbonvlmethvlVpyrrolidine-3-carboxylic acid 20 The title compound was prepared using the procedures described in Example 1. m.p. 167-169 °C. Rotational isomers were seen in the NMR. 1 H NMR (CDCI3, 300 MHz) δ -0.1 (m), 0.05 (m), 0.12-0.25 (m), 0.32- 0.51 (m), 0.67 and 0.74 (2 triplets, 3H), 0.90-1.00 (m), 1.20-1.55 (m), 2.72 (d, J=13Hz, 1 H), 2.85-3.29 (m, 4H), 3.30-3.50 (m, 3H), 3.52-3.62 25 (m, 1 H), 3.65-3.73 (2 doublets, J=10Hz, 2Hz, 1 H), 3.78 (s, 3H), 5.95 (2 singlets, 2H), 6.72 (2 doublets, 2H), 6.80-6.90 (m, 3H), 7.00 and 7.05 (2 doublets, J=9Hz, 2H). Example 39 30 frans.frans-2-f4-Methoxyphenyl)-4-π .3-benzodioxol-5-yn-1-fN-methyl-N- pentylaminocarbonylmethyn-Pvrrolidine-3-carboxylic acid The title compound was prepared as an amorphous solid using the procedures described in Example 1. Rotational isomers were seen in the NMR. 1 H NMR (CDCI3, 300 MHz) δ 0.85 (t, J=7Hz, 3H), 1.00-1.08 (m), 35 1.13-1.32 (m), 1.35-1 ,50 (m), 2.72-2.82 (2 doublets, J=13Hz, 1 H), 2.83 and 2.86 (2 singlets, 3H), 2.92-3.20 (m, 3H), 3.22-3.45 (m, 3H), 3.52- 3.62 (m, 1H), 3.72 (2 doublets, 1H), 3.75 and 3.76 (2 singlets, 3H), 5.92 (2 singlets, 2H), 6.72 (d, J=8Hz, 1 H), 6.80-6.87 (m, 3H), 7.03 (2 doublets, J=2Hz, 1 H), 7.30 (d, J=9Hz, 2H). Example 4Q frans.frans-2-t " 4-Methoxvphenvn-4-(1.3-benzodioxol-5-vn-1-fN.N- diisobutylaminocarbonvlmethvn-pyrrolidine-3-carboxylic acid The title compound was prepared using the procedures described in Example 1. m.p. 141-143 °C. 1 H NMR (CDCI 3 , 300 MHz) δ 0.54 (d, J^Hz, 3H), 0.70-0.90 (3 doublets, J=7Hz, 9H), 1.60-1.75 (m, 1H), 1.90- 2.02 (m, 1 H), 2.67 (d, J=13Hz, 1H), 2.70 (d, J=13Hz, 1 H), 2.84 (dd, J=6Hz, 15Hz, 1 H), 2.96-3.06 (m, 2H), 3.20 (dd, J=9Hz, 15Hz, 1 H), 3.35 (dd, J=2Hz, 10Hz, 1 H), 3.44-3.60 (m, 4H), 3.70 (d, J=9Hz, 1 H), 3.79 (s, 3H), 5.94 (dd, J=2Hz, 2Hz, 2H), 6.72 (d, J=9Hz, 1H), 6.82-6.90 (m, 3H), 7.03 (d, J=2Hz, 1H), 7.31 (d, J=9Hz, 2H). Example 41 frans. frans-2-f4-Methoxyphenyn-4-π .3-benzodioxol-5-vπ-1-fN-methvl-N-f2- propynvham inocarbonvlmethyn-Pvrrolidine-3-carboxylic acid The title compound was prepared as an amorphous solid using the procedures described in Example 1. Rotational isomers were seen in the NMR. 1 H NMR (CDCI3, 300 MHz) δ 2.09 and 2.32 (2 triplets, J=2Hz, 1 H), 2.80-3.10 (m, 3H), 2.90 and 2.99 (2 singlets, 3H), 3.35-3.50 (m, 2H), 3.52-3.62 (m, 1 H), 3.78 (s, 3H), 4.03 (d, J=13Hz, 1 H), 4.00-4.30 (m, 3H), 5.93 (s, 2H), 6.72 (2 doublets, J=8Hz, 1H), 6.80-6.90 (m, 3H), 7.02 and 7.11 (2 doublets, J = 2Hz, 1 H), 7.30 (2 doublets, J=9Hz, 2H). Example 42 hexynaminocarbonvlmethvn-Pvrrolidine-3-carboxvlic acid The title compound was prepared as an amorphous solid using the procedures described in Example 1. 1 H NMR (CDCI3, 300 MHz) δ 0.85 (2 triplets, J=7Hz, 3H), 1.00-1.50 (m, 8H), 2.72-2.82 (2 doublets, J=13Hz, 1 H), 2.81 and 2.86 (2 singlets, 3H), 2.92-3.20 (m, 3H), 3.22-3.45 (m, 3H), 3.52-3.62 (m, 1 H), 3.72 (2 doublets, 1 H), 3.75 and 3.76 (2 singlets 3H), 5.94 (2 singlets, 2H), 6.72 (d, J=8Hz, 1 H), 6.80-6.87 (m, 3H), 7.03 (2 doublets, J=2Hz, 1 H), 7.30 (d, J=9Hz, 1 H). Exampie 43 frans.frans-2-(4-Methoxvphenvh-4-π .3-benzodioxol-5-vh-1-f/V Λ/- d/D jf arn/nocar p onv/mef ή v/>-ρyrrolidine-3-carboxylic acid The title compound was prepared using the procedures described in Example 1. m.p. 123-125 °C. 1 H NMR (CDCI 3 , 300 MHz) δ 0.79 (t, J=7Hz, 3H), 0.85 (t, J=7Hz, 3H), 1.00-1.50 (m, 8H), 2.74 (d, J=13Hz, 1 H), 2.90-3.09 (m, 4H), 3.23-3.50 (m, 3H), 3.38 (d, J=13Hz, 1 H), 3.52-3.62 (m, 1H), 3.75 (d, J=10 Hz, 1H), 3.78 (s, 3H), 5.93 (dd, J=2Hz, 4Hz), 6.71 (d, J=8Hz, 1 H), 6.81-6.89 (m, 3H), 7.03 (d, J=2Hz, 1 H), 7.30 (d, J=9 Hz, 2H). MS (DCI/NH3) m/e 511 (M+H) + . Anal calcd for C29H38N2O6: C, 68.21 ; H, 7.50; N, 5.49. Found: C, 68.07; H, 7.47; N, 5.40. Example 44 frans. frans-2-(4-Methoxvphenvh-4-n .3-benzodioxol-5-ylV1-rN.N- diethylaminocarbonylmethyl)-pyrrolidine-3-carboxylic acid The title compound was prepared using the procedures described in Example 1. m.p. 132-134 °C. 1 H NMR (CDCI3, 300 MHz) δ 0.98 (t, J=7Hz, 3H), 1.06 (t, J=7Hz, 3H), 2.78 (d, J=13 Hz, 1 H), 2.95-3.20 (m, 4H), 3.30-3.50 (m, 4H), 3.55-3.65 (m, 1H), 3.76 (d, J=12 Hz, 1 H), 3.79 (s, 3H), 5.93 (s, 2H), 6.72 (d, J=8Hz, 1 H), 6.80-6.90 (m, 3H), 7.02 (d, J=2Hz, 1H), 7.32 (d, J=9Hz, 2H). Example 45 frans.frans-2-(4-MethoxyphenylV4-(1.3-benzodioxol-5-vn-1-(N-methyl-N- phenylaminocarbonylmethyl)-pyrrolidine-3-carboxylic acid The title compound was prepared as an amorphous solid using the procedures described in Example 1. H NMR (CD3OD, 300 MHz) δ 2.75- 2.85 (m, 2H), 3.05-3.13 (m, 1H), 3.18 (s, 3H), 3.40-3.58 (m, 2H), 3.78 (s, 3H), 3.88 (d, J=12Hz, 1 H), 5.92 (s, 2H), 6.72 (d, J=8Hz, 1 H), 6.75- 6.85 (m, 3H), 7.00-7.12 ( , 5H), 7.82-7.92 (m, 3H). Example 46 fran≤.frans-2-(4-Methoxvphenvn-4-f1.3-benzodioxol-5-vn-1-fN-methyl-N- cyclohexyIaminocarbonylmethyh-pyrrolidine-3-carboxvlic acid The title compound was prepared as an amorphous solid using the procedures described in Example 1. Rotational isomers were seen in the NMR. 1 H NMR (CD3OD, 300 MHz) δ 1.00-1.85 (m. 10H), 2.72 and 2.78 (2 singlets, 3H), 2.75-2.82 (2 doublets, J=12Hz, 1 H), 2.96-3.22 (m, 3H), 3.40-3.65 (m, 3H), 3.68 and 3.82 (2 doublets, J=10Hz, 1 H), 3.77 and 3.78 (2 singlets, 3H), 5.92 (s, 2H), 6.72 (2 doublets, J=8Hz, 1 H), 6.82-6.88 (m, 3H), 7.02 (2 doublets, J=2Hz, 1 H), 7.30-7.40 (2 doublets, J=9Hz, 5 2H). Example 7 frans.frans^-M-Methoxyphenyπ^-ri .S-benzodioxol-S-ylVI-fN.N-di/n- propyham inocarbonylmethvπ-pyrrolidine-3-carboxylic acid ι o The title compound was prepared using the procedures described in Example 1. m.p. 170-172 °C. 1 H NMR (CDCI3, 300 MHz) δ 0.69 (t, J=7Hz, 3H), 0.85 (t, J=7Hz, 3H), 1.20-1.55 (m, 4H), 2.72 (d, J=13Hz, 1 H), 2.90-3.10 (m, 4H), 3.25-3.47 (m, 4H), 3.35-3.62 (m, 1 H), 3.72 (d, J=9Hz, 1 H), 3.79 (s, 3H), 5.94 (s, 2H), 6.72 (d, d, J=8Hz, 1 H), 6.80-6.90 (m, 3H), 15 7.02 (d, J=2Hz, 1 H), 7.30 (d, J=9Hz, 2H). Example 49 frans.frans-2-r4-MethoxvphenyU-4-n .3-benzodioxol-5-vl -1- N-methvl-N- isobutvlaminocarbonvlmethvn-Pvrrolidine-3-carboxvlic acid 20 The title compound was prepared as an amorphous solid using the procedures described in Example 1. Rotational isomers were seen in the NMR. 1 H NMR (CD3OD, 300 MHz) δ 0.65-0.85 (4 doublets, J=7Hz, 6H), 1.75-1.95 (m, 1 H), 2.80 and 2.90 (2 singlets, 3H), 2.90-3.10 (m, 4H), 3.10-3.65 (m, 4H), 3.74 9S, 3H), 3.81 and 3,88 (2 doublets, J=10Hz, 1 H), 25 5.93 (s, 2H), 6.72 (d, J=8Hz, 1 H), 6.80-6.90 (m, 3H), 7.02 (2 doublets, J=2Hz, 1 H), 7.80-7.90 (2 doublets, J=9Hz, 2H). Example 49 Alternate Preoration of 30 Ethvl 2-f4-methoxvbenzovn-4-nitromethvl-3-n .3-benzodioxole-5-vnbutvrate Example 49A E-2-ι , 3.4-Methylenedioxyphenvn-1-nitroethene To a stirred solution of piperonal (75g, 500 mmol) in methanol 35 (120 mL) at 10 °C was added nitromethane (27.1 mL, 500 mmol, 1 eq) followed by the dropwise addition of sodium hydroxide (21 g, 525 mmol, 1.05 eq) in sufficient water to achieve a total volume of 50 mL while maintaining the temperature between 10-15 °C. The reaction mixture became cloudy, tuming to a thick paste. The mixture was stirred for 30 minutes upon completion of the addition, and the mixture was then diluted with ice-water (-350 mL) maintaining the temperature below 5 5 °C, until solution was achieved. The resultant solution was poured in a narrow stream (such that it just failed to break into drops) into a rapidly stirred solution of 36% hydrochloric acid (100 L) in water (150 mL). A yellow solid precipitated (nitrostyrene), and this was collected by filtration, washed with water (1.5 L) until the filtrate was ι o neutral. The filter cake was air dried and then recrystallized from hot ethanol (3 L) to yield E-2-(3,4-methylenedioxy)-nitrostyrene as yellow needles (53 g, 55%). 1 H NMR (300MHz, CDCI3) δ 7.94 (1H, d, J=13.5HZ)L, 7.47 (1H, d, J=13.5Hz), 7.09 (1H, dd, J=7.5&2Hz), 7.01 (1H, d, J=2Hz), 6.87 (1H, d, J=7.5Hz), 6.06 (2H, s). MS (DCI/NH3) m/e 194 (M+H) + , 211 15 (M+H+NH 3 ) + . Example 49B Ethyl 2-(4-methoxvphenvnoxo-4-nitro-3-f3.4-methvlenedioxvphenvnbutvrate 20 To a stirred solution of the nitrostyrene resulting from Example 49A (14.17 g, 73.34 mmol, 1.2 eq) in a mixture of propan-2-ol (75 mL) and tetrahydrofuran (175 mL) at room temperature was added successively a solution of ethyl (4-methoxybenzoyl)acetate (11.5 g, 51.7 mmol) in THF (50 mL) followed by 1 ,8-diazabicyclo[5,4,0]undec-7- 25 ene (DBU) (0.45 mL, 3.0 mmol, 0.05 eq). The resultant mixture was stirred at room temperature for 1 hour, then additional DBU (0.45 mL, 3.0 mmol, 0.05 eq) was added. The mixture was stirred a further 1 hour, then the volatiles were removed in vacuo and the residue purified by flash chromatography on 500 g silica gel, eluting with 20% ethyl 30 acetate-hexanes changing to 25% ethyl acetate-hexanes as the product eluted. The solvents were removed in vacuo to yield the nitroketoester (19.36 g, 76%) as a viscous oil. Diastereomers were seen in the NMR. 1H NMR (300 MHz, CDCI 3 ,) δ 8.06 (2H, d, J=9Hz), 7.89 (2H, d, J=9Hz), 6.96 (2H, d, J=9Hz), 6.91 (2H, d, J=9Hz), 6.77 (1 H, dd, J=9Hz,3Hz), 6.73 (1H, d, 35 J=9Hz), 6.65 (1 H, d, J=3Hz), 5.95 (2H, s), 5.89 (1H, d, J=4Hz), 5.88 (1H, d, J=4Hz), 4.90-4.60 (3H, m), 4.39 (1H, m), 4.18 (2H, q, J=7Hz), 3.94 (2H, m), 3.80 (3H, s), 3.78 (3H, s), 1.19 (3H, t, J=7Hz), 0.99 (3H, t, J=7Hz), MS (DCI/NH3) m/e 416 (M+H) + , 433 (M+H+NH 3 ) + . Example 5Q frans.frans-2-f4-Methoxyphenvl 4-M .3-benzodioxol-5-vn-1-t ' t- butyloxycarbonylmethvn-Pyrrolidine-3-carboxylic acid To a stirred solution of the compound resulting from Example 1C (100 mg, 0.27 mmol) in acetonitrile (2 mL) was added successively diisopropylethylamine (70 μL, 0.40 mmol, 1.5 eq) and t-butyl bromoacetate (48 μL, 0.29 mmol, 1.1 eq). The mixture was stirred 2 hours, then the solvent was removed in vacuo to yield the crude diester. To a stirred solution of the diester in ethanol (1 mL) at room temperature was added 50% w/w sodium hydroxide (300 mg, 3.75mmol) in water. The mixture was stirred 2 hours, then the volatiles were removed in vacuo. The residue was dissolved in water (5 mL), and the solution was washed with ether. The aqueous phase was acidified with acetic acid (300 μL), and then extracted with ethyl acetate (2x). The combined organic extracts were dried (Na2S04), filtered, and concentrated to yield the title compound (74 mg, 60%) as a white solid. 1H NMR (300 MHz, CDCI3) δ 7.36 (2H, d, J=8Hz), 7.13 (1 H, d, J=3Hz), 6.90 (1 H, dt, J=3Hz, 8Hz), 6.88 (2H, d, J=8Hz), 6.76 (1 H, d, J=8Hz), 5.96 (2H, s), 3.96 (1 H, d, J=9Hz), 3.81 (3H, s), 3.58 (1 H, ddd, J=12, 10Hz,3Hz), 3.52 (1H, dd, J=9Hz,3Hz), 3.32 (1 H, d, J=17Hz), 3.08 (1 H, t, J=10Hz), 2.92 (1 H, dd, J=9Hz,7Hz), 2.83 (1 H, d, J=17Hz). MS (DCI/NH3) m/e 456 (M+H) + . Anal calc for C29H29NO7 • 0.3 H 2 0: C, 65.07; H, 6.48; N, 3.04. Found: C, 65.02; H, 6.42; N, 2.93. Example 51 frans. frans-2-f4-Methoxyphenvπ-4-f1-naphthvπ-1-(N-methyl-N- propyπaminocarbonylmethvπ-pyrrolidine-3-carboxylic acid The title compound was prepared by the procedures described in Examples 1 and 49 substituting naphthalene-1 -carboxaldehyde for piperonyl in Example 49A. Rotational isomers are seen in the NMR. 1 H NMR (300 MHz, CDCI3) δ 8.29 (1 H, bd, J=8Hz), 7.86 (2H, d, J=8Hz),7.75 (1H, d, J=8Hz), 7.49 (3H, m), 7.34 (2H, dd, J=3Hz,9Hz), 6.83 (2H, dd, J=9Hz,2Hz), 4.50 (1 H, m), 3.94 (1 H, dd, J=9Hz,2Hz), 3.78 (3H, s), 3.65 (1H, m), 3.49 (1H, d, J=14Hz), 3.40-2.93 (5H, m), 2.91 , 2.83 (3H, s), 1.48 (2H, sept, J=7Hz), 0.83, 0.77 (3H, t, J=7Hz). MS (DCI/NH3) m e 461 (M+H) + . Anal calcd for C29H29NO7 • 0.5 HOAc: C, 71.00; H, 6.99; N, 5.71. Found: C, 70.95; H, 7.00; N, 5.46. Example 52 fraπs.frans-2-f4-Methoxv p henvn-4- ( 2.3-dihvdrobenzofuran-5-vh-1-fN-methyl-N- propvnaminocarbonylmethvn-Pvrrolidine-3-carboxylic acid Example 52A 2.3-Dihvdrobenzofuran-5-carboxaldehvde To a stirred solution of α,α-dichloromethyl methyl ether (2.15 g, 19 mmol, 1.35 eq) in methylene chloride (30 mL) at -40 °C was added successively stannic chloride (1.65 g, 17 mmol, 1.2 eq) and 15 minutes later, a solution of 2,3-dihydrobenzofuran (1.68 g, 14 mmol) in CH 2 CI2 (5 mL) maintaining the temperature at or below -35 °C. The mixture was warmed to 0 °C, stirred 1 hour, then poured into ice- water, and stirred a further 30 minutes. The mixture was diluted with ether, and the phases separated. The organic phase was concentrated in vacuo, and the residue purified by vacuum distillation to yield the title compound (1.25 g, 60%) as a colorless liquid, b.p. 119-121 °C at 0.3 mm Hg. Example 52B trans. frans-2-f4-MethoxyphenylV4-f2.3-dihvdrobenzofυran-5-vlV1-fN-methvl-N- propynaminocarbonylmethvn-pyrrolidine-3-carboxvlic acid The title compound was prepared by the procedures described in Examples 1 and 49 substituting the compound resulting from Example 52A for piperonal in Example 49A. Rotational isomers are seen in the NMR. 1 H NMR (300 MHz, CDCI3) δ 7.33 (1H, d, J=8Hz), 7.28 (1H, m), 7.19 (1 H, m), 6.87 (1H, d, J=8Hz), 6.73 (1 H, d, J=8Hz), 4.56 (1 H, t, J=8Hz), 3.83 (1H, d, J=10Hz), 3.80 (3H, s), 3.63 (1H, m), 3.4-3.0 (9H, m), 2.87, 2.84 (3H, s), 1.51 (2H, septet, J=7Hz), 0.88, 0.78 (3H, t, J=7Hz). MS (DCI/NH3) m/e 453 (M+H) + . Anal calc for C26H32N2O5 • 0.25 H 2 0: C, 68.33; H, 7.17; N, 6.13. Found: C, 68.60; H, 6.88; N, 5.80. Examole 53 frans.frans-2.4-Bis(4-methoxyphenyn-1-rN-methvl-N-propynaminocarbonylmethyn- pyrrolidine-3-carboxvlic acid The title compound was prepared by the procedures described in Examples 1 and 49 substituting 4-methoxybenzaldehyde for piperonal in Example 49A. Rotational isomers are seen in the NMR. 1 H NMR (300 MHz, CDCI 3 ) δ 7.37 (2H, d, J=7.5 Hz), 7.32 (2H, d, J=7.5 Hz), 6.86 (4H, m), 3.83 (1 H, m), 3.81 (3H, s), 3.79 (3H, s), 3.64 (1 H, m), 3.48-2.97 (6H, m), 2.87, 2.83 (3H, s), 2.85 (1 H, m), 1.45 (2H, m), 0.84, 0.74 (3H, t, J=7.5 Hz). MS (DCI/NH3) m/e 441 (M+H) + . Anal calc for C-25H32N2O5 • 0.5 H 2 0: C, 66.80; H, 7.40; N, 6.23. Found: C, 67.15; H, 7.31 ; N, 6.00. Example 54 frans.frans-2-(4-Methoxyphenyn-4-r3.4-dimethoxvphenvn-1-t ' N-methyl-N- propyhaminocarbonylmethvlVpyrrolidine-3-carboxylic acid The title compound was prepared by the procedures described in Examples 1 and 49 substituting 3,4-dimethoxybenzaldehyde for piperonal in Example 49A. Rotational isomers are seen in the NMR. 1 H NMR (300 MHz, CDCI3) δ 7.33 (2H, d, J=7.5 Hz), 7.07 (1H, d, J=2.0 Hz), 6.98 (1 H, m), 6.85 (1 H, d, 7.5 Hz), 6.82 (2H, d, 7.5 Hz), 3.91 (3H, s), 3.86 (3H, s), 3.83 (1 H, m), 3.79 (3H, s), 3.64 (1 H, m), 3.50-2.95 (6H, m), 2.87 (1 H, m), 2.85, 2.83 (3H, s), 1.45 (2H, m), 0.84, 0.74 (3H, t, J=7.5 Hz). MS (DCI/NH3) m/e 471 (M+H) + . Anal calc for C26H34N2O6 ■ 0.5 H 2 0: C, 65.12; H, 7.36; N, 5.84. Found: C, 65.22; H, 7.27; N, 5.59. Example 55 frans.frans-2-f4-Methoxyphenvπ-4-ι / 3-methoχyphenvπ-1-fN-methyl-N- proovham inocarbonylmethyl Vpyrrolidine-3-carboxylic acid The title compound was prepared by the procedures described in Examples 1 and 49 substituting 3-methoxybenzaldehyde for piperonal in Example 49A. Rotational isomers are seen in the NMR. 1 H NMR (300 MHz, CDCI 3 ) δ 7.33 (2H, d, J=7.5 Hz), 7.24 (1 H, t, J=7.5 Hz), 7.05 (2H, m), 6.85 (2H, dd, J=7.5&2 Hz), 6.76 (1 H, m), 3.83 (1H, m), 3.81 (3H, s), 3.79 (3H, s), 3.64 (1 H, m), 3.48-2.97 (6H, m), 2.87, 2.83 (3H, s), 2.85 (1 H, m), 1.45 (2H, m), 0.84, 0.74 (3H, t, J=7.5 Hz). MS (DCI/NH3) m/e 441 (M+H) + . Anal calc for C25H32N2O5 • 0.5 H 2 0: C, 66.80; H, 7.40; N, 6.23. Found: C, 66.76; H, 7.36; N, 6.05. Example 56 frans. frans-2-(4-Methoxvphenvn-4-f2-naphthvn-1-(N-methyl-N- propvnaminocarbonvlmethvn-pvrrolidine-3-carboxvlic acid The title compound was prepared by the procedures described in Examples 1 and 49 substituting naphthylene-2-carboxaldehyde for piperonal in Example 49A. Rotational isomers are seen in the NMR. 1 H NMR (300 MHz, CDCI3) δ 7.82 (4H, m), 7.69 (1H, m), 7.47 (2H, m), 7.37 (2H, dd, J=7.5&2 Hz), 6.85 (2H, dd, J=7.5&2 Hz), 3.90 (1H, d, J=8 Hz), 3.78 (3H, s), 3.57 (1H, m), 3.52-2.97 (6H, m), 2.93, 2.85 (3H, s), 2.90 (1 H, m), 1.52 (2H, m), 0.86, 0.76 (3H, t, J=7.5 Hz). MS (DCI/NH 3 ) m/e 461 (M+H) + . Anal calc for C28H32N2O4 • 0.5 H 2 0: C, 71.62; H, 7.08; N, 5.97. Found: C, 71.58; H, 7.11 ; N, 6.01. Example 57 frans.frans-2-(4-Methoxyphenvn-4-(1.3-benzodioxol-5-vn-1-f2-ι , ethvlsulfinvnethyn- pvrrolidine-3-carboxvlic acid To the compound resulting from Example 1C (100 mg, 0.27 mmol) and 2-chloroethyl ethyl sulfide (67.5 mg, 0.5 mmol, 2 equivalents) dissolved in 6 mL of acetonitrile was added 10 mg of Kl and 0.5 mL of diisopropylethylamine. The mixture was refluxed for 4 hours and then concentrated in vacuo. The residue obtained was purified by flash chromatography on silica gel eluting with 4:1 hexane-ethyl acetate to afford 93 mg (75%) of the ethylthioethyl compound. To the sulfide (90 mg, 0.2 mmol) dissolved in 5 mL of CH2CI2 in an ice bath was added 68 mg of 3-chloroperoxybenzoic acid. The mixture was stirred for 40 minutes in the ice bath and for 3 hours at room temperature. A 10% solution of sodium hydroxide (2 mL) was added, and the mixture was extracted with EtOAc (2 x 50 mL). The combined organic extracts were washed with water and brine, dried over sodium sulfate and concentrated in vacuo. The residue obtained was chromatographed on silica gel eluting with EtOAc and 10% MeOH in CH2CJ2 to afford the sulfoxide (62 mg, 65%). The ethyl ester was hydrolyzed by the procedure described in Example 1D to afford the title compound as a diastereomeric mixture, m.p. 61-63 °C. MS (DCI/NH 3 ) m/e 446 (M+H) + . 1 H NMR (CDCI3, 300 MHz) δ 1.25, 1.32 (t, J=9Hz, 3H), 2.45-2.75 (m, 4H), 2.84-2.96 (m, 3H), 3.02- 3.08 (m, 1 H), 3.32, 3.36 (d, J=3Hz, 1 H), 3.47-3.58 (m, 2H), 3.65, 3.68 (d, J=7.5Hz, 1 H), 3.76, 3.80 (s, 3H), 5.94 (s, 2H), 6.72 (d, J=7.5Hz, 1 H), 3.84- 3.89 (m, 3H), 7.02 (d, J=6Hz, 1 H), 7.30, 7.34 (d, J=7.5Hz, 2H). Example 58 frans. frans-2-(4-Methoxvphenvn-4-M .3-benzodioxol-5-vn-1-r2- (isopropylsulfonvlamino^ethvn-Pvrrolidine-3-carboxylic acid To 2-bromoethylamine hydrobromide (1 mmol) suspended in anhydrous CH3CN was added 1 equivalent of Et3N. The mixture was stirred for 30 minutes and then 1 equivalent of isopropyl sulfonyl chloride and 1 equivalent of ET.3N were added. The resulting mixture was stirred for 2 hours at room temperature and then added to a solution of the compound resulting from Example 1 C (185 mg, 0.5 mmol) in 3 mL of CH3CN. The mixture was warmed at 50-60 °C for 2 hours, cooled to room temperature, treated with water and extracted with EtOAc. The combined organic extracts were washed with water and brine, dried and concentrated in vacuo. The residue obtained was chromatographed on silica gel eluting with 3:2 hexane-EtOAc to give 195 mg (75%) of the ethyl ester. The ethyl ester (160 mg, 0.31 mmol) was hydrolyzed by the procedure described in Example 1 D to afford the title compound (133 mg, 88%). m.p. 94-96 °C. 1 H NMR (CD3OD, 300 MHz) δ 1.26 (d, J=6Hz, 6H), 1.97 (s, 1 H), 2.38 (m, 1 H), 2.77 (m, 1 H), 2.88 (t, J=9Hz, 1H), 3.04 (m, 1 H), 3.14 (t, J=7.5Hz, 2H), 3.35 (m, 2H), 3.46 (m, 1 H), 3.58 (m, 1 H), 3.78 (s, 3H), 5.92 (s, 2H), 6.74 (d, J=9Hz, 1 H), 6.86 (dd, J=9Hz,3Hz, 1 H), 6.92 (d, J=9Hz, 2H), 7.00 (d, J=3Hz, 1 H), 7.36 (d, J=9Hz, 2H). MS (DCI/NH3) m/e (M+H) + . Example 59 frans.frans-2-f4-Methoxvρhenvn-4-n .3-benzodioxol-5-yn-1-f2-πsobutoxy^ethvn- Pyrrolidine-3-carboxylic acid The title compound was prepared by the procedures described in Example 1D from the compound resulting from Example 1C and 2- (isobutoxy)ethyl bromide, m.p. 68-70 °C. 1 H NMR (CDCI3. 300 MHz) δ 0.88 (d, J=6Hz, 6H), 1.82 (quintet, J=6Hz, 1 H), 2.22 (m, 2H), 2.72-2.79 (m, 1 H), 2.86-2.95 (m, 2H), 3.13 (d, J=6Hz, 2H), 3.45-3.56 (m, 4H), 3.68 (d, J=9Hz, 1 H), 3.79 (s, 3H), 5.94 (s, 2H), 6.72 (d, J=7.5Hz, 1 H), 6.85 (dd, J=9Hz, 7.5 Hz, 3H), 7.08 (s, 1H), 7.34 (d, J=9Hz, 2H). MS (DCI/NH3) m/e 442 (M+H) + . Example 60 frans. frans-2- 4-Methoxyphenvh-4-f1.3-benzodioxol-5-vn-1-fbutylsulfonyn- pyrrolidine-3-carboxylic acid To 100 mg (0.271 mmol) of the compound resulting from Example 1C dissolved in 10 mL of THF was added 1-butanesulfonyl chloride (46.7 mg, 1.1 equivalents) and diisopropylethylamine (53 mg, 1.5 equivalents). The resulting mixture was stirred for 2.5 hours at room temperature and then the solvent evaporated. The crude product was purified by flash chromatography on silica gel eluting with 3:2 hexane-EtOAc to afford 120 mg (90%) of the ethyl ester. The ester (120 mg, 0.244 mmol) was dissolved in 1 mL of EtOH, and a solution of 100 mg of NaOH in 1 mL of water was added. The mixture was stirred for 3 hours at room temperature and then concentrated under reduced pressure. Water (5 mL) was added and the solution was washed with ether to remove any unhydrolyzed trans-cis isomer. The aqueous solution was acidified to pH-6 with acetic acid and then extracted with EtOAc (2 x 50 mL). The combined organic extracts were washed with brine, dried over sodium sulfate and concentrated under reduced pressure to afford the pure title compound (60 mg, 53%) as a white solid, m.p. 67-69 °C. 1 H NMR (CDCI3, 300 MHz) δ 0.82 (t, J=7.5Hz, 3H), 1.20-1.33 (m, 2H), 1.58-1.68 (m, 2H), 2.48-2.69 (m, 2H), 3.28 (dd, J=9Hz, 1H), 3.49 (t, J=12Hz, 1H), 3.65 (dd, J=12Hz, 1 H), 3.82 (s, 3H), 4.32 (dd, J=12Hz, 1H), 5.17 (d, J=9Hz, 2H), 5.95 (s, 2H), 6.70-6.78 (m, 3H), 6.92 (d, J=9Hz, 2H), 7.35 (d, J=9Hz, 2H). MS (DCI/NH 3 ) m/e 462 (M+H) + . Example 61 frans.frans-2-f4-Methoxyphenvn-4-(1.3-benzodioxol-5-vn-1-(2-(N-methyl-N- isopropylcarbonylamino^ethvn-Pyrrolidine-3-carboxylic acid Example 61A frans.frans-2-(4-Methoxyphenyn-4-(1.3-benzodioxol-5-yl)-1-f2-bromoethyl)- pyrroIidine-3-carboxylic acid ethyl ester To the mixture of cis.trans and trans.trans pyrrolidines resulting from Example 1C (400 mg) dissolved in 9 mL of 1 ,2-dibromoethane was added 0.7 mL of diisopropylethylamine and 30 mg of sodium iodide. The resultant mixture was heated at 100 °C for 1 hour, and then the solvents were removed in vacuo. The residue was taken up in EtOAc and washed sequentially with water and brine, dried and concentrated under reduced pressure. The crude product was purified by flash chromatography on silica gel eluting with 4:1 hexane-EtOAc to give 470 mg of the title product. Example 61 B frans.frans-2-(4-Methoxyphenvn-4-(1.3-benzodioxol-5-yn-1-f2-(methylamino^ethyπ- pyrrolidine-3-carboxvlic acid ethyl ester To the compound resulting from Example 61 A (450 mg) dissolved in 10 L of EtOH was added 0.5 mL of 40% aqueous methylamine and 50 mg of sodium iodide. The mixture was heated at 80 °C for 1 hour, and then the solvents were removed in vacuo. The residue was taken up in EtOAc and washed sequentially with water and brine, dried and concentrated in vacuo. The resultant product was carried on without further purification. Example 61 C frans.frans^-M-Methoxyphenyh^-π ^-benzodioxol-S-yn-l-^-fN-methyl-N- isobutvrvlamino)ethvn-pvrrolidine-3-carboxylic acid To the compound resulting from Example 61 B (-150 mg) dissolved in 5 mL of 1 ,2-dichloroethane was added 0.3 mL of diisopropylethylamine. The solution was cooled to -40 °C, isobutyryl chloride (0.17 mL) was added, the bath was removed, and the solution was allowed to warm to ambient temperature and stirred for 15 hours. The solvent was removed in vacuo; the residue was taken up in EtOAc and washed sequentially with 1 :1 sodium bicarbonate solution/water and brine, dried and concentrated in vacuo. The product was purified by flash chromatography on silica gel eluting with a gradient 1 :1 EtOAc- hexanes going to EtOAc and finally using 10% MeOH-EtOAc. The ester was dissolved in 1.5 mL of EtOH; 0.75 mL of a 17% aqueous NaOH solution was added, and the resultant mixture was stirred at ambient temperature for 3 hours. The solvents were removed in vacuo; the residue was taken up in water and washed with ether. The aqueous phase was acidified with 1 J H3PO4 to pH 3 and extracted twice with ether. The combined organic extracts were washed with brine and dried over Na2Sθ4. The solvents were removed in vacuo to provide 82 mg of the title compound as a white foam. Rotamers were seen in the NMR. 1 H NMR (CDCI3. 300 MHz) of the major rotamer δ 1.06 (d, 3H, J=10Hz), 1.12 (d, 3H, J=10Hz), 2.15 (m, 1H), 2.5-3.0 (m, 3H), 2.91 (s. 3H), 3.32 (m, 2H), 3.50 (m, 2H), 3.65 (m, 2H), 3.77 (s, 3H), 5.92 (s, 2H), 6.73 (d, 1H, J=8Hz), 6.75-6.9 (m, 4H), 6.96 (d, 1H, J=2Hz), 7.29 (m, 1H). MS (DCI/NH3) m/z 469 (M+H)+. Analysis calcd for C26H 3 2N2O 6 • 0.3 TFA: C, 63.55; H, 6.48; N, 5.57. Found: C, 63.44; H, 6.71 ; N, 5.24. Example 62 frans. frans-2-t4-Methoxvphenvn-4-n.3-benzodioxol-5-vh-1-f2-fN-methyl-N- propionvlaminotethvn-pvrrolidine-3-carboxvlic acid The title compound was prepared by the procedures described in Example 61 substituting propionyl chloride for isobutyryl chloride in Example 61 C. 1 H NMR (CDCI3, 300 MHz) of the major rotamer δ 1.13 (t, 3H, J=8Hz), 2.19 (m. 1H), 2.30 (m, 2H), 2.65-3.0 (m, 3H), 2.85 (s, 3H), 3.25-3.4 (m, 2H), 3.5-3.7 (m, 3H), 3.79 (s, 3H), 5.92 (s, 2H), 6.74 (d, 1H, J=8Hz), 6.75-6.9 (m, 4H), 7.00 (bd s, 1H), 7.29 (bd s, 1H). MS (DCI/NH3) m/z 455 (M+H)+. Analysis calcd for C25H30N2O6 • 1.0 H 2 0: C, 63.55; H, 6.83; N, 5.93 . Found: C, 63.55; H, 6.52; N, 5.73. Example 63 frans.frans-2-f4-Methoxyphenvn-4-(1.3-benzodioxol-5-vn-1-(N-methyl-N- benzylaminocarbonylmethvD-Pyrrolidine-3-carboxylic acid Using the procedures described in Example 1 the title compound was prepared. 1 H NMR (CDCI3, 300 MHz) of the major rotamer δ 2.79 (s, 3H), 2.8-3.2 (m, 2H), 3.48 (m, 2H), 3.61 (m, 2H), 3.77 (s, 3H), 3.78 (m, 1 H), 4.3-4.5 (m, 2H), 5.95 (d, 2H, J=2Hz), 6.7-6.9 (m, 4H), 7.00 (m, 1H), 7.15-7.35 (m, 7H). MS (FAB/NBA) m/z 503 (M+H)+. Anal calcd for C2 9 H 30 N2O 6 • 0.5 H 2 0: C, 68.36; H.5.74; N, 5.50. Found: C.68.41; H, 5.74; N, 5.36 . Example 64 frans.frans-2-f4-Methoxvphenvn-4-f1.3-benzodioxol-5-yl)-1-(N-ethyl-N- butvlaminocarbonvlmethvn-Pvrrolidine-3-carboxvlic acid Using the procedures described in Example 1 the title compound was prepared. 1 H NMR (CDCI3, 300 MHz) of the major rotamer δ 0.88 (t, 3H, J=7Hz), 1.06 (t, 3H, J=7Hz), 1.27 (m, 2H), 1.45 (m, 2H), 2.8-3.6 (m, 11 H), 3.79 (s,3H), 3.80 (m, 1 H), 5.92 (bd s, 2H), 6.75 (d, 1 H, J=8Hz), 6.85 (d, 1H, J=8Hz), 6.92 (d, 2H, J=8Hz), 7.03 (s, 1H), 7.33 (d, 1 H, J=8Hz). MS (DCI/NH3) m/z 483 (M+H) + . Anal calcd for C27H34N2O6 • 0.5 HOAc: C, 65.61 ; H.7.08; N, 5.46. Found: C.65.51 ; H, 6.70; N, 5.66. Example 65 frans.frans-2-M-Methoxvphenvl)-4-f1.3-benzodioxol-5-vn-1 -fN-methvl-N-r2.2- dimethylpropyl)aminocarbonylmethylVpyrrolidine-3-carboxylic acid Using the procedures described in Example 1 the title compound was prepared. 1 H NMR (CDCI3. 300 MHz) of the major rotamer δ 0.90 (s, 9H), 2.8-3.1 (m, 4H), 2.94 (s, 3H), 3.3-3.5 (m, 3H), 3.61 (m, 1 H), 3.80 (s, 3H), 3.82 (m, 1H), 5.94 (bd s, 2H), 6.74 (d, 1 H, J=8Hz), 6.86 (d, 2H, J=8Hz), 6.87 (m, 1 H), 7.03 (d, 1H, J=2Hz), 7.33 (d, 2H, J=8Hz). MS (DCI/NH3) m/z 483 (M+H)+. Example 66 frans.frans-2-(4-Methoxyphenvh-4-M .3-benzodioxol-5-vh-1-f2-fN-methyl-N- butylsulfonylamino ethvπ-Pyrrolidine-3-carboxylic acid To the compound resulting from Example 61 B (60 mg, 0.13 mmol) dissolved in 5 mL of CH3CN was added 0.2 mL of Et3N and 22 mg (0.143 mmol, 1.1 equivalents) of 1 -butanesulfonyl chloride. The mixture was stirred for 1 hour at room temperature and then concentrated in vacuo. The crude product was purified by column chromatography on silica gel eluting with 1 :1 EtOAc-hexane to yield 64 mg (90%) of the ester. Ester hydrolysis by the procedure described in Example 1 D afforded the title compound, m.p. 64-66 °C. 1 H NMR (CDCI3, 300 MHz) δ 0.92 (t, J=7.5Hz, 3H), 1.39 (hexad, J=7.5Hz, 2H), 1.68-1.76 (m, 2H), 2.16-2.25 (m, 1H), 2.72 (s, 3H), 2.75-2.92 (m, 5H), 3.12-3.20 (m, 1 H), 3.25-3.34 (m, 1 H), 3.46-3.55 (m, 2H), 3.65 (d, J=9Hz, 1 H), 3.78 (s, 3H), 5.53 (s, 2H), 6.72 (d, J=7.5Hz, 1H), 6.82 (dd, J=7.5Hz,3Hz, 1H), 6.86 (d, J=9Hz, 2H), 7.02 (d, J=3Hz, 1 H), 7.34 (d, J=9Hz, 2H). MS (DCI/NH3) m/e 519 (M+H) + . Example 67 trans. frans-2-(4-MethoxvphenvlV4-M .3-benzodioxol-5-vn-1-(2-(N-methyl-N- propvlsulfonvlaminotethvn-pvrrolidine-3-carboxylic acid The title compound was prepared by the procedures described in Example 66 substituting 1-propanesulfonyl chloride for 1- butanesulfonyl chloride, m.p. 69-70 °C. 1 H NMR (CDCI 3 , 300 MHz) δ 1.02 (t, J=7.5Hz, 3H), 1.78 (hexad, J=7.5Hz, 2H), 2.18-2.26 (m, 1H), 2.72 (s, 3H), 2.75-2.95 (m, 6H), 3.13-3.22 (m, 1 H), 3.25-3.35 (m, 1 H), 3.47-3.58 (m, 2H), 3.66 (d, J=9Hz, 1H), 3.80 (s, 3H), 5.96 (s, 2H), 6.74 (d, J=7.5Hz, 1H), 6.84 (d,d, J=7.5Hz, 3Hz, 1 H), 6.87 (d, J=9Hz, 2H), 7.04 (d, J=3Hz, 1H), 7.43 (d, J=9Hz, 2H). MS (DCI/NH3) m/e 505 (M+H) + . Example 68 frans. frans-2- -Methoxyphenvπ-4-(1.3-benzodioxol-5-vh-1 -(2- (propylsulfonvnethvn-pyrrolidine-3-carboxylic acid To 1-propanethiol (3.5 g, 46.05 mmol) dissolved in 10 mL of anhydrous THF was added 632 mg (26.32 mmol) of NaH in portions under a nitrogen atmosphere. The mixture was heated at 60-70 °C for 1 hours. To this mixture was added the compound resulting from Example 61 A (180 mg, 0.38 mmol) in 2 mL THF. Heating was continued at 60-70 °C for an additional 2 hours, and then the volatiles were removed under reduced pressure. The crude propylthioethyl adduct was purified by flash chromatography on silica gel eluting with 3:2 hexane- EtOAc to give 170 mg (95%). To a solution of 170 mg (0.36 mmol) of the sulfide and 93 mg (0.8 mmol) of N-methylmorpholine N-oxide (NMO) in a mixture of 20 mL of acetone and 5 mL of H2O was added a solution of osmium tetroxide (10 mg) in 0.3 mL of t-butanol. The resulting mixture was stirred overnight at room temperature and then concentrated under reduced pressure. The residue was partitioned between EtOAc and H2O. The organic phase was washed with brine, dried over Na2Sθ4 and concentrated in vacuo. Flash chromatography afforded 177 mg (98%) of the ethyl ester which was hydrolyzed by the procedures described in Example 1D to afford the title compound, m.p. 73-75 °C. 1 H NMR (CDCI3, 300 MHz) δ 1.04 (t, J=7.5Hz, 3H), 1.78 (hexad, J=7.5Hz, 2H), 2.59-2.66 (m, 1 H), 2.84-3.08 (m, 7H), 3.43 (dd, J=9Hz, 3Hz, 1H), 3.53-3.60 (m, 1 H), 3.68 (d, J=9Hz, 1 H), 3.82 (s, 3H), 5.96 (s, 2H), 6.75 (d, J=7.5Hz, 1H), 6.82 (dd, J=7.5Hz, 3Hz, 1H), 6.88 (d, J=9Hz, 2H), 6.99 (d, J=3Hz, 1H), 7.32 (d, J=9Hz, 2H). MS (DCI/NH 3 ) m/e 476 (M+H) + . Example 69 frans.frans-2-(4-Methoxvphenvn-4-π .3-benzodioxol-5-vn-1-N-rfrans-5-methylhex- 2-enylVpyrrolidine-3-carboxylic acid Example 69A frans-5-Methvlhex-2-enoic acid ethvl ester Oil dispersion sodium hydride (0.85 g) was washed with hexanes and suspended in THF (20 mL), and the mixture was cooled in an ice bath to 0 °C. Diisopropyl(ethoxycarbonylmethyl) phosphonate (5.0 mL) was added slowly and the mixture stirred for 20 minutes at 0 °C. Isovaleraldehyde (2.0 mL) in THF (5 mL) was added dropwise over five minutes. The ice bath was removed and the mixture stirred for 18 hours at ambient temperature. Saturated ammonium chloride solution (50 mL) was added and the mixture extracted with diethyl ether (3 x 50 mL). The ether extracts were combined, dried with Na2Sθ 4 , and evaporated to give a colorless oil which was purified by flash chromatography on silica gel eluting with hexanes. The title compound was isolated as a colorless oil (2.1 g). Example 69B trans- 5-Methylhex-2-en-1 -ol The compound resulting from Example 69A (2.0 g) was dissolved in toluene and cooled to 0 °C in an ice bath. Diisobutylaluminum hydride (1.5 ϋ in toluene, 20 mL) was added dropwise and the solution stirred at 0 °C for two hours. Citric acid solution (25 mL) was added very slowly to the cooled solution. The resulting mixture was stirred for 18 hours at ambient temperature. Diethyl ether (50 mL) was added, the solids removed by filtration and washed with additional ether (2 x 25 mL). The filtrate was extracted with ether (2 x 25 mL). The ether extractions and washings were combined, dried, and evaported to give a colorless oil which was purified by flash chromatography on silica gel eluting with 25% EtOAc-hexanes. The title compound was isolated as a colorless oil (1.25 g). Example 69C 5 trans- 1 -Bromo-5-methvlhex-2-ene The compound resulting from Example 69B (1.0 g) was dissolved in diethyl ether and cooled to 0 °C in an ice bath. Phosphorus tribromide (2.5 g, 0.87 mL) was added dropwise and the solution stirred at 0 °C for two hours. The solution was poured onto ice, the layers separated, and ι o the aqueous layer extracted with additional ether (3 x 25 mL). The ether layers were combined, dried, and evaporated to give a colorless oil which was used without further purification (0.95 g). Example 69P 15 frans. frans-2- 4-Methoχyphenvn-4-f1.3-benzodioxol-5-vn-1-N-ιfrans-5-methylhex- 2-envn-pyrrolidine-3-carboxylic acid The title compound was synthesized using the methods detailed in Example 1 D but substituting the compound resulting from Example 69C for N-propyl bromoacetamide. 1 H NMR (CDCI3. 300 MHz) δ 0.84 (d, 6H, 20 J=8Hz), 1.57 (heptet, 1 H, J=8Hz), 1.87 (t, 2H, J=6Hz), 2.60 (dd, 1 H, J=8Hz,14Hz), 2.86 (t, 1 H, J=10Hz), 2.96 (dd, 1 H, J=8Hz,10Hz), 3.20 (dd, 1 H, J= 5Hz,14Hz), 3.29 (dd, 1 H, J=3Hz,10Hz), 3.50 (m, 1H), 3.70 (d, 1 H, J=10Hz), 3.78 (s, 3H), 5.47 (m, 2H), 5.93 (s, 2H), 6.71 (d, 1 H, J=8Hz), 6.83 (d, 3H, J=9Hz), 7.05 (s, 1 H), 7.32 (d, 2H, J=9Hz). MS (DCI/NH3) m/e 25 438 (M+H)+. Anal calcd for C26H31NO5: C, 71.37; H, 7.14; N, 3.20. Found: C, 71.16; H, 7.24; N, 3.17. Example 70 frans.frans-2-r4-Methoxyphenvn-4-n .3-benzodioxol-5-vlV1-N-(frans-3.5- 30 dimethylhex-2-envh-pvrrolidine-3-carboxvlic acid The title compound was prepared by the procedures described in Example 69 but substituting 4-methyl-2-pentanone for isovaleraldehyde in Example 69A, which gave -7:1 mixture of trans/cis olefins. The crude product was purified by preparative HPLC (Vydac 35 μC18) eluting with a 10-70% gradient of CH3CN in 0.1% TFA. The desired fractions were lyophilized to give the product (and its diastereomer) as a white solid. 1 H NMR of the major (trans) isomer: (CDCI 3 , 300 MHz) δ 0.83 (d, 6H, J=8Hz), 1.56 (s,3H), 1.74 (m, 1H), 1.92 (d, 2H, J=6Hz), 3.3-3.5 (m, 3H), 3.6-3.8 (m,4H), 3.78 (s, 3H), 3.9-4.0 (m, 1 H), 5.22 (m, 1H), 5.90 (d, 2H, J=12Hz), 6.63 (m, 1H), 6.78 (m, 3H), 6.95 (s, 1H), 7.45 (d, 3H, J=8Hz). MS (DCI/NH3) m/e 438 (M+H)+. Anal calcd for C27H3 3 NO5 • 1.0 TFA: C, 61.59; H, 6.06; N, 2.48. Found: C, 61.36; H, 6.10; N, 2.34. Example 71 frans. frans-2-f4-Methoxvphenvn-4-π.3-benzodioxol-5-vn-1- - heptylcarbonylmethyπ-pyrrolidine-3-carboxylic acid Example 71 A 1 -Chloro-3-propyl-2-hexanone To 2-propylpentanoic acid (156.6 μl, 1.00 mmol) dissolved in anhydrous dichloromethane (2 mL) was added DMF (3 μL, 4 mole %), and the solution was cooled to 0 °C under a nitrogen atmosphere. To the solution was added oxalyl chloride (94.3 μL, 1.08 mmol) dropwise over a few minutes. The reaction was stirred 18 hours while warming to ambient temperature. The mixture was cooled to 0 °C and excess -0.3 M. ethereal diazomethane solution was added. The reaction mixture was stirred 18 hours while warming to ambient temperature. The reaction mixture was washed with 1 M. aqueous sodium carbonate solution (30 mL), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was dissolved in ether (2 mL) and cooled to 0 °C under a nitrogen atmosphere. Hydrogen chloride as a 4 N . solution in dioxane (275 μL, 1.10 mmol) was added dropwise over a few minutes. The reaction was stirred 18 hours while warming to ambient temperature. The reaction mixture was concentrated under reduced pressure and the residual oil was used in the next step without further purification. Example 71 B trans .trans- Ethyl 2-(4-methoxyphenvh-4-( 1 ,3-benzodioxol-5-yh-1 - M-heptylcarbonylmethvπ-pyrrolidine-3-carboxylate To the compound resulting from Example 71 A (1.00 mmol, maximum theoretical yield) was added a solution of the trans.trans ethyl carboxylate from Example 1C (295 mg, 0.80 mmol as a 50 % solution in toluene), diisopropylethylamine (700 μL, 4.00 mmol) and acetonitrile (4 mL). To the resulting solution was added sodium iodide (12 mg, 10 mole %), and the reaction mixture was stirred 18 hours under a nitrogen atmosphere at ambient temperature. Additional 5 sodium iodide (24 mg, 20 mole %) and acetonitrile (4 mL) were added, and the reaction mixture was heated at 45-50 °C with stirring for 18 hours. The reaction mixture was concentrated under reduced pressure, and the residue was chromatographed on silica gel eluting with 1 :9 ethyl acetate-hexane to give 237 mg (46%) of the title compound as a ι o yellow oil. Example 71 C frans.frans-2-ι / 4-MethoxvPhenvh-4-n .3-benzodioxol-5-vn-1 -U- heptylcarbonylmethvh-pyrrolidine-3-carboxylic acid 15 To the compound resulting from Example 71 B (231 mg, 0.4532 mmol) dissolved in ethanol (10 mL) was added a solution of lithium hydroxide (38 mg, 0.9065 mmol) in water (2.5 mL). The solution was stirred for 18 hours under a nitrogen atmosphere, additional lithium hydroxide (19 mg, 0.4532 mmol) in water (0.5 mL) was added, and 20 stirring was continued 24 hours. The reaction mixture was concentrated under reduced pressure to remove the ethanol, and the aqueous residue was diluted with water (45 mL) and washed with ether (50 mL). The aqueous layer was neutralized with 1 N. hydrochloric acid to cloudiness and then 10% aqueous citric acid was added to adjust the 25 pH to -5. This solution was then extracted with 10% ethanol in chloroform (4 x 25 mL). The combined organic extracts were dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by preparative TLC on silica gel eluted with 1 :1 ethyl acetate-hexane to give 86 mg (39%) of the title 30 compound as an off white powder. 1 H NMR (CDCI3, 300 MHz) δ 0.73-0.97 (m, 6H), 1.03-1.33 (m, 6H), 1.36-1.58 (m, 2H), 2.46 (m, 1H), 2.80-2.98 (m, 3H), 3.38-3.64 (m, 3H), 3.75-3.90 (m, 1H), 3.79 (s, 3H), 5.94 (s, 2H), 6.75 (d, 1 H), 6.86 (d, 2H), 6.92 (d, 1H), 7.12 (s, 1 H), 7.32 (d, 2H). MS (FAB) m/e 482 (M+H)+. Anal calcd for C28H35NO6: C, 69.83; H, 7.32; N, 35 2.91. Found: C, 69.57; H, 7.41 ; N, 2.73. Example 72 frans. frans-2-(4-Methoxyphenyn-4-π.3-benzodioxol-5-vn-1-(valerylmethyn- pyrrolidine-3-carboxylic acid Example 72A 1 -Chloro-2-hexanone Using the procedure described in Example 71 A and substituting pentanoic acid for 2-propylpentanoic acid afforded the title compound as an oil which was used in the next step without further purification. Example 72P trans. frans-Ethyl 2-(4-methoxyphenyh-4-M .3-benzodioxole-5-yπ-1 fvalerylmethvh-pyrrolidine-3-carboxylate Substituting the compound resulting from Example 72A for 1- chloro-3-propyl-2-hexanone and using the procedure described in Example 71 B, except deleting the first addition of sodium iodide, stirring 18 hours at ambient temperature and purifying by silica gel chromatography eluting with 3:17 ethyl acetate-hexane, the title compound 305 mg (65%) was obtained as a yellow oil. Example 72C frans. frans-2-,4-Methoxyphenyn-4-M .3-benzodioxol-5-yn-1 - (valerylmethyh-pyrrolidine-3-carboxylic acid By substituting the compound resulting from Example 72B for trans, trans- Ethyl 2-(4-methoxyphenyl)-4-(1 ,3-benzodioxol-5-yl)-1 - (4-heptylcarbonylmethyl)-pyrrolidine-3-carboxylate and using the procedure described in Example 71 C, except only one solution of lithium hydroxide (81.5 mg, 1.942 mmol) in water (3.5 mL) was added followed by stirring for 18 hours, the title compound 130 mg (46%) was obtained as an off white powder. 1H NMR (CDCI 3 , 300 MHz) δ 0.87 (t, 3H), 1.26 (m, 2H), 1.49 (m, 2H), 2.37 (m, 2H), 2.79-2.98 (m, 3H), 3.31- 3.49 (m, 2H), 3.56 (m, 1 H), 3.77, 3.79 (d,s, 4H), 5.94 (s, 2H), 6.75 (d, 1H), 6.81-6.93 (m, 3H), 7.09 (d, 1 H), 7.33 (d, 2H). MS (FAB) m/e 440 (M+H) + . Anal, calcd for C25H29NO6: C, 68.32; H, 6.65; N, 3.19. Found: C, 67.95; H, 6.64; N, 3.05. Examp g 73 frans.frans-2-ι , 4-Methoxvphenvn-4-n.3-benzodioxol-5-vn-1- / N-^3.4- dimethoxybenzvπ-N-methylaminocarbonylmethvπpyrrolidine-3-carboxylic acid Example 73A trans.trans- and cis.trans-2-(4-Me\hoxyD eny\)-4-( ι .3-benzodioxol-5- yn-1 -ff3.4-dimethoxybenzynaminocarbonylmethynDyrrolidine-3- carboxvlic acid ethyl ester Using the procedure of Example 1 D, paragraph 1 , substituting 3,4- dimethoxybenzyl bromoacetamide for dipropyl bromoacetamide, the desired product mixture was obtained as a white foam in 81% yield. Example 73B trans.trans- and c/s.fraπs-2-(4-Methoxvphenyn-4-(1 .3-benzodioxol-5- yn-1 - N-(3.4-dimethoxvbenzyh-N- methylaminocarbonvlmethynpvrrolidine-3-carboxviic acid ethyl ester The resultant product from Example 73A (220 mg, 0.404 mmol) was dissolved in 2 mL dry THF and added dropwise to a stirred, cooled (0 °C) suspension of sodium hydride (23 mg of a 60% by weight mineral oil suspension, 16.5 mg, 0.69 mmol) in 0.2 mL THF, under an argon atmosphere. The resulting mixture was stirred at 0 °C for 1 hour, then methyl iodide (28 μL, 64 mg, 0.45 mmol) was added. The reaction mixture was stirred at 0 °C for 45 minutes. TLC (Et2θ) indicated incomplete reaction. An additional portion of methyl iodide (28 μL, 64 mg, 0.45 mmol) and dry 1 ,3-dimethyl-3,4,5,6-tetrahydro- 2(1 H)pyrimidinone (50 μL, 0.41 mmol) were added. The reaction mixture was stirred at ambient temperature for 2 days. The reaction was poured into 25 mL of 0.5 M. aqueous citric acid and extracted with 2 x 25 mL EtOAc. The combined organic extrracts were washed sequentially with 30 mL water and 30 mL brine, then dried (Na2Sθ4), filtered and concentrated under reduced pressure to produce 270 mg of crude material. Flash chromatography on silica gel eluting with Et2θ gave the title compounds as an inseparable mixture in 43% yield. 1 H NMR (CDCI3, 300 MHz) δ 2.79 (s) and 2.81 (s), for the N-CH3 signals. MS m/z 591 (M+H) + . Example 73C trans. frans-2- -Methoxyphenyh-4-ι 1 .3-benzodioxol-5-yh-1 -(N-f 3.4- dimethoxybenzvh-N-methylaminocarbonylmethvhpyrrolidine-3- carboxylic acid To the resultant compound from Example 73B (98 mg, 0.17 mmol) dissolved in 1 mL EtOH and cooled to 0 °C was added a solution of lithium hydroxide monohydroxide (17 mg, 0.41 mmol) in 0.5 mL H2O. The resulting solution was stirred under a nitrogen atmosphere for 16 hours. The solution was concentrated in vacuo, and the residue was partitioned between 15 mL H2O and 15 mL Et2θ. The aqueous phase was extracted with 5 mL Et2θ, then the aqueous phase was acidified with 10% aqueous citric acid. The acidic aqueous phase was saturated with NaCI and extracted with 3 x 15 mL EtOAc. The EtOAc extracts were combined, dried (Na2Sθ4), then filtered and concentrated in vacuo to give 40 mg (42%) of the title compound as a white foam. 1 H NMR (CD3OD, 300 MHz, two rotameric forms) δ 2.85 (s, 3H), 2.94-3.25 (br m, 3H), 3.35-3.70 (br m) and 3.64 (s, 4 H total), 3.70-3.97 (br m), 3.74 (s), 3.76 (s), 3.78 (s), 3.79 (s), 3.81 (s), and 4.03 (br d, J=14 Hz, 8H total), 4.43 (AB, 1 H), 5.91 (s) and 5.93 (s, 2H total), 6.50-6.60 (m, 1 H), 6.67- 7.02 (br m, 6H), 7.29 (br d) and 7.35 (br d, 2H total). HRMS calcd for C31H35N2O8 (M+H) + : 563.2393. Found: 563.2385. Example 74 frans.frans-2-(4-Methoxvphenyn-4-f1.3-benzodioxol-5-vn-1-fN-(3.4- dimethoxyben2vπaminocarbonylmethvπpyrrolidine-3-carboxylic acid The procedure of Example 73C was used, with the substitution of the resultant compound from Example 73A for the resultant compound from Example 73B, to provide the title compound. 1 H NMR (CD3OD, 300 MHz) δ 2.85 (d, J=16Hz, 1H), 2.92 (br t, J=9Hz, 1H), 2.98 (br t, J=10Hz, 1 H), 3.32-3.39 (br m, 2H), 3.54-3.65 (br m, 1H), 3.67 (s, 3H), 3.78 (s, 3H), 3.80 (s, 3H), 3.85 (d, J=10 Hz, 1 H), 4.21 (d, J=15Hz, 1H), 4.41 (d, J = 15Hz, 1 H), 5.91 (s, 2H), 6.67 (d, J=8Hz, 1 H), 6.75-6.95 (m, 7H), 7.33-7.40 (m, 2H). HRMS calcd for C30H32 2O8 (M+H) + : 549.2237. Found: 549.2224. Example 75 f2R.3R.4 -2-(4-MethoxyphenylV4-f1.3-benzodioxol-5-yn-1-friR\-1-fN.N- diprppylaminocarbonvn-1-butvl)pyrrolidine-3-carboxylic acid 5 Example 75A fhenzyloxvcarbonvnbutvnpvrrolidine-3-carboxylic acid ethyl ester The procedure of Fung, et. al., J. Med. Chem., 35(10): 1722-34 (1992) was adapted. The resultant compound from Example 6A (103 mg, ι o 0.279 mmol) was dissolved in 0.7 mL of nitromethane and 0.7 mL of H2O, and ammonium carbonate (34 mg, 0.35 mmol) and (2S)-benzyl 2- bromopentanoate (78 mg, 0.30 mmol) were added. The reaction was refluxed for 24 hours. The reaction was partitioned between 15 mL of 1 M aqueous Na2C0 3 and 25 mL of CH2CI2. The aqueous phase was 15 extracted with 2 x 10 mL CH2CI2, and the combined organic phases were washed with 15 mL brine, dried (Na 2 Sθ 4 ), then filtered and concentrated under reduced pressure to a brown oil (169 mg). The crude product was purified by silica gel chromatography eluting with 3:1 CH2Cl2-hexane to produce 106 mg (68%) of the title compound as a 20 waxy solid. 1 H NMR indicated the presence of two diastereomeric products. Example 75B frans.frans-2- -Methoxvphenvn-4-(1.3-benzodioxoI-5-vn-1- iRV1-(N.N- 25 dipropylaminocarbonvn-1-butvnpvrrolidine-3-carboxvlic acid ethyl ester The resultant compound from Example 75A (101 mg, 0.180 mmol) and 30 mg of 10% palladium on charcoal were stirred in 2 mL EtOAc under 1 atmosphere of H2 for 4 hours. The reaction mixture was filtered through a plug of Celite, using 15 mL MeOH to wash the 30 catalyst. The combined filtrate and wash were concentrated in vacuo to give 81.4 mg (96%) of the crude acid as a white solid. The above crude acid was combined with HOBt hydrate (41 mg, 0.27 mmol), dipropylamine (26 mg, 0.26 mmol), and 4-methylmorpholine (37 mg, 0.37 mmol) in 2 mL dry DMF. The solution was cooled to -15 °C, 35 then 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (44 mg, 0.23 mmol) was added. The mixture was stirred at -15 °C and allowed to warm slowly to room temperature overnight. The solvent was removed by distillation under reduced pressure, and the residue was partitioned between 20 mL EtOAc and 10 mL of 1 M aqueous Na2Cθ3- The organic phase was washed with 10 mL of brine, dried (Na2S04), then filtered and concentrated in vacuo. The crude product was purified by flash chromatography on silica gel, eluting with 1 :2 Et2θ-hexane. Further purification of overlap fractions by preparative TLC eluting with 1 :2 Et2θ-hexane yielded 32 mg (34%) of a less polar product, and 44 mg (46%) of a more polar product. Example 75C N.N-dipropylaminocarbonyn-1 -butyπpyrrolidine-3-carboxylic acid The procedure of Example 73C was followed, with the substitution of the less polar isomer from Example 75B for the resultant product from Example 73B, to provide the title compound in 94% yield. [α] D = -52° (c=0.235, CH 3 OH). 1 H NMR (CD3OD, 300 MHz) δ 0.55 (t, J=7Hz, 3H), 0.87 (t, J=7Hz) and 0.87-0.94 (m, 6H total), 1.03- 1.25 (br m, 2H), 1.25-1.68 (br m, 4H), 1.90-2.07 (br m, 1 H), 2.75-2.94 (br m, 2H), 2.94-3.02 (br m, 2H), 3.20-3.40 (m, overlapping with CD HOD signal), 3.40-3.60 (br m, 2H), 3.79 (s, 3H), 4.04 (br d, J=9 Hz, 1H), 5.92 (dd, J=3,5 Hz, 2H), 6.72 (d, J=8 Hz, 1H), 6.79 (dd, J=1.5,8 Hz, 1H), 6.92- 6.98 (br m, 3H), 7.29-7.39 (m, 2H). MS m/z 525 (M+H) + . Example 76 (2S.3S.4S -2-f4-Methoxyphenvn-4-M .3-benzodioxol-5-vh-1 -fri R^-1 - {N.N-dipropylaminocarbonvl -butvl )pvrrolidine-3-carboxylic acid The procedure of Example 73C was followed, with the substitution of the more polar isomer from Example 75B for the resultant product from Example 73B, to provide the title compound in 88% yield. [α]o = +58° (c=0.37, CH3OH). 1 H NMR (CD 3 OD, 300 MHz) δ 0.57 (br t, J=7Hz, 3H), 0.88-0.98 (m, 6H), 1.08-1.35 (br m, 2H), 1.35-1.68 (br m, 4H), 1.75-1.90 (br m, 1H), 2.75-2.86 (br m, 2H), 3.10-3.30 (br m, 2H), 3.51-3.65 (br m, 2 H), 3.69 (s, 3H), 4.03-4.16 (br m, 2H), 5.91 (s, 2H), 6.71-6.83 (m, 2H), 6.86-6.97 (m, 3H), 7.32 (br d, J=9Hz, 2H). MS m/z 525 (M+H) + . Example 77 f2S.3S.4Sι-2-f4-MethoxyDhenylM-M.3-benzodioxol-5-ylι-1-fnSι.1-(N.N. dipropylaminocarbonvn- 1 -butynpvrrolidine-3-carboxylic acid 5 Example 77A frans.frans-2-(4-Methoxvphenvl)-4-M .3-benzodioxol-5-yl^1 -f M Si-1 - fN.N-dipropvlaminocarbonvn-1 -butvnpyrrolidine-3-carboxylic acid ethyl ester (2R)-N,N-dipropyl 2-hydroxypentanamide (106 mg, 0.528 mmol, o made by standard procedure) was dissolved in 2 mL THF under an argon atmosphere, diisopropylethylamine (75 mg, 0.58 mmol) was added, then the solution was cooled to -20 °C. Trifluoromethanesulfonic anhydride (95 μL, 159 mg, 0.565 mmol) was added to the cooled solution over 1 minute, and the reaction mixture was stirred at -20 °C for 1 hour, and 5 at room temperature for an additional 1 hour. The resulting slurry was recooled to 0 °C, and a solution of the resultant compound from Example 6A (195 mg, 0.528 mmol) and diisopropylethylamine (101 μL, 75 mg, 0.58 mmol) in 3 mL of CH2CI2 was added. The reaction was stirred at 0 °C for 3 hours and for an additional 2 days at room temperature. TLC 0 (Et2θ-hexane 1:2) indicated starting materials remained, so the mixture was warmed to reflux for 4 hours. The reaction was cooled, then partitioned between 30 mL EtOAc and 15 mL of 1 aqueous Na2Cθ3. The aqueous phase was extracted with 15 mL EtOAc, then the combined organic phases were washed with 20 mL brine, dried (Na2S04), filtered 5 and concentrated in vacuo to a yellowish oil. Purification by flash chromatography on silica gel eluting with 1:2 Et2θ-hexane gave 19.9 mg (7%) of a less polar product and 20.1 mg (7%) of a more polar product. 1 H NMR spectra and MS were the same as those of Example 76B. 0 Example 77B 2S.3S.4SV2-f4-Methoxyphenvn-4.M.3-benzodioxol-5-vlV1-fnS l-fN N- dipropylaminocarbonyl -butyl rrolidine-3-carboxvlic acid The procedure of Example 73C was followed, with the substitution of the less polar isomer from Example 77A for the 5 resultant product from Example 73B, to provide the title compound in 100% yield. 1 H NMR (CD3OD, 300 MHz) and MS identical to those of Example 75C. Example 78 f2R.3R.4RV2-ι , 4-Methoxyphenyn-4-π .3-benzodioxol-5-vh-1- ( M SV1-fN.N- dipropylaminocarbonvn- 1 -butvnpvrrolidine-3-carboxylic acid The procedure of Example 73C was followed, with the substitution of the more polar isomer from Example 77A for the resultant product from Example 73B, to provide the title compound in 88% yield. 1 H NMR (CD 3 OD, 300 MHz) and MS identical to those of Example 76. Example 79 frans.frans-2-ι4-Methoxyphenvπ-4-f1.3-benzodioxol-5-vh-1-t ' Λ/./V- ςfibυtylaminocarbonylmethyl)-3-(5-te razo}y\)pyrro\\din6 Carbonyldiimidazole (510 mg, 3.148 mmol) was added to 1.020 g (2.00 mmol) of the compound resulting from Example 43 in 2.7 mL THF, and the mixture was heated for 40 minutes at 50 °C. The reaction mixture was cooled in an ice bath, and 25% solution of ammonia in methanol was added. After 30 minutes, the solid which had formed was filtered, washed with ethanol and finally with ether to yield 850 mg (83%) of the 3-carboxamide compound, m.p. 194-196 °C. Phosphorus oxychloride (1.06 g) was added to this amide in 7 mL of pyridine, and the mixture was stirred 1 hour at room temperature. Dichloromethane was added, and the solution was washed with potassium bicarbonate solution, dried over sodium sulfate, and concentrated. The residue was chromatographed on silica gel eluting with 2:1 hexane-ethyl acetate to give 790 mg (96%) of the 3- carbonitrile compound. To this nitrile in 5 mL toluene was added 385 mg of trimethyl tin chloride and 126 mg sodium azide. The mixture was heated 20 hours at 125 °C (bath temp). After cooling, methanol (5 mL ) was added, and the solution was concentrated in vacuo. To the resulting residue was added 6 mL of methanol and 6 mL of water containing 0.2 g phosphoric acid. After stirring 1 hour at room temperature, water was added and the mixture extracted with dichloromethane. The combined organic extracts were dried and concentrated, and the resulting residue was crystallized from ether to give a solid. The solid was dissolved in sodium hydroxide solution, filtered from insoluble material and acidified with acetic acid to get 532 mg (62%) of the title compound, m.p. 165-167 °C. 1 H NMR (CDCI 3 , 300 MHz) δ 0.85 (t, J=7Hz, 3H), 0.87 (t, J=7Hz, 3H), 1.10-1.50 (m, 8H), 3.0-3.6 (m, 8H), 3.70 (s, 3H), 3.7-3.8 (m, 1H), 3.90 (t, J=9Hz, 1H), 4.37 (d, J=9Hz, 1 H), 5.86 (s, 2H), 6.62 (d, J=8Hz, 1 H), 6.65-6.73 (m, 3H), 6.95 (d, J=2Hz, 1 H), 7.11 (d, J=9Hz, 2H). Example 80 trans. frans-2-/4-Fluorophenvn-4-M .3-benzodioxoI-5-vn-1 -fΛ/./V- ry/h<jfv/am/nocarbon mef ή v/)pvrrolidine-3-carboxvlic acid The title compound was prepared as an amorphous solid from methyl (4-flourobenzoyl) acetate and 5-(2-nitrovinyl)-1 ,3- benzodioxole using the procedures described in Examples 1 and 43. 1 H NMR (CDCI3, 300 MHz) δ 0.81 (t, J=7Hz, 3H), 0.90 (t, J=7Hz, 3H), 1.0-1.55 (m, 8H), 2.81 (d, J=13 Hz, 1 H), 2.90-3.10 (m, 4H), 3.15-3.30 (m, 1 H), 3.32-3.45 (m, 3H), 3.55-3.65 (m, 1 H), 3.86 (d, J=10Hz, 1 H), 5.94 (dd, J=2Hz, 4Hz, 2H), 6.72 (d, J=8 Hz, 1H), 6.86 (d, J= 8 Hz, 1 H), 6.95-7.07 (m, 3H), 7.32-7.45 (m, 2H). Example 81 frans.frans-2-f4-Methoxvphenvn-4-M .3-benzodioxol-5-ylV1-fN.N-di.fn- butyπaminomethylcarbonvhpyrrolidine-3-carboxylic acid N.N-Dibutyl glycine (150 mg, 0.813 mmol), prepared by the method of Bowman, R.E., J. Chem. Soc. 1346 (1950), in 0.7 mL of THF was treated with 138 mg (0.852 mmol) carbonyldiimidazole and heated for 30 minutes at 50 °C. After cooling to room temperature, 250 mg (0.678 mmol) of ethyl frans,frans-2-(4-methoxyphenyl)-4-(1 ,3- benzodioxol-5-yl)-pyrrolidine-3-carboxylate, the compound resulting from Example 6A, was added, and the mixture was heated at 45 °C for 30 minutes. The product was chromatographed on silica gel, eluting with 1 :1 hexane-ethyl acetate to give 306 mg of the intermediate ethyl ester. The ester was hydrolyzed with sodium hydroxide in water and ethanol to give 265 mg of the title compound as a white powder. 1 H NMR (CDCI3, 300 MHz) δ rotational isomers - 0.75 and 0.85 (2 t, J=7Hz, 3H), 1.05-1.5 (m, 8H), 2.65-3.20 (m, 6H) 3.43-3.70 (m, 3H), 3.72 (s, 3H), 3.87 (d, J=15Hz, 1 H), 4.49 (dd, J=12Hz, 6Hz) and 5.23 (dd, J=12Hz, 8Hz) 2H, 5.90 (dd, J=2Hz, 4Hz, 2H), 6.63-6.78 (m, 3H), 6.86 and 7.04 (d, J=9Hz, 2H), 7.22 (d, J=9Hz, 2H). Example 82 trans. frans-2-(4-Methoxvphenvn-4-(1.3-benzodioxol-5-yl 1 -f N-n-butyH-N-m- propynaminocarbonvlmethvnpvrrolidine-3-carboxylic acid The title compound was prepared using the procedures described in Example 1. m.p. 160-162 °C. 1 H NMR (CDCI3, 300 MHz) rotational isomers δ 0.69, 0.80, 0.84, 0.87 (four triplets, J=7Hz, 6H), 1.00-1.52 (m, 6H), 2.63 and 2.66 (two doublets, J=13Hz, 1 H), 2.90-3.10 (m, 4H), 3.23- 3.61 (m, 5H), 3.71 and 3.75 (two doublets, J=10Hz, 1 H), 3.78 (s, 3H), 5.92-5.96 (m, 2H), 6.72 (d, J=8Hz, 1 H), 6.83-6.89 (m, 3H), 7.03 (d, J=2Hz, 1H), 7.81 (d, J=9Hz, 2H). Example 83 frans.frans-2-f4-Methoxvphenyn-4-f1.3-benzodioxol-5-vn-1-f2-fN.N-dim- propvnaminocarbonynethvπpvrrolidine-3-carboxvlic acid The compound resulting from Example 6A (250 mg, 0.677 mmol), 205 mg (1.36 mmol) diailyl acrylamide (Polysciences, Inc.), and 10 mg acetic acid were heated at 85 °C in 0.75 mL of methoxyethanol for one hour. Toluene was added, and the solution was washed with bicarbonate solution, dried, and concentrated. Chromatography on silica gel eluting with 3:1 hexane-ethyl acetate gave 283 mg (80%) of the diailyl compound. The diailyl compound was hydrogenated using 10% Pd/C catalyst (27 mg) in ethyl acetate (25 mL) under a hydrogen atmosphere. The catalyst was removed by filtration, and the filtrate was concentrated to afford the dipropyl amide ethyl ester in 100% yield. The ester was hydrolyzed to the title compound by the method of Example 1 D in 83% yield. 1 H NMR (CDCI3, 300 MHz) δ 0.82 and 0.83 (two triplets, J=7Hz, 6H), 1.39-1.54 (m, 4H), 2.35-2.60 (m, 3H), 2.80-3.07 (m, 5H), 3.14-3.21 (m, 2H), 3.31 -3.38 (m, 1 H), 3.51-3.61 (m, 1 H), 3.73 (d, J=12H, 1H), 3.75 (s, 3H), 5.94 (s, 2H), 6,71 (d, J=9Hz, 1 H), 6.79-6.85 (m, 3H), 7.04 (d, J=2Hz, 1H)< 7.32 (d, J=9Hz, 2H). Example 84 frans.frans-2-f4-Methoxyphenvn-4-n.3-benzodioxol-5-yl)-1-fN.N-dim- butynaminocarbonyhpyrrolidine-3-carboxylic acid The title compound was prepared by the procedures described in Example 8 using dibutyl carbamoyl chloride, prepared by the method of Hoshino et al., Syn. Comm., 17: 1887-1892 (1987), as a starting material. 1 H NMR (CDCI 3 , 300 MHz) δ 0.86 (t, J=7Hz, 6H), 1.14-1.28 (m, 4H), 1.35-1.48 (m, 4H), 2.81-2.94 (m, 2H), 3.11 (t, J=12Hz, 1H), 3.30- 3.41 (m, 2H), 3.59-3.68 (m, 2H), 3.76 (s, 3H), 3.78-3.85 (m, 1H), 5.81 (d, J=9Hz, 1H), 5.94 (s, 2H), 6.73-6.86 (m, 5H), 7.24 (d, J=9Hz, 2H). Example 85 trans. fraπs-2- 4-Methoxyphenyn-4-M .3-bβnzodioxol-5-v -1 -/Λ/ V- /ϋ ffy/am/nocarbon mefή )pyrrolidine-3-carboxylic acid sodium salt Sodium hydroxide (48.2 mg of 98.3% pure, 1.184 mmol) in 2 mL of MeOH was added to the compound resulting from Example 43 (610 mg, 1.196 mmol.) in 5 mL MeOH. The solution was concentrated to dryness, and the resulting powder was stirred with heptane. The heptane was removed in vacuo to give a powder which was dried in the vacuum oven for 2 hours at 60 °C to yield 627.5 mg of the title compound. Example 86 frans.frans-2-f4-Methoxyphenyn-4-M .3-benzodioxol-5-yn-1-f2-,N.N-dim- butvnaminotethyllPvrrolidine-3-carboxylic acid A solution of the bromoethyl compound resulting from Example 61 A (150 mg), dibutylamine (150 mg) and sodium iodide (18 mg) in 0.75 mL ethanol was heated at 80 °C for 1 hour. After cooling, toluene was added, and the solution was washed with potassium bicarbonate solution, dried over Na2S04 and concentrated. More toluene was added, and the solution was again concentrated to get rid of excess dibutylamine. The residue was dissolved in warm heptane and filtered from a small amount of insoluble material. The hepane was removed in vacuo to give 143 mg (87%) of the intermediate ethyl ester. The ester was hydrolyzed by the method of Example 1D to give the title compound as a white powder. 1 H NMR (CD 3 OD, 300 MHz) δ 0.89 (t, J=7Hz, 6H), 1.16-1.30 (m, 4H), 1.44-1.56 (m, 4H), 2.48-2.57 (m, 1 H), 2.80-3.08 (m, 8H), 3.14-3.25 (m, 1H), 3.31-3.38 (m, 1H), 3.59-3.60 (m, 1 H), 3.74 (s, 3H), 3.75 (d, J=10Hz, 1 H), 5.89 (s, 2H), 6.71 (d, J=9Hz, 1 H), 6.81 (dd, J=9Hz, 2Hz, 1H), 6.90 (d, J=10Hz, 2H), 6.96 (d, J=2Hz, 1 H), 7.37 (d, J=10Hz, 2H). 5 Example 87 frans. frans-2-f4-Methoχyphenvπ-4-f1.3-benzodioxol-5-vn-1-(2-rN-fN.N-dim- butynaminocarbonvn-N-methvlamino1ethvl pvrrolidine-3-carboxvlic acid Dibutyl carbamoyl chloride (135 mg) was added to the compound resulting from Example 61 B (250 mg) and 150 mg triethylamine in 1 mL ι o dichloromethane. After stirring 1 hour at room temperature, toluene was added, and the solution was washed with potassium bicarbonate solution, dried over Na2Sθ4 and concentrated. The residue was chromatographed on silica gel, eluting with a mixture of 38% EtOAc and 62% hexane to give 194 mg of the ethyl ester intermediate. i s The ester was hydrolyzed by the method of Example 1 D to afford 141 mg of the title compound. 1 H NMR (CD 3 OD, 300 MHz) δ 0.92 (t, J=7Hz, 6H), 1.21-1.32 (m, 4H), 1.42-1.53 (m, 4H), 2.62 (s, 3H), 2.65-2.76 (m, 1H), 3.00-3.20 (m, 8H), 3.44-3.55 (m, 1 H), 3.62-3.78 (m, 2H), 3.80 (s, 3H), 4.07 (d, J=12 Hz, 1 H), 5.93 (s, 2H), 6.75 (d, J=9Hz, 1 H), 6.87 (dd, 20 J=9Hz, 2Hz, 1H), 6.94 (d, J=10 Hz, 2H), 7.04 (d, J=2Hz, 1 H), 7.40 (d, J=10Hz, 2H). Example 88 frans.frans-2-f4-MethoxvphenvlV4-f1.3-benzodioxol-5-vn-1-fN.N-dim- 25 butvnaminocarbonvnmethvhpvrrolidine-3-fN-methanesulfonyncarboxamide Carbonyldiimidazole (75 mg, 0.463 mmol) was added to 150 mg (0.294 mmol) of the compound resulting from Example 43 in 0.4 mL of tetrahydrofuran, and the solution was stirred at 60 °C for 2 hours. After cooling, 50 mg (0.526 mmol) of methanesulfonamide and 68 mg 30 (0.447 mmol) of DBU in 0.3 mL of THF were added. The mixture was stirred at 45 °C for 2 hours. The solvents were removed in vacuo, and the residue was dissolved in water. A few drops of acetic acid were added, and the solution was lyophilized to give 121 mg (70%) of the title compound, m.p. 170-173 °C. 1 H NMR (CDCI3, 300 MHz) δ 0.82 (t, 35 J=7Hz, 3H), 0.88 (t, J=7Hz, 3H), 1.05-1.51 (m, 8H), 2.75-2.86 (m, 2H), 2.83-3.25 (m, 4H), 3.17 (s, 3H), 3.32-3.50 (m, 3H), 3.70-3.78 (m, 1 H), 3.80 (s, 3H), 3.87 (d, J=10Hz, 1 H), 5.96 (dd, J=2Hz, 4Hz, 2H), 6.74 (d, J=9Hz, 1 H), 6.84 (dd, J=9Hz, 2Hz, 1H), 6.90 (d, J=10 Hz, 2H), 7.01 (d, J=2Hz, 1H), 7.34 (d, J=10Hz, 2H). Example 89 5 frans. frans-2-f4-Methoxv p henvn-4-π .3-benzodioxol-5-vn-1-fN.N-difn- butvnaminocarbonvnmethvhPvrrolidine-3-fN-benzenesulfonyncarboxamide The compound resulting from Example 43 was converted to the title compound by the method of Example 88 substituting benzenesulfonamide for methanesulfonamide. m.p. 169-171 °C for a ι o sample recrystallized from acetonitrile. 1 H NMR (CDCI3, 300 MHz) δ 0.81 (t, J=7 Hz, 3H), 0.89 (t, J=7Hz, 3H), 1.02-1.50 (m, 8H), 2.65-2.80 (m, 2H), 2.90-3.25 (m, 4H), 3.80-3.95 (m, 3H), 3.50-3.60 (m, 1 H), 3.65 (d, J=10Hz, 1H), 3.81 (s, 3H), 5.94 (s, 2H), 6.70 (s, 2H), 6.81-6.90 (m, 3H), 7.17 (d, J=10Hz, 2H), 7.55 (t, J=7 Hz, 2H), 7.66 (t, J=7Hz, 1H), 8.95 (d, 15 J=7Hz, 2H). Example 90 frans.frans-2-(4-Methoxvphenvn-4-(1.3-benzodioxol-5-vlV1-rN.N-dirn-butvn aminosulfonylmethyl]-pyrrolidine-3-carboxylic acid 20 Chloromethyl sulfenyl chloride, prepared by the method of Brintzinger et. al., Chem. Ber. £5_: 455-457 (1952), is reacted with dibutylamine by the method of E. Vilsmaier described in Liebigs Ann. Chem. 1055-1063 (1980) to give N,N-dibutyl chloromethyl sulfenyl chloride. Alternatively dimethyl(methylthio)sulfonium 25 tetraflouroborate is reacted with dibutylamine to give N,N-dibutyl methylsulfenyl chloride which is chlorinated with N-chlorosuccinimide to give chloromethyl sulfenyl chloride by the method of E. Vilsmaier, described in the above reference. The N,N-dibutyl chloromethyl sulfenyl chloride is reacted with 30 the compound resulting from Example 6A to give ethyl trans, trans-2- (4-Methoxyphenyl)-4-(1 ,3-benzodioxol-5-yl)- 1 -[N,N-di(n- butyl)aminosulfenylmethyl]-pyrroIidine-3-carboxylate. This is oxidized with osmium tetroxide and N-methyl morpholine N-oxide by the method of S. Kaldor and M. Hammond, Tet. Lett. 2£: 5043-5045 35 (1991 ) to give the title compound after hydrolysis of the ethyl ester. Example 91 frans.frans-2-f4-Methoxyphenyn-4-n .3-benzodioxol-5-yn-1-[fN.N- dibutylamino)carbonyl-1 - RS ethyllpyrrolidine-3-carboxylic acid Example 91 A (±VDibutvl 2-bromoproρanamide 2-Bromopropanoic acid (510 mg, 3.33 mmol) and 4-methylmorpholine (0.74 mL, 6.73 mmol) were dissolved in 10 mL of CH2CI2, the solution was cooled to 0 °C under a N2 atmosphere, and then treated dropwise with isobutyl chloroformate (0.45 mL , 3.5 mmol). After 10 minutes at 0 °C, dibutylamine (0.57 mL, 3.4 mmol) was added. The reaction was stirred at 0 °C for 1 hour and for an additional 16 hours at room temperature. The mixture was partitioned with 25 mL of 1.0 M aqueous Na2Cθ3 solution, then the organic phase was washed sequentially with 25 mL of 1 M aqueous NaHSθ4 and 25 mL brine, dried (Na2Sθ4), filtered, and concentrated under reduced pressure to afford 698 mg (2.64 mmol, 79 %) of the crude bromoamide as a colorless oil. 1 H NMR (CDCI3, 300 MHz) δ 0.93 (t, J=7Hz) and 0.97 (t, J=7.5Hz, 6H total), 1.26-1.60 (m, 7H), 1.60-1.78 (m, 1H), 1.82 (d, J=6Hz, 3H), 3.04-3.27 (m, 2H), 3.42-3.64 (m, 2H), 4.54 (q, J=7H, 1H). MS (DCI/NH3) m/e 264 and 266 (M+H) + . Example 91 B trans.trans- and c/s.frans^-U-Methoxyphenyl -f 1.3-benzodioxol-5-vn-1-rfN.N- dibutylamino carbonyl-1-fffSVethynpvrrolidine-3-carboxylic acid ethyl ester A solution of the resultant mixture of trans.trans and cis.trans compounds from Example 1C (232 mg, 0.628 mmol) and the resultant compound from Example 91 A (183 mg, 0.693 mmol) in 2 mL of CH3CN was treated with diisopropylethylamine (0.22 mL, 1.3 mmol). The solution was stirred at 60-80 °C under a N2 atmosphere for 16 hours. The reaction was concentrated under reduced pressure, then the residue was partitioned between 30 mL Et2θ and 10 mL of 1 M aqueous Na2Cθ3 solution. The organic phase was washed with 20 mL water and 20 mL brine, dried over Na2Sθ4, filtered and concentrated under reduced pressure to afford the crude amino amide as a brown oil (339 mg, 98% crude). The product was obtained by flash chromatography on silica gel eluting with 20% EtOAc-hexane to provide 224 mg (70%) of the title compounds as a mixture of 4 diastereomers. H NMR (CDCI3, 300 MHz) δ 0.66-1.55 (several m, 19H), 2.63- 3.00 (m, 3H), 3.05-3.39 (m, 2H), 3.40-3.76 (m, 4H), 3.78-3.80 (4 s, 3H), 3.84-4.25 (m, 2.6H), 4.38 (d, J=10.5Hz, 0.2H) and 4.58 (d, J=10.5Hz, 0.2H), 5.90-5.97 (m, 2H), 6.68-6.96 (m, 5H), 7.38-7.43 (m, 2H). MS (DCI/NH3) m/e 553 (M+H)+. Example 91 C frans.frans-2-f4-Methoxv p henvl,-4-f1.3-benzodioxol-5-vn-1-ffN.N- dibutylamino)carbonyl-1-(/=?S)-ethyl)pyrrolidine-3-carboxylic acid The procedure of Example 73C was used, substituting the resultant compound from Example 91 B for the resultant compound from Example 73B to give the title compound in 61% yield. 1 H NMR (CD3OD, 300 MHz) δ 0.70-1.05 (several , 8H), 1.14 (d, J=6Hz, 2H), 1.17-1.55 (m, 6H), 2.79-3.03 (m, 3.5H), 3.20-3.65 (br m, 4.6H plus CD2HOD), 3.70-3.78 (m, 0.4H), 3.79 (s, 3H), 3.98 (d, J=8Hz, 0.6H), 4.06 (t, J=7.5Hz, 0.4H), 4.25 (d, J=8Hz, 0.4H), 5.92 (s) and 5.94 (s, 2H total 6H), 6.73 (d, J=2.5Hz) and 6.75 (d, J=3Hz, 1H total), 6.78-6.85 (m, 1 H), 6.91-7.00 (m, 3H), 7.30- 7.38 (m, 2H). MS (DCI/NH3) m/e 525 (M+H) + . Anal calcd for C30H40N2O6 O.5H2O: C, 67.52; H, 7.74; N, 5.25. Found: C, 67.63; H, 7.65; N, 5.21. Example 92 frans. frans-2-f Pentyn-4-π .3-benzodioxol-5-yn-1-fN.N- dibutylaminocarbonylmethynpyrrolidine-3-carboxylic acid Example 92A Methyl 2-,4-hexenoyn-4-nitro-3-M .3-benzodioxole-5-ynbutyrate A solution of methyl 3-oxo-6-octenoate (502 mg, 2.95 mmol) in 10 mL of isopropanol was added to a solution of 5-(2-nitrovinyl)-1,3-benzodioxole (712 mg, 3.69 mmol) in 10 mL THF, then DBU (22 μL, 0.15 mmol) was added. The resulting reddish solution was stirred at room temperature for 20 minutes. TLC (ethyl acetate-hexane, 1 :3) indicated complete consumption of ketoester. The solution was concentrated in vacuo and flash chromatographed on silica gel eluting with 18% ethyl acetate in hexane to produce 879 mg (2.42 mmol, 82%) of the title compound as a mixture of diastereomers in a 1:1 ratio. 1 H NMR (CDCI3, 300 MHz) δ 1.55-1.66 (m, 3H), 2.02-2.17 (br m, 1 H), 2.20-2.37 (m, 1.5H), 2.49-2.76 (m, 1.5H), 3.57 (s, 1.5H), 3.74 (s, 1.5H), 3.97 (d, J=7.5H, 0.5H) and 4.05 (d, J =8Hz, 0.5H), 4.10-4.20 (m, 1 H), 4.68-4.82 (m, 2H), 5.06-5.52 (m, 2H), 5.95 (2s, 2H), 6.65 (m, 1H), 6.68 (br s, 1 H), 6.75 (d, 7.5Hz, 1H). MS (DCI/NH3) m/e 381 (M+NH 4 ) + . Anal calcd for C18H21NO7: C, 59.50; H, 5.82; N, 3.85. Found: C, 59.32; H, 5.71; N, 3.72. Example 92B Methyl trans. rans-2-f pentvn-4-n .3-benzodioxol-5-vnpvrrolidine-3-carboxylate The procedures of Example 1 B and Example 1C were followed, with the substitution of the resultant compound from Example 92A for the resultant 5 compound from Example 1A, and the substitution of the this resultant compound for the resultant compound from Example 1B, to provide the title compound in crude form as a yellow oil. This crude compound was epimerized under the following conditions. A solution of the crude compound (660 mg, 2.07 mmol) in 3 mL methanol was treated with a solution of sodium methoxide (made by the addition of o sodium metal (14 mg, 0.61 mmol) to 1 mL of methanol). The resultant solution was heated at reflux for 18 hours. The reaction was concentrated under reduced pressure, and the residue was partitioned between 25 mL saturated NaHCθ3 diluted with 10 mL water and 30 mL of CH2CI2. The aqueous phase was extracted (2 x 30 mL CH2CI2), then the combined organic phases were washed with 20 mL 5 brine, dried over Na2SO , filtered and the filtrate concentrated under reduced pressure to afford the crude product. Purification by flash chromatography on silica gel eluting with 3.5% methanol in CH2CI2 gave 336 mg (57%) the title compound as a yellow oil. " Η NMR (CDCI3, 300 MHz) δ 0.90 (br t, 3H), 1.25-1.70 (br m, 8H), 1.83-2.02 (br s, 2H), 2.58 (dd, J=8,9Hz, 1H), 2.99 (dd, J=8,14Hz, 1H), 3.34-3.45 (m, 0 2H), 3.53 (q, J=9Hz, 1H), 3.66 (s, 3H), 5.94 (s, 2H), 6.65-6.75 (m, 3H). MS (DCI/NH3) m/e 320 (M+H) + . Anal calcd for C18H25 O4: C, 67.69; H, 7.89; N, 4.39. Found: C, 67.39; H, 7.84; N, 4.37. Example 92C 5 frans.frans-2-f Pentyl)-4-f 1.3-benzodioxol-5-yn-1 -(N.N- dibutylaminocarbonylmethyl)pyrrolidine-3-carboxylic acid The procedures of Example 1B-1 D were used, with the substitution of the resultant compound from Example 92A for the resultant compound from Example 1B, to provide the title compound as a white foam. 1 H NMR (CDCI3, 300 MHz) δ 0 0.87 (br t) and 0.89 (br t, 6H total), 0.97 (t, J=7.5Hz, 3H), 1.21-1.42 (br m, 10), 1.43- 1.78 (br , 6H), 2.76 (t, J=7Hz, 1H), 3.02-3.30 (br m, 6H), 3.40-3.60 (m, 3H), 3.73 (d, J=14Hz, 1 H), 5.98 (AB, 2H), 6.70 (d, J=7Hz, 1H), 6.77 (dd, J=1.5,7Hz, 1 H), 6.89 (d, J=1.5Hz, 1H). MS (DCI/NH3) m/e 475 (M+H) + . Anal calcd for C-27H42N2O5 O.5H2O: C, 67.05; H, 8.96; N, 5.79. Found: C, 67.30; H, 8.77; N, 5.68. 5 Example 93 frans.frans-2-fPentvn-4-n .3-benzodioxol-5-yn-1-f2-fN-propyl-N- ρropvlsulfonvlamino)ethvl)pyrrolidine-3-carboxylic acid 5 Example 93A Methyl trans. frans-2-fpentvn-4-f1.3-benzodioxol-5-vn-1-f2-bromoethynpyrrolidine- 3-carboxvlate The procedure of Example 61 A was used, with the substitution of the resultant compound from Example 92B for the resultant compound from Example ι o 1 C, to provide the title compound as a yellow oil. 1 H NMR (CDCI3, 300 MHz) δ 0.89 (br , J=7Hz, 3H), 1.24-1.40 (br m, 6H), 1.60-1.80 (br m, 2H), 2.61-2.75 (m, 2H), 2.76-2.91 (m, 2H), 3.10-3.22 (m, 2H), 3.36-3.47 (m, 2H), 3.68 (s, 3H), 5.92 (s, 2H), 6.69-6.77 (m, 2H), 6.90-6.94 (m, 1 H). MS (DCI/NH3) m/e 426, 428 (M+H) + . 15 Example 93B propylsulfonylamino)ethyllpyrrolidine-3-carboxylate A solution of the resultant compound from Example 93A (102 mg, 0.24 mmol) and tetrabutylammonium iodide (6 mg, 16 μ ol) in 1 mL EtOH was treated with 20 propylamine (60 μL, 0.73 mmol). The solution was warmed to 80 °C for 4 hours. The reaction was concentrated under reduced pressure, then the residue was dissolved in 35 mL ethyl acetate and extracted with 2 x 15 mL of 1 M aqueous Na2Cθ3. The organic phase was washed with 15 mL brine, then dried over Na2Sθ4, filtered and concentrated under reduced pressure to provide the crude 25 secondary amine as a yellow oil (94.2 mg). The crude amine was dissolved in 1 mL of CH2CI2, diiosopropylethylamine (65 μL, 0.373 mmol) was added, followed by propylsulfonyl chloride (29 μL, 0.26 mmol). The solution was stirred at room temperature for 4 hours. The reaction was quenched with 10% aqueous citric acid (to pH 4), and the mixture was extracted with 2 x 3 mL CH2CI2- The combined 30 organic extracts were washed with 2 mL brine, then dried over Na2S04, filtered, concentrated in vacuo. Purification by flash chromatography eluting with 20% ethyl acetate in hexane provided 65.0 mg (53%) of the title compound as a waxy solid. Rf = 0.17 (20%EtOAc-hexane). MS (DCI/NH3) m/e 511 (M+H) + . Exa pie 93C frans. frans-2-fPentvn-4-M .3-benzodioxol-5-vh-1-r2-(N-propyl-N- propylsulfonvlaminotethyl]pyrrolidine-3-carboxvlic acid The procedure of Example 71 C was followed, with the substitution of the resultant compound from Example 93B for the resultant compound from Example 71 B, to provide the title compound as a white foam (47 mg, 80%), Rf = 0.14 (5%MeOH-CH 2 CI 2 ). 1 H NMR (CDCI 3 , 300 MHz) δ 0.88 (br t) and 0.92 (t, J=7Hz, 6H total), 1.22-1.52 (br m, 6H), 1.63 (sextet, J=8Hz, 2H), 1.75-2.10 (br m, 4H), 2.89-2.98 (m, 2H), 3.05 (br t, J=9Hz, 1 H), 3.10-3.30 (m, 3H), 3.30-3.80 (br m, 7H), 5.94 (s, 2H), 6.71 (t, J=8Hz, 1 H), 6.77 (dd, J=1.5,8Hz, 1 H), 6.89 (d, J=1.5Hz, 1 H). MS (DCI/NH3) m/e 497 (M+H)+. Example 94 frans. frans-2-fPropvn-4-f1.3-benzodioxol-5-yn-1-rN.N- dibυtylaminocarbonylmethynpyrrolidine-3-carboxylic acid Example 94A Ethyl 2-f4-butanovn-4-nitro-3-(1.3-benzodioxole-5-ynbutyrate The procedure of Example 92A was followed, with the substitution of ethyl butyryl acetate for methyl 3-oxo-6-octenoate, to provide the title compound as a mixture of trans and cis isomers (47 mg, 80%), Rf = 0.28 (25%EtOAc-hexane). 1 H NMR (CDCI3, 300 MHz) δ 0.74 (t, J=7.5Hz) and 0.91 (t, J=7.5Hz, 3H total), 1.08 (t, J=7Hz) and 1.28 (t, J=7Hz, 3H total), 1.45 (sextet, J=7Hz, 1.5H), 1.63 (sextet, J=7Hz, approx. 1.5H), 2.17 (t, J=7Hz) and 2.24 (t, J=7Hz, 0.5H total)2.40-2.54 (m, 1H), 2.60 (t, J=7.5Hz) and 2.67 (t, J=7.5Hz, 0.5H total), 3.93-4.09 (m, 2H), 4.10-4.20 (br m, 1H), 4.23 (q, J=7Hz, 1H), 4.67-4.85 9m, 2H), 5.94 (s, 2H), 6.62-6.75 (m, 3H). MS (DCI/NH3) m/e 369 (M+NH 4 ) + . Anal calcd for C17H21 N0 7 : C, 58.11 ; H, 6.02; N, 3.99. Found: C, 58.21 ; H, 5.98; N, 3.81. Example 94B Ethyl frans.frans-2-fpro p vn-4-M .3-benzodioxol-5-vn p vrrolidine-3-carboxylate The procedure of Example 92B was followed, with the substitution of the resultant compound from Example 94A for the resultant compound from Example 92A, to afford the title compound. MS (DCI/NH3) m/e 306 (M+H)+. Example 94C frans. frans-2-f PropvlV4-f1.3-benzodioxol-5-vn-1 -( (N.N- dibutylamino^carbonvnmethvlPvrrplidine-3-carboxylic acid The procedure of Example 92C was followed, with the substitution of the resultant product from Example 94B for the resultant product from Example 92B, to give the title compound. 1 H NMR (CDCI 3 , 300 MHz) δ O.βg (t, J=7.5Hz), 0.92 (t, J=7.5Hz), and 0.97 (t, J=7.5H, 9H total), 1.22-1.80 (br m, 12H), 2.83 (t, J=7.5Hz, 1H), 3.40-3.55 (br m, 2H), 3.55-3.68 (m, 1H), 3.78 (d, J=15Hz, 1H), 5.92 (q, J=1 Hz, 2H), 6.70 (d, J=8Hz, 1H), 6.79 (dd, J=1 Hz,8Hz, 1 H), 6.90 (d, J=1Hz, H). MS (DCI/NH3) m/e 447 (M+H) + . Anal calcd for C25H38N2O5 O.5 H 2 0: C, 65.91 ; H, 8.63; N, 6.15. Found: C, 65.91 ; H, 8.68; N, 5.94. Example 95 f2R.3R.4S)-M-2- 4-MethoxyDhenvn-4-n .3-benzodioxol-5-yli-1-ftert- butyloxycarbonyl-aminocarbonvlmethvn-pvrrolidine-3-carboxylic acid Example 95A frans.frans-2-f4-Methoxyphenvn-4-π .3-benzodioxol-5-vn-1-fftert- butyloxycarbonylaminocarbonylmethyl]pyrrolidine-3-carboxylic acid The resulting mixture of 64% trans. trans- and cis.trans- pyrrolidines resulting from Example 1C (3.01 g, 8.15 mmol) was dissolved in 50 mL of methylene chloride. To this was added dropwise a solution of di-tert-butyl dicarbonate (1.96 g, 8.97 mmol) in 20 mL methylene chloride under a nitrogen atmosphere, and the resulting solution was stirred 30 minutes at which point TLC (ethyl acetate:hexane, 1 :1 ) indicated that all of the starting material was consumed. The reaction mixture was concentrated and dried under high vacuum to give 3.94 g of the ethyl ester as a yellow-brown oil. 1 H NMR (CDCL3, 300 MHz) δ 0.99, 1.07 (br t, br t, J=7 Hz, 3H), 1.11-1.62 (several br m, 9H), 3.05 (br m, 1 H), 3.44-3.95 (m, 3H), 3.81 (s, 3H), 4.04 (q, J=7 Hz, 1 H), 4.14-4.28 (br m, 1 H), 4.89-5.24 (br m, 1 H), 5.94 (d, J=3 Hz, 2H), 6.69-6.90 (m, 5H), 7.06-7.20 (m, 2H). MS (DCI/NH3) m/e 470 (M+H)+. To the ethyl ester dissolved in 170 mL of ethanol was added a solution of lithium hydroxide (1 .06 g, 25.17 mmol) in 60 mL of water. The reaction mixture was vigorously stirred for 18 hours under a nitrogen atmosphere. The reaction mixture was concentrated to remove ethanol, diluted with 250 mL of water and extracted three times with 250 mL of ether. The organic phase acidified to slight cloudiness (pH -7) with 1 hydrochloric acid, then to pH 4 with 10 % citric acid and extracted with 5 % ethanol in methylene chloride (3 x 100 mL). The combined organic layers dried (Na2S04), filtered, concentrated and dried on high vacuum to give the title compound as a white foam (2.19 g, 60 %). 1 H NMR (CDCI3, 300 MHz) δ 1.16 (v br s, 9H), 3.11 (br m, 1H), 3.50-3.64 (m, 2H), 3.81 (s, 3H), 4.24 (br m, 1H), 4.96 (br m, 1H), 5.94 (s, 2H), 6.71-6.79 (m, 3H), 6.84-6.91 (m, 2H), 7.19 (d, J=9 Hz, 2H). MS (DCI/NH 3 ) m/e 442 (M+H) + . Example 95B f2R.3R.4SVf+V2-r4-Methoxvohenvn-4-n.3-benzodioxol-5-vh-1-ftert- butyloxycarbonylaminocarbonyimethvn-Pvrrolidine-3-carboxylic acid The compound resulting from Example 95A (2.15 g, 4.86 mmol) and (+)-cinchonine (1.43 g, 4.86 mmol) were added to 100 mL of methylene chloride; this suspension was swirled with warming as necessary to get ail solids to dissolve. The solution was then concentrated and dried on high vacuum to a white foam. This material was crystallized from a mixture of refluxing chloroform (64 mL) and hexane (360 mL). The resulting crystals were isolated by filtration and recrystaliized under the same conditions seven additional times. Each time the resulting crystals and filtrate were monitored by 1 H NMR and chiral HPLC. The amount of (2S,3S,4R)-(-)- enantiomer decreased first in the crystals and then in the filtrate with the predetermined endpoint achieved when the (2S,3S,4R)-(-)- enantiomer could no longer be detected in the filtrate. The pure (2R,3R,4S)-(+)- enantiomer thus obtained was partitioned between 100 mL of 10% citric acid and 100 mL of ether. The aqueous layer was further extracted twice with 100 mL of ether. The combined ether layers were washed with brine, dried (Na2Sθ4), filtered, concentrated and dried on high vacuum to a white powder (550 mg, 55 % of theoretical 50 % maximum, >99.5 ee). 1 H NMR (CDCI3, 300 MHz) δ 1.05-1.50 (br m, 9H), 3.12 (br m, 1 H), 3.50-3.65 (m, 2H), 3.81 (s, 3H), 4.24 (m, 1H), 4.96 (br m, 1H), 5.95 (s, 2H), 6.70-6.79 (m, 3H), 6.86 (d, J=9 Hz, 2H), 7.19 (d, J=9 Hz, 2H). MS (DCI/NH3) m/e 442 (M+H) + . Example 95C (2R.3R.4SW+VEthvl 2-(4-methoxvphenvl)-4-M.3-benzodioxol-5-yπ-pyrrolidine-3- carboxvlate The compound resulting from Example 95B (251 mg, 0.568 mmol) was dissolved in 20 mL of a saturated solution of anhydrous HCI(g) in anhydrous ethanol. The resulting solution was heated at 50 °C. with stirring for 18 hours at which point all of the precipitated solid had dissolved. The reaction mixture was concentrated to a solid which was partitioned between 0.8 M aqueous sodium carbonate (50 mL) and methylene chloride (50 mL). The aqueous layer was further extracted with methylene chloride (2 x 50 mL). The combined organic layers were dried (Na2Sθ4), filtered, concentrated and dried under high vacuum to give the title compound as an almost colorless oil (158 mg, 69%). 1 H NMR (CDCI 3 , 300MHz) δ 1.11 (t, J=7 Hz, 3H), 2.18 (v br s, 1H), 2.93 (t, J= 9 Hz, 1H), 3.19,3.22 (dd, J=7 Hz, 1H), 3.50-3.69 (m, 2H), 3.80 (s, 3H), 4.07 (q, J=7 Hz, 2H), 4.49 (d, J=g Hz, 1H), 5.g4 (s, 2H), 6.73 (d, J=2 Hz, 2H), 6.81-6.92 ( , 3H), 7.34-7.41 (m, 2H). MS (DCI/NH3) m/e 370 (M+H)+. Example 95D f2R.3R.4S»-M-2-(4-Methoxyphenyn-4-M.3-benzodioxol-5-ylV1-(tert- butyloxycarbonyl-aminocarbonylmethyl)-pyrrolidine-3-carboxylic acid To the resulting compound from Example 95C (131 mg, 0.355 mmol) was added, diisopropylethylamine (137 mg, 185 μL, 1.06 mmol), acetonitrile (2 mL), N,N-di-(n-butyl)bromoacetamide (133 mg, 0.531 mmol), and the mixture was heated at 50 °C. for 1.5 hours. The reaction mixture was concentrated to a solid, dried under high vacuum, and purified by chromatography on silica gel eluting with 1:3 ethyl acetate-hexane to give pure ester as a colorless oil. 1 H NMR (CDCI3, 300MHz) δ 0.81 (t, J=7 Hz, 3H), 0.88 (t, J=7 Hz, 3H), 1.10 (t, J=7 Hz, 3H), 1.00-1.52 (m, 8H), 2.78 (d, J=14 Hz, 1 H), 2.89-3.10 (m, 4H), 3.23-3.61 (m, 5H), 3.71 (d, J=9 Hz, 1H), 3.80 (s, 3H), 4.04 (q, J=7 Hz, 2H), 5.94 (dd, J=1.5 Hz, 2H), 6.74 (d, J=9 Hz, 1H), 6.83-6.90 (m, 3H), 7.03 (d, J=2 Hz, 1H), 7.30 (d, J=9 Hz, 2H). MS (DCI/NH3) m/e 539 (M+H) + . To the ethyl ester dissolved in 7 mL of ethanol was added a solution of lithium hydroxide (45 mg, 1.06 mmol) in water (2.5 mL). The mixture was stirred for 1 hour at ambient temperature and then warmed slowly to 40 °C. over 2.5 hours at which point all of the starting material had been consumed. The reaction mixture was concentrated to remove the ethanol, diluted with 60 mL water and extracted with ether (3 x 40 mL). The aqueous solution was treated 5 with 1 N. aqueous hydrochloric acid until cloudy, and the pH was then adjusted to -4-5 with 10% aqueous citric acid. This mixture was extracted with 1 :19 ethanol-methylene chloride (3 x 50 mL). The combined extracts were dried (Na2S04), filtered, concentrated and dried under high vacuum to give the title compound as a white foam (150 mg, ι o 83%). 1H NMR (CDCI 3 . 300MHz) δ 0.80 (t, J=7 Hz, 3H), 0.88 (t, J=7 Hz, 3H), 1.08 (m, 2H), 1.28 (m, 3H), 1.44 (m, 3H), 2.70-3.77 (svr br m, 12H), 3.79 (s, 3H), 5.95 (m, 2H), 6.75 (d, J=8 Hz, 1 H), 6.87 (br d, J=8 Hz, 3H), 7.05 ( br s, 1 H), 7.33 (v br s, 2H). MS (DCI/NH 3 ) m/e 511 (M+H)+. [α]22 = +74.42°. Anal calcd for C29H38N2O6 -0.5 H 2 0: C ,67.03; H, 7.56; N, 15 5.39. Found: C, 67.03; H, 7.59; N, 5.33. Example 95 E Alternate Preparation of f2R.3R.4S f+V2-f4-Methoxvphenv -4-n.3-benzodioxol-5- yn-1-ftert-butyloxycarbonylaminocarbonylmethvπ-pyrrolidine-3-carboxylic acid 20 The product of Example 95A (2.858 g) was suspended in 10 mL of EtOAc. 0.7833 g of R (+) alpha methyl benzylamine in 3 mL ethyl acetate was added. On swirling ail of the solids were dissolved. The ethyl acetate was removed in vacuum. Ether (13 ml) was added to the residue. When all of the residue had dissolved, 5 mg of seed crystals 25 were added and these crystals were crushed with a metal spatula while cooling in ice. The product crystallized very slowly. After 1 hour the solid was filtered and washed with ether giving 1.4213 g, m.p. 163- 167°. The filtrate was concentrated, cooled and scratched with a spatula to give a second crop 0.1313 g, m.p. 164-168°. The filtrate 30 was concentrated again and put in the refrigerator and let stand overnight giving 1.6906 g, m.p. 102-110°. (HPLC of this showed 20%of the desired enantiomer and 80% of the unwanted enantiomer.) The first two batches of crystallized material were combined and suspended in 20 mL dichloromethane (Note: the unwanted isomer is 35 more soluble in dichloromethane) and stirred for 2 minutes. The mixture was concentrated, but not to dryness, and ether (10 mL) was added. After stirring for a few minutes the crystals were filtered. Yield: 1.401 g, m.p. 164-172°. Treatment of the crystalline product with 10% citric acid and ether according the method described in Example 95B provided the title compound. Example 96 frans.frans-2-f4-Methoxv p henyn-4-f1.3-benzodioxol-5-vn-1-f2-fN-propyl-N- ι o butyrylaminθ)ethyllpyrrolidine-3-carboxylic acid The title compound was prepared by the methods described in Example 61 , but substituting propylamine for methylamine in Example 61 B and butyryl chloride for isobutyryl chloride in Example 61 C. The product was purified by preparative HPLC (Vydac μC18) eluting with a 15 10-70% gradient of CH3CN in 0.1 % TFA. The desired fractions were lyophilized to give the product as a white solid. 1 H NMR (CDCI3, 300 MHz) δ 0.80 (m, 3H), 0.90 (t, 3H, J=8Hz), 1.42 (m, 2H), 1.58 (heptet, 2H, J=8Hz), 2.20 (t, 3H, J=8Hz), 2.94 (br m, 2H), 3.10 (br m, 2H), 3.48 (br m, 4H), 3.76 (br m, 2H), 3.78 (s, 3H), 4.30 (br s, 1H), 5.95 (s, 2H), 6.75 (d, 20 1H, J=8Hz), 6.84 (m, 1 H), 6.85 (d, 2H, J=8Hz), 7.04 (d, 1 H, J=1 Hz), 7.40 (d, 2H, J=8Hz). MS (DCI/NH3) m/e 497 (M+H) + . Anal calcd for C28H36N2O6 ■ 1.0 TFA: C, 58.82; H, 6.42; N, 4.57. Found: C, 58.77; H, 6.30; N, 4.42. Example 97 25 frans.frans-2-(4-Methoxyphenvn-4-f1.3-benzodioxol-5-vlV1-r2-fN-propvl-N- fethylaminocarbonynamino)ethyHPvrrolidine-3-carboxvlic acid The title compound was prepared by the methods described in Example 61 , but substituting propylamine for methylamine in Example 61 B and ethyl isocyanate for isobutyryl chloride in Example 61 C. The 30 crude product was purified by trituration with 1 :1 diethyl ether-hexane. The resulting solid was dissolved in CH3CN and water and lyophilized to give the product as a white solid. 1 H NMR (CDCI3, 300 MHz) mixture of rotamers δ 0.80 (t, J=8Hz) and 1.05 (t, J=8Hz) and 1.20 (m) and 1.42 (m) total of 8H for the four peaks, 2.35 (br s, 1 H), 2.70 (m, 1 H), 3.0 (m, 3H), 35 3.2 (m, 3H), 3.25 (dq, 1 H, J=1 ,8Hz), 3.42 (m, 1 H), 3.6 (m, 1H), 3.75 (m, 1H), 3.78 (s, 3H), 4.8 (br s, 1H), 5.95 (s, 2H), 6.74 (d, 1 H, J=8Hz), 6.85 (m, 3H), 7.00 (s, 1 H), 7.30 (d, 2H, J=8Hz). MS (DCI/NH3) m/e 498 (M+H) + . Anal calcd for C-27H35N3O6 • 0.75 H 0: C, 63.45; H, 7.20; N, 8.22. Found: C, 63.38; H, 7.29; N, 8.44. Example 98 frans. frans-2-4-Methoxv p henvn-4- .3- benzodioxol-5-vl - 1-r2-fN-butyl-N- butyrylaminotethvllpvrrolidine-3-carboxylic acid The title compound was prepared by the methods described in Example 61 , but substituting butylamine for methylamine in Example 61 B and butyryl chloride for isobutyryl chloride in Example 61 C. The crude product was purified by trituration with 1 :1 diethyl ether-hexane. The resulting solid was dissolved in CH3CN and water and lyophilized to give the product as a white solid. 1 H NMR (CDCI3, 300 MHz) δ 0.80 (m, 3H), 0.90 (t, 3H, J=8Hz), 1.45 (m, 4H), 1.6 (m, 2H), 2.20 (t, 3H, J=8Hz), 2.94 (br m, 2H), 3.10 (br m, 2H), 3.5 (br m, 4H), 3.80 (br m, 2H), 3.82 (s, 3H), 4.30 (br s, 1 H), 5.95 (s, 2H), 6.75 (d, 1 H, J=8Hz), 6.84 (m, 1 H), 6.85 (d, 2H, J=8Hz), 7.04 (d, 1 H, J=1Hz), 7.40 (d, 2H, J=8Hz). MS (DCI/NH3) m/e 511 (M+H)+. HRMS calcd for C29H38N2O6: 511.2808. Found: 51 1 .2809 Example 99 frans.frans-2-(4-Methoxy p henvn-4-f1.3-benz p dioxol-5-vn-1-[2-fN-propyl-N- ethoxvcarbonvlamino ethvnpvrrolidine-3-carboxvlic acid The title compound was prepared by the methods described in Example 61 , but substituting propylamine for methylamine in Example 61 B and ethyl chloroformate for isobutyryl chloride in Example 61 C. The crude product was purified by trituration with 1 :1 diethyl ether- hexane. The resulting solid was dissolved in CH3CN and water and lyophilized to give the product as a white solid. 1 H NMR (CDCI3, 300 MHz) δ 0.80 (t, 3H, J=8Hz), 1.05 (m, 2H), 1.22 (m, 3H), 1.45 (m. 3H), 2.08 (br s, 1 H), 2.75 (m, 1 H), 2.88 (br q, 2H, J=8Hz), 3.08 (br m, 2H), 3.27 (br m, 2H), 3.44 (m, 1 H), 3.54 (dt, 1H, J=1 ,8Hz), 3.63 (d, 1 H, J=8Hz), 3.78 (s, 3H), 4.02 (br d, 2H), 5.93 (s, 2H), 6.72 (d, 1 H, J=8Hz), 6.81 (dd, 1 H, J=1,8Hz), 6.85 (d, 2H, J=8Hz), 7.00 (s, 1 H), 7.30 (d, 2H, J=8Hz). MS (DCI/NH3) m/e 499 (M+H)+. Anal calcd for C27H34N2O7 • 0.5 H 2 0: C, 63.89; H, 6.95; N, 5.52. Found: C, 64.03; H, 6.71 ; N, 5.30. Examole 100 frans.frans-2-f4-Methoxyphenvn-4-(1.3-benzodioxol-5-vh-1-[2-t , N-methyl-N-f2- ethylbutvrvnamino)ethyπpyrrolidine-3-carboxylic acid To the compound resulting from Example 61 B (190 mg) dissolved 5 in THF (2 mL) was added HOBt (60 mg), EDCI (85 mg), N- methylmorpholine (50 μL), and DMF (2 mL). 2-Ethylbutyric acid was added and the solution stirred overnight at ambient temperature. Water (10 mL) was added, and the mixture was extracted with EtOAc (2 x 25 mL). The combined organic extracts were washed with saturated ι o sodium bicarbonate solution, 1 N. H3PO4, and brine, dried with Na2Sθ4, and evaporated to give an oil which was purified by flash chromatography on silica gel eluting with 1 :3 EtOAc-hexane. The resulting ethyl ester was saponified by the procedure described in Example 61 C. The crude product was dissolved in CH3CN and water and 15 lyophilized to give the product as a white solid. 1 H NMR (CDCI3, 300 MHz) (mixture of rotamers) δ 0.66, 0.74, 0.80, 0.88 (all triplets, total of 6H, J=8Hz), 1.05 (m, 2H), 1.25-1.75 (m, 5H), 2.16 (m, 1 H), 2.32 (m, 1H), 2.45 (m, 1H), 2.70 (m, 1 H), 2.86, 2.94 (s, total 3H), 2.95 (m, 1H), 3.35 (m, 1 H), 3.52 (m, 2H), 3.65 (m, 1 H), 3.80 (s, 3H), 5.g4, 5.96 (s, total 2H), 20 6.73 (m, 1H), 6.84 (m, 3H), 6.97 (m, 1 H), 7.30 (m, 2H). MS (DCI/NH 3 ) m/e 497 (M+H)+. Anal calcd for C2 8 H3 6 N2O6 - 0.25 H 2 0: C, 67.11 ; H, 7.34; N, 5.59. Found: C, 67.13; H, 7.24; N, 5.56. Example 1Q1 2 5 frans.frans-2-f4-MethoxyphenylV4-M.3-benzodioxol-5-vn-1-f2-fN-methyl-N-f2- propylvalerynaminotethyllpyrrolidine-3-carboxylic acid The title compound was prepared by the procedure described in Example 100, but substituting 2-propylpentanoic acid for 2- ethylbutyric acid. The crude product was purified by preparative HPLC 30 (Vydac μC18) eluting with a 10-70% gradient of CH3CN in 0.1% TFA. The desired fractions were lyophilized to give the product as a white solid. 1 H NMR (CDCI 3 . 300 MHz) δ 0.79 (t, 3H, J=8Hz), 0.82 (t, 3H, J=8Hz), 1.10 (m, 4H), 1.2-1.5 (m, 4H), 2.55 (m, 1H), 2.96 (s, 3H), 3.15 (br m, 1H), 3.32 (br m, 1H), 3.56 (m, 2H), 3.68 (m, 1H) 3.68 (s, 3H), 3.70 (m, 1H), 3.80 ( , 35 2H), 4.65 (br d, 1 H), 5.92 (s, 2H), 6.75 (d, 1 H, J=8Hz), 6.84 (m, 1H), 6.85 (d, 2H, J=8Hz), 7.05 (s, 1H), 7.42 (d, 2H, J=8Hz). MS (DCI/NH3) m e 525 (M+H) + . Anal calcd for C 3 0H 4 0N2O6 ■ 1.25 TFA: C, 58.51 ; H, 6.23; N, 4.20. Found: C, 58.52; H, 6.28; N, 4.33. Example 102 frans.frans-2- 4-Methoxyphenyn-4-(1.3-benzodioxol-5-vn-1-r2-fN-propyl-N-ftert- butyloxycarboπylmethv0aminotethyl]pyrrolidine-3-carboxylic acid The title compound was prepared by the methods described in Example 61 , but substituting propylamine for methylamine in Example 61 B and t-butyl bromoacetate for isobutyryl chloride in Example 61 C. The crude product was purified by trituration with 1 :1 diethyl ether- hexane. The resulting solid was dissolved in CH3CN and water and lyophilized to give the product as a white solid. 1 H NMR (CDCI3. 300 MHz) δ 0.82 (t, 3H, J=8Hz), 1.18 (m, 2H), 1.19 (s, 9H), 2.12 (m, 1H), 2.46 (m, 2H), 2.70 (m, 3H), 2.85 (m, 2H), 3.20 (s, 2H), 3.40 (dd, 1H, J=2,8Hz), 3.50 (dt, 1 H, J=2,8Hz), 3.62 (d, 1 H, J=8Hz), 3.78 (s, 3H), 5.95 (s, 2H), 6.72 (d, 1H, J=8Hz), 6.84 (m, 1H), 6.85 (d, 2H, J=8Hz), 7.05 (s, 1H), 7.16 (d, 2H, J=8Hz). MS (DCI/NH3) m/e 541 (M+H)+. Anal calcd for C30H40N2O7 LO H 2 0: C, 64.50; H, 7.58; N, 5.01. Found: C, 64.75; H, 7.35; N, 4.86. Example 103 frans.frans-2-f4-Methoxyphenvn-4-f1.3-benzodioxol-5-yn-1-[2-fN-propyl-N-fn- propylaminocarbonylmethvhamino^ethvnpyrrolidine-3-carboxylic acid The title compound was prepared by the methods described in Example 61 , but substituting propylamine for methylamine in Example 61 B and N-propyl bromoacetamide for isobutyryl chloride in Example 61 C. The crude product was purified by preparative HPLC (Vydac μC18) eluting with a 10-70% gradient of CH3CN in 0.1% TFA. The desired fractions were lyophilized to give the product as a white solid. 1 H NMR (CDCI3, 300 MHz) δ 0.78 (t, 3H, J=8Hz), 0.88 (t, 3H, J=8Hz), 1.45 (m, 2H), 1.48 (m, 3H, J=8Hz), 2.55-2.7 (m, 2H), 2.90 (m, 1 H), 3.04 (m, 1H), 3.15 (m, 3H), 3.28 (t, 1H, J=8Hz), 3.45 (t, 1H, J=8Hz), 3.60 (m, 2H), 3.70 (d, 2H, J=8Hz), 3.75 (m, 1 H), 3.80 (s, 3H), 4.25 (d, 1H, J=8Hz), 5. 5 (s, 2H), 6.75(d, 1H, J=8Hz), 6.86 (dt, 1H, J=1 ,8Hz), 6.88 (d, 2H, J=8Hz), 7.04 (d, 1H, J=1 Hz), 7.40 (d, 2H, J=8Hz). MS (DCI/NH3) m/e 526 (M+H)+. Anal calcd for C29H3 9 N3O6 1.85 TFA: C, 53.32; H, 5.59; N, 5.70. Found: C, 53.45; H, 5.62; N, 5.63. Examole 104 frans.frans-2-f4-Methoxv p henvn-4- ( 1.3-benzodioxol-5-vh-1-f2-N-propyl-N-f4- methoxyphenoxycarbonvnamino ethyl]pyrrolidine-3-carboxylic acid The title compound was prepared by the methods described in Example 61 , but substituting propylamine for methylamine in Example 61 B and 4-methoxyphenylchloroformate for isobutyryl chloride in Example 61 C. The crude product was purified by trituration with 1 :1 diethyl ether-hexane. The resulting solid was dissolved in CH3CN and water and lyophilized to give the product as a white solid. 1 H NMR (CD3OD, 300 MHz) mixture of rotamers δ 0.88 (m,3H), 1.57 (m, 2H), 2.45 (br s) and 2.60 (br s, total of 1 H), 2.90-3.15 (m, 4H), 3.42-3.7 (m, 5H), 3.78 (s, 3H), 3.80 (s, 3H), 3.85 (m) and 4.0 (m, total of 1 H), 5.95 (s) and 5.98 (s, total of 2H), 6.63(m, 1 H), 6.72 (d, 1 H, J=8Hz), 6.81 (m, 2H), 6.93 (m, 5H), 7.40 (m, 2H). MS (DCI/NH3) m/e 577 (M+H) + . Anal calcd for C32H36N2O8 • 1.0 H 2 O: C, 64.63; H, 6.44; N, 4.71. Found: C, 64.70; H, 6.38; N, 4.63. Example 105 frans.frans-2-(4-Methoxyphenyn-4-M .3-benzodioxol-5-yn-1-r2-ι , N-propvl-N-f4- methoxvbenzovlteminotethvnpvrrolidine-3-carboxvlic acid The title compound was prepared by the methods described in Example 61 , but substituting propylamine for methylamine in Example 61 B and anisoyl chloride for isobutyryl chloride in Example 61C. The crude product was purified by trituration with 1 :1 diethyl ether-hexane. The resulting solid was dissolved in CH3CN and water and lyophilized to give the product as a white solid. 1 H NMR (CDCI3, 300 MHz) mixture of rotamers δ 0.78 (m) and 0.98 (t, J=8Hz) total of 3H, 1.47 (m) and 1.52 (q, J=8Hz) total of 2H, 2.25 (br s, 1H), 2.78 (br s, 1 H), 2.90 (br t, 2H), 3.12- 3.68 (m, 7H), 3.80 (s, 3H), 3.82 (s, 3H), 5.94 (s, 2H), 6.75(d, 1 H, J=8Hz), 6.83 (m, 5H), 6.94 (m, 1 H), 7.22 (m, 4H). MS (FAB) m/e 561 (M+H) + . Anal calcd for C32H36N2O7 • 0.75 H 2 0: C, 66.94; H, 6.58; N, 4.88. Found: C, 67.00; H, 6.38; N, 4.59. Example 106 frans. frans-2-f4-Methoxyphenvn-4-M .3-benzodioxol-5-yl)-1-f2-fN-propyl-N- benzovlamino ethyllpyrrolidine-3-carboxylic acid The title compound was prepared by the methods described in Example 61 , but substituting propylamine for methylamine in Example 61 B and benzoyl chloride for isobutyryl chloride in Example 61C. The crude product was purified by trituration with 1 :1 diethyl ether-hexane. The resulting solid was dissolved in CH3CN and water and lyophilized to give the product as a white solid. 1 H NMR (CDCI3, 300 MHz) mixture of rotamers δ 0.65 and 0.9 (m, total of 3H) , 1.4 and 1.55 (m, total of 2H), 2.05 and 2.15 (m, total of 1 H), 2.6 - 3.6 (m, 8H), 5.92 (s, 2H), 6.70(d, 1H, J=8Hz), 6.82 (m, 4H), 7.2 - 7.4 (m, 6H). MS (DCI/NH3) m/e 531 (M+H)+. Anal calcd for C 31 H3 4 N2O6 • 0.3 H 2 0: C, 69.46; H, 6.51 ; N, 5.23. Found: C, 69.48; H, 6.19; N, 4.84. Example 107 fraπs.frans-2-f4-Methoxyphenvn-4-ι , 1.3-benzodioxol-5-vlV1-[2-rN-propyl-N- beπzyloxycarbonylaminotethy pyrrolidine-3-carboxylic acid The title compound was prepared by the methods described in Example 61 , but substituting propylamine for methylamine in Example 61 B and benzyl chloroformate for isobutyryl chloride in Example 61 C. The crude product was purified by preparative HPLC (Vydac μC18) eluting with a 10-70% gradient of CH3CN in 0.1% TFA. The desired fractions were lyophilized to give the product as a white solid. 1 H NMR (CDCI3, 300 MHz) δ 0.8 (m, 3H) 1.45 (m, 2H), 2.20 (br m, 1H), 2.75 (m, 1 H), 2.93 (m, 1 H), 3.15 (m, 2H), 3.32 (m, 3H), 3.52 (m, 2H), 3.66 (m, 1 H), 3.78 (s, 3H), 5.00 (m, 2H), 5.94 (s, 2H), 6.72(d, 1 H, J=8Hz), 6.82 (m, 3H); 7.0 (br d, 1 H, J= 15Hz), 7.2 (s, 4H), 7.30 (m, 3H). MS (FAB) m/e 561 (M+H) + . Anal calcd for C32H36N2O7 • 1.0 TFA: C, 60.53; H, 5.53; N, 4.15. Found: C, 60.66; H, 5.34; N, 4.28. Example 1Q8 frans.frans-2- ( 4-Methoxy p henyn-4-M .3-benzodioxol-5-vn-1-[2-fN-propyl-N- - methQxybenzvloxvcarbonvnamino)ethvllpyrrolidine-3-carboxylic acid The title compound is prepared by the methods described in Example 61 , substituting propylamine for methylamine in Example 61 B and 4-methoxybenzyl chloroformate for isobutyryl chloride in Example 61C. Example 109 5 frans.frans-2-f4-Methoxvphenvn-4-f1.3-benzodioxol-5-vn-1-r2-. / N-butvl-N- ethoxvcarbonvlaminotethvllpvrrolidine-3-carboxylic acid The title compound was prepared by the methods described in Example 61 , but substituting butylamine for methylamine in Example 61 B and ethyl chloroformate for isobutyryl chloride in Example 61C. ι o The crude product was purified by preparative HPLC (Vydac μC18) eluting with a 10-70% gradient of CH 3 CN in 0.1% TFA. The desired fractions were lyophilized to give the product as a white solid. 1 H NMR (CDCI 3 , 300 MHz) δ 0.82 (t, 3H, J=8Hz), 1.20 (m, 5H), 1.34 (m, 2H), 3.08 (m, 2H), 3.17 (m, 2H), 3.52 (m, 2H), 3.75 (m, 2H), 3.78 (s, 3H), 4.06 (q, 15 2H, J=8Hz), 4.35 (br s, 1H), 5.94 (s, 2H), 6.76 (d, 1 H, J=8Hz), 6.92 (d, 2H, J=8Hz), 7.03 (br s, 1H), 7.17 (br s, 1H), 7.7 (br s, 2H). MS (FAB) m/e 513 (M+H)+. Anal calcd for C28H36N2O7 • 0.5 TFA: C, 61.15; H, 6.46; N, 4.92. Found: C, 60.99; H, 6.80; N, 4.93. 20 Example 110 frans.frans-2- 4-Methoxyphenvn-4-n .3-benzodioxol-5-vn-1-f2-ι , N-butvl-N- propoxycarbonylaminotethvnpyrrolidine-3-carboxylic acid The title compound was prepared by the methods described in Example 61 , but substituting butylamine for methylamine in Example 25 61 B and propyl chloroformate for isobutyryl chloride in Example 61C. The crude product was purified by trituration with 1 :1 diethyl ether- hexane. The resulting solid was dissolved in CH3CN and water and lyophilized to give the product as a white solid. 1 H NMR (CDCI3, 300 MHz) δ 0.80 (br s, 1H), 0.85 (t, 3H, J=8Hz), 0.92 (br s, 1H), 1.22 (m, 3H), 30 1.40 (m, 3H), 1.62 (br m, 1 H), 2.15 (br s, 1 H), 2.72 (m, 1 H), 2.87 (m, 1H), 3.1-3.45 (m, 5H), 3.55 (m, 1 H), 3.64 (d, 1 H, J=8Hz), 3.79 (s, 3H), 3.88 (br s, 1H), 3.97 (br s, 1 H), 5.95 (s, 2H), 6.73(d, 1 H, J=8Hz), 6.85 (m, 3H, 7.0 (s, 1H), 7.30 (d, 2H, J=8Hz). MS (FAB) m/e 527 (M+H) + . Anal calcd for C29H38N2O7 ■ 0.15 H 2 0: C, 65.80; H, 7.29; N, 5.29. Found: C, 65.79; H, 35 7.30; N, 5.21. Example 111 frans.frans-2-f4-Methoxyphenyn-4-f1.3-benzodioxol-5-yn-1-[2-rN-propyl-N- propoxycarbonvlaminotethyl)pvrrolidine-3-carboxylic acid The title compound was prepared by the methods described in Example 61 , but substituting propylamine for methylamine in Example 61 B and propyl chloroformate for isobutyryl chloride in Example 61 C. The crude product was purified by trituration with 1 :1 diethyl ether- hexane. The resulting solid was dissolved in CH 3 CN and water and lyophilized to give the product as a white solid. 1 H NMR (CDCI3, 300 MHz) δ 0.80 (t, 3H, J=8Hz), 093 (m, 3H), 1.43 (m, 3H), 1.62 (m, 1H), 2.15 (br s, 1H), 2.68-3.45 (m, 8H), 3.54 (m, 1H), 3.66 (m, 1 H), 3.78 (s, 3H), 3.94 (m, 2H), 5.94 (s, 2H), 6.72 (d, 1H, J=8Hz), 6.82 (m, 1 H), 6.84 (d, 2H, J=8Hz), 7.00 (br s, 1H), 7.33 (m, 2H). MS (DCI/NH 3 ) m/e 513 (M+H) + . Anal calcd for C28H36N2O7 0.15 H 2 0: C, 65.26; H, 7.10; N, 5.44. Found: C, 65.22; H, 6.74; N, 5.06. Example 112 frans.frans-1-fN.N-Difn-butyhaminocarbonvnmethvl-2.4-di(1.3-benzodioxol-5- vnpvrrolidine-3-carboxylic acid Ethyl (3,4-methylenedioxybenzoyl)acetate, prepared by the method of Krapcho et al., Org. Syn. 4_7, 20 (1967) starting with 3,4- methylenedioxyacetophenone instead of 4-methoxyacetophenone, was reacted by the procedures described in Example 1 to give the title compound as a white solid, m.p. 58-60 °C. 1 H NMR (CDCI 3 , 300 MHz) δ 0.87 (quintet, J=6Hz, 6H), 1.12 (sextet, J=6Hz, 2H), 1.24-1.51 (m, 6H), 2.80 (d, J=13Hz, 1H), 2.94-3.12 (m, 4H), 3.28-3.50 (m, 4H), 3.58-3.62 (m, 1H), 3.78 (d, J=9Hz, 1H), 5.95 (s, 4H), 6.73 (dd, J=8Hz, 3Hz, 2H), 6.84-6.89 (m, 2H), 6.92 (d, J=1Hz, 1H), 7.01 (d, H=1Hz, 1 H). MS (DCI/NH3) m/e 525 (M+H) + . Example 113 frans.frans-1-f2-fN-fn-Butvn-N-propvlsulfonvlamino^ethyn-2-f4-methoxyphenyn-4- ( 1.3-benzodioxol-5-vhPvrrolidine-3-carboxylic acid Using the procedures described in Example 66, the title compound was prepared as a white solid, m.p. 64-65 °C. 1 H NMR (CDCI 3 , 300 MHz) δ 0.83 (t, J=7Hz, 3H), 0.98 (t, J=7Hz, 3H), 1.12-1.25 (m, 2H), 1.32-1.41 (m, 2H), 1.75 (sextet, J=7Hz, 2H), 2.23-2.31 (m, 2H), 2.72-3.32 (m, 8H), 3.43 (dd, J=9Hz, 3Hz, 1H), 3.53-3.59 (m, 1H), 3.65 (d, J=9Hz, 1 H), 3.80 (s, 3H), 5.95 (s, 2H), 6.73 (d, J=8Hz, 1 H), 6.83 (dd, J=8Hz, 1 Hz, 1 H), 6.88 (d, J=9Hz, 2H), 7.02 (d, J=1 Hz, 1 H), 7.33 (d, J=9Hz, 2H). MS (DCI/NH3) m/e 547 (M+H) + . Example 114 frans.frans-l-fN.N-Difn-butvnaminocarbonvlmethvn^- -methQxvnhenvn^-n .a- benzodioxol-5-vnpvrrolidine-3-carboxvlic acid Using the procedures described in Examples 28 and 43, the title compound was prepared as a white solid, m.p. 74-76 °C. 1 H NMR (CDCI3. 300 MHz) δ 0.80 (t, J=6Hz, 3H), 0.88 (t, J=8Hz, 3H), 1.08 (sextet, J=8Hz, 2H), 1.21-1.48 (m, 6H), 2.75 (d, J=12Hz, 1 H), 2.95-3.09 (m, 4H), 3.26-3.59 (m, 5H), 3.75 (d, J=9Hz, 1 H), 3.79 (s, 3H), 4.28 (s, 4H), 6.78 (d, J=9Hz, 1H), 6.85 (d, J=9Hz, 2H), 6.91 (d,d, J=3Hz, 9Hz, 1 H), 6.98 (d, J=3Hz, 1 H), 7.32 (d, J=9Hz, 2H). MS (DCI/NH3) m/e 525 (M+H) + . Example 115 frans.frans-1-(2-fN-Propyl-N-propylsulfonylamino ethvπ-2- ( 4-methoxyphenvπ-4- .1.3-benzodioxol-5-vπpyrrolidine-3-carboxylic acid Using the procedures described in Example 66, the title compound was prepared as a white solid, m.p. 72-73 °C. 1 H NMR (CDCI3, 300 MHz) δ 0.79 (t, J=8Hz, 3H), 0.98 (t, J=8Hz, 3H), 1.43 (sextet, J=8Hz, 2H), 1.75 (sextet, J=8Hz, 2H), 2.22-2.32 (m, 1 H), 2.69-3.32 (m, 9H), 3.42 (dd, J=3Hz, 12Hz, 1 H), 3.52-3.58 (m, 1H), 3.64 (d, J=12Hz, 1 H), 3.80 (s, 3H), 5.95 (s, 2H), 6.73 (d, J=11Hz, 1H), 6.83 (dd, J=1 Hz, 11 Hz, 1H), 6.87 (d, J=11 Hz, 2H), 7.0 (d, J=2Hz, 1 H), 7.32 (d, J=11Hz, 2H). MS (DCI/NH3) m/e 533 (M+H) + . Example 116 frans.frans-1-f2-fN-Butyl-N-butylsulfonylamino)ethvh-2-(4-methoxyphenvh-4- .3- benzodioxor-5-yπpyrrolidine-3-carboxylic acid Using the procedures described in Example 66, the title compound was prepared as a white solid, m.p. 62-63 °C. 1 H NMR (CDCI3, 300 MHz) δ 0.82 (t, J=6Hz, 3H), 0.91 )t, J=6Hz, 3H), 1.20 (sextet, J=6Hz, 2H), 1.33- 1.42 (m, 4H), 1.68 (quintet, J=6Hz, 3H),2.23-2.32 (m, 1 H), 2.70-3.28 (m, 9H), 3.41 (d, J=8Hz, 1 H), 3.52-3.58 (m, 1 H), 3.65 (d, J=8Hz, 1H), 3.79 (s, 3H), 5.95 (s, 2H), 6.72 (d, J=8Hz, 1 H), 6.82 (d, J=8Hz, 1 H), 6.87 (d, J=8Hz, 2H), 7.01 (s, 1 H), 7.32 (d, J=8Hz, 2H). MS (DCI/NH3) m/e 561 (M+H) + . Example 117 frans.frans-1-ι2-fN.N-Dibutylaminocarbonvlmethvn-2-f4-methoxymethoxyphenyn- 4-M .3-benzodioxol-5-vnpvrrolidine-3-carboxylic acid 4-Hydroxyacetophenone was treated with chloromethyl methyl ether and triethylamine in THF at room temperature to give ethyl 4- methoxymethoxybenzoylacetate which was treated by the procedures described in Example 1 to afford the title compound as a white solid, m.p. 48-49 °C. 1 H NMR (CDCI3, 300 MHz) δ 0.81 (t, J=7Hz, 3H), 0.88 (t, J=7Hz, 3H), 1.06 (sextet, J=7Hz, 2H), 1.20-1.35 (m, 4H), 1.44 (quintet, J=7Hz, 2H), 2.75 (d, J=12Hz, 1 H), 2.94-3.10 (m, 4H), 3.25-3.35 (m, 1H), 3.40 (d, J=12Hz, 1 H), 3.43-3.52 (m, 2H), 3.47 (s, 3H), 3.55-3.62 (m, 1 H), 3.77 (d, J=9Hz, 1H), 5.15 (s, 2H), 5.g4 (m, 2H), 6.73 (d, J=8Hz, 1 H), 6.86 (dd, J=1 Hz, 8Hz, 1H), 7.0 (d, J=8Hz, 2H), 7.04 (d, J=1 Hz, 1 H), 7.32 (d, J=8Hz, 2H). MS (DCI/NH3) m/e 541 (M+H) + . Example 118 frans.frans-1-f2-(N.N-Dibutylaminocarbonylmethvπ-2-f4-hydroχyphenyn-4-f1.3- benzodioxol-5-vflpyrrolidine-3-carboxylic acid hydrochloride salt The compound resulting from Example 116 was treated with concentrated HCl in 1 :1 THF-isopropanol to give the title compound as a white solid, m.p. 211-212 °C. H NMR (CD3OD, 300 MHz) δ 0.90 (t, J=8Hz, 6H), 1.12-1.27 (m, 6H), 1.36-1.45 (m, 2H), 3.04 (bs, 1 H), 3.14- 3.35 (t, J=9Hz, 1H), 3.90 (bs, 3H), 4.17 (d, J=15Hz, 1 H), 5.96 (S, 2H), 6.82-6.93 (m, 4H), 7.03 (d, J=1 Hz, 1 H), 7.42 (bs, 2H). MS (DCI/NH3) m/e 497 (M+H) + . Example 119 frans.frans-1-(2-(N-lsobutyl-N- p ro p ylsulfonylamino ) ethylV2-f4-methoxyphenyπ-4- ( 1.3-benzodioxol-5-vπpyrrolidine-3-carboxylic acid Using the procedures described in Example 66, the title compound was prepared as a white solid, m.p. 73-74 °C. 1 H NMR (CDCI3, 300 MHz) δ 0.80 (d, J=6Hz, 6H), 0.98 (t, J=8Hz, 3H), 1.62 (sextet, J=6Hz, 1 H), 1.74 (sextet, J=8Hz, 2H), 2.23-2.34 (m, 1 H), 2.68-2.98 (m, 7H), 3.08-3.18 (m, 1 H), 3.26-3.42 (m, 2H), 3.52-3.58 (m, 1 H), 3.65 (d, J=9Hz, 1 H), 3.80 (s, 3H), 5.90 (s, 2H), 6.74 (d, J=8Hz, 1 H), 6.82 (d, J=8Hz, 1H), 6.86 (d, J=8Hz, 2H), 6.98 (d, J=1 Hz, 1 H), 7.33 (d, J=8Hz, 2H). MS (DCI/NH3) m/e 547 (M+H) + . Example 120 frans.frans-1-r2-fN-Benzenesulfonvl-N- p ropvlamino ) ethvh-2-f4-methoxyphenvn-4- (1.3-benzodioxol-5-vnpvrrolidine-3-carboxylic acid Using the procedures described in Example 66, the title compound was prepared as a white solid, m.p. 89-91 °C. 1 H NMR (CDCI3, 300 MHz) δ 0.74 (t, J=6Hz, 3H), 1.33 (sextet, J=6Hz, 2H), 2.20-2.30 (m, 1 H), 2.62- 2.72 (m, 1H), 2.85-3.05 (m, 4H), 3.12-3.22 (m, 1H), 3.38 (dd, J=3Hz, 9Hz, 1 H), 3.49-3.57 (m, 1 H), 3.62 (d, J=9Hz, 1 H), 3.82 (s, 3H), 5.g6 (s, 2H), 6.73 (d, J=8Hz, 1H), 6.84 (dd, J=1Hz, 8Hz, 1H), 6.85 (d, J=9Hz, 2H), 7.02 (d, J=1Hz, 1 H), 7.28 (d, J=9Hz, 2H), 7.39-7.54 (m, 3H), 7.70 (d, J=7Hz, 2H). MS (DCI/NH3) m/e 567 (M+H) + . Example 121 frans.frans-1-f2-fN-f4-Methoxybenzenesulfonvn-N-propvlamino^ethvh-2-(4- methoxyphenvn-4-f1.3-benzodioxol-5-vnpvrrolidine-3-carboxvlic acid Using the procedures described in Example 66, the title compound was prepared as a white solid, m.p. 96-g7 °C. 1 H NMR (CDCI3, 300 MHz) δ 0.73 (t, J=7Hz, 3H), 1.34 (sextet, J=7Hz, 2H), 2.20-2.30 (m, 1 H), 2.62- 2.71 (m, 1 H), 2.82-3.03 (m, 4H), 3.08-3.18 (m, 2H), 3.38 (dd, J=3Hz, 9Hz, 1 H), 3.48-3.56 (m, 1 H), 3.62 (d, J=9Hz, 1 H), 3.81 (s, 3H), 3.86 (s, 3H), 5.95 (S, 2H), 6.73 (d, J=8Hz, 1 H), 6.81-6.89 (m, 5H), 7.01 (d, J=1 Hz, 1 H), 7.28 (d, J=8Hz, 2H), 7.62 (d, J=8Hz, 2H). MS (DCI/NH3) m/e 597 (M+H) + ._ Example 122 frans.frans-1-(N. N-Dim-butvnaminocarbonylmethvπ-2-f2-methoxyethoxy-4- methoxyphenvπ-4-(1.3-benzodioxol-5-vπpyrrolidine-3-carboxylic acid 2-Hydroxy-5-methoxyacetophenone was treated with sodium hydride and bromoethyl methyl ether in THF at 70 °C to provide ethyl 2-methoxyethoxy-4-methoxybenzoylacetate which was treated by the procedures described in Example 1 to provide the title compound as a white solid, m.p. 63-65 °C. 1 H NMR (CDCI3, 300 MHz) δ 0.84 (t, J=7Hz, 3H), 0.89 (t, J=7Hz, 3H), 1.16 (sextet, J=7Hz, 2H), 1.28 (sextet, J=7Hz, 2H), 1.45-1.52 (m, 4H), 2.87-2.94 (m, 2H), 3.00-3.16 (m, 3H), 3.26-3.36 (m, 2H), 3.43 (s, 3H), 3.47-3.54 (m, 3H), 3.66-3.72 (m, 2H), 3.78 (s, 3H), 3.76-3.84 (m, 1 H), 4.02-4.10 (m, 2H), 4.25 (d, J=9Hz, 1 H), 5.92 (s, 2H), 6.40 (d, J=2Hz, 1 H), 6.52 (dd, J=2Hz, 9Hz, 1 H), 6.70 (d, J=8Hz, 1 H), 6.83 (dd, J=1Hz, 8Hz, 1 H), 5.98 (d, J=2Hz, 1 H), 7.53 (d, J=9Hz, 1 H). MS (DCI/NH3) m/e 585 (M+H) + . Example 123 frans frans-1-f2-(N-Pro p vl-N-r2.4-dimethvlbenzenesulfonvnamino)ethvn-2- 4- methoxyphenvh-4-π .3-benzodioxol-5-vhpvrrolidine-3-carboxylic acid Using the procedures described in Example 66, the title compound was prepared as a white solid, m.p. 88-90 °C. 1 H NMR (CDCI3, 300 MHz) δ 0.69 (t, J=7Hz, 3H), 1.32 (sextet, J=7Hz, 2H), 2.12-2.20 (m, 1 H), 2.32 (s, 3H), 2.47 (s, 3H), 2.62-2.69 (m, 1 H), 2.78 (t, J=9Hz, 1H), 2.89 (dd, J=8Hz, 1 H), 3.02 (sextet, J=9Hz, 2H), 3.15-3.32 (m, 3H), 3.46-3.55 (m, 1 H), 3.60 (d, J=9Hz, 1 H), 3.82 (s, 3H), 5.96 (s, 2H), 6.72 (d, J=7Hz, 1 H), 6.80 (dd, J=1 Hz, 9Hz, 1H), 6.86 (d, J=9Hz, 2H), 6.97 (d, J=1 Hz, 1 H), 7.03 (bs, 2H), 7.29 (d, J=9Hz, 1 H). MS (DCI/NH3) m/e 5 5 (M+H) + . Example 124 frans.frans-1-f2-fN-Propyl-N-(3-chloropropylsulfonv amino'>ethyl'>-2-(4- methoxyphenvπ-4-f1.3-benzodioxol-5-vhpyrrolidine-3-carboxylic acid Using the procedures described in Example 66, the title compound was prepared as a white solid, m.p. 75-76 °C. 1 H NMR (CDCI3, 300 MHz) δ 0.80 (t, J=7Hz, 3H), 1.45 (sextet, J=7Hz, 2H), 2.15-2.31 (m, 3H), 2.70- 2.80 (m, 1 H), 2.85-3.10 (m, 6H), 3.23-3.31 (m, 2H), 3.43 (bd, J=9Hz, 1 H), 3.55-3.66 (m, 4H), 3.81 (s, 3H), 5.94 (s, 2H), 6.73 (d, J=8Hz, 1H), 6.82 (d, J=8Hz, 1H), 6.86 (d, J=8Hz, 2H), 7.00 (s, 1 H), 7.33 (d, J=8Hz, 2H). MS (DCI/NH3) m/e 567 (M+H) + . Example 125 frans. frans-1-(2-(N-Propyl-N-f2-methoxyethylsulfonyπamino)ethvh-2-f4- methoxyphenyl)-4-(1.3-benzodioxol-5-yhpyrrolidine-3-carboxylic acid Using the procedures described in Example 66, trans,trans-' -{2- (N-Propyl-N-(vinylsulfonyl)amino)ethyl)-2-(4-methoxyphenyl)-4-(1 ,3- benzodioxol-5-yl)pyrrolidine-3-carboxylic acid was prepared. Ester hydrolysis using aqueous sodium hydroxide in methanol afforded the title compound as a white solid, m.p. 62-64 °C. 1 H NMR (CDCI3, 300 MHz) δ 0.78 (t, J=7Hz, 3H), 1.42 (sextet, J=7Hz, 2H), 2.23-2.32 (m, 1 H), 2.72-2.79 (m, 1 H), 2.86-3.05 (m, 4H), 3.10-3.27 (m, 4H), 3.32 (s, 3H), 3.43 (dd, J=3Hz, 9Hz, 1H), 3.53-3.58 (m, 1 H), 3.65 (d, J=9Hz, 1 H), 3.6g (t, J=6Hz, 2H), 3.80 (s, 3H), 5.94 (s, 2H), 6.73 (d, J=8Hz, 1H), 6.82 (dd, J=1 Hz, 8Hz, 1 H), 6.87 (d, J=8Hz, 2H), 7.02 (d, J=1 Hz, 1 H), 7.33 (d, J=8Hz, 2H). MS (DCI/NH3) m/e 549 (M+H) + . Example 126 frans.frans-l-^-fN-Pro p yl-N-^-ethoxyethylsulfonvnamino^ethvn^- - meth pχ v p henyl -M .3-benzodioxol-5-vQ p yrrolidine-3-carboxylic acid Using the procedures described in Example 66, the title compound was prepared as a white solid, m.p. 58-60 °C. 1 H NMR (CDCI3, 300 MHz) δ 0.78 (t, J=7Hz, 3H), 1.18 (t, J=7Hz, 3H), 1.43 (sextet, J=7Hz, 2H), 2.24- 2.33 (m, 1 H), 2.70-2.80 (m, 1 H), 2.87-3.05 (m, 4H), 3.13-3.20 (m, 2H), 3.22-3.32 (m, 2H), 3.42 (dd, J=2Hz, 9Hz, 1H), 3.46 (q, J=7Hz, 2H), 3.52- 3.58 (m, 1 H), 3.65 (d J=9Hz, 1 H), 3.72 (t, J=6Hz, 2H), 3.80 (s, 3H), 5.95 (s, 2H), 6.73 (d, J=7Hz, 1 H), 6.83 (dd, J=1 Hz, 7Hz, 1 H), 6.87 (d, J=8Hz, 2H), 7.00 (d, J=1 Hz, 1 H), 7.32 (d, J=8Hz, 2H). MS (DCI/NH3) m/e 563 (M+H) + . Example 127 frans. frans-1-f 2-fN-Proρyl-N-(5-dimethylamino-1-naphthylsulfonvnamino)ethyn-2- (4-methoxyphenylV4-M .3-benzodioxol-5-yπpyrrolidine-3-carboxylic acid Using the procedures described in Example 66, the title compound was prepared as a yellow solid, m.p. 102-104 °C. 1 H NMR (CDCI3, 300 MHz) δ 0.62 (t, J=7Hz, 3H), 1.28 (sextet, J=7Hz, 2H), 2.12-2.20 (m, 1 H), 2.78 (t, J=9Hz, 1H), 2.88 (s, 6H), 2.72-2.89 (m, 1 H), 3.05-3.12 (m, 2H), 3.26-3.45 (m, 3H), 3.45-3.52 (m, 1 H), 3.58 (d, J=9Hz, 1 H), 6.97 (d, J=1 Hz, 1 H), 7.13 (d, J=7Hz, 1 H), 7.26 (d, J=8Hz, 1 H), 7.42-7.50 (m, 2H), 8.08 (dd, J=1 Hz, 7Hz, 1 H), 8.20 (d, J=8Hz, 1 H), 8.48 (d, J=8Hz, 1 H). MS (DCI/NH3) m/e 660 (M+H) + . Example 128 frans.frans-1-f2-fN-Propyl-N-fethylsulfonvnamino^ethvh-2-(4-methoxyphenyn-4- (1 ■3-benzodioxol-5-v pyrrolidine-3-carboxylic acid Using the procedures described in Example 66, the title compound was prepared as a white solid, m.p. 70-72 °C. 1 H NMR (CDCI3, 300 MHz) δ 0.79 (t, J=8Hz, 3H), 1.28 (t, J=7Hz, 3H), 1.43 (q, J=8Hz, 2H), 2.22-2.30 (m, 1 H), 2.71-2.80 (m, 1 H), 2.82-3.10 (m, 6H), 3.18-3.32 (m, 2H), 3.43 (dd, J=3Hz, 9Hz, 1 H), 3.53-3.60 (m, 1 H), 3.65 (d, J=9Hz, 1 H), 3.80 (s, 3H), 5.96 (s, 2H), 6.73 (d, J=7Hz, 1 H), 6.82 (dd, J=1 Hz, 7Hz, 1 H), 6.88 (d, s J=8Hz, 2H), 7.00 (d, J=1 Hz, 1 H),. 7.32 (d, J=8Hz, 2H). MS (DCI/NH3) m/e 519 (M+H) + . Example 129 frans. frans- 1-f2-fN-Propyl-N-f4-methylbenzenesulfonvπamino)ethvh-2-f 4- 0 methoxyphenvπ-4-f1.3-benzodioxol-5-vhPyrrolidine-3-carboxylic acid Using the procedures described in Example 66, the title compound was prepared as a white solid, m.p. 78-79 °C. 1 H NMR (CDCI3, 300 MHz) δ 0.73 (t, J=7Hz, 3H), 1.33 (sextet, J=7Hz, 2H), 2.20-2.30 (m, 1 H), 2.40 (s, 3H), 2.61-2.72 (m, 1 H), 2.83-3.05 (m, 4H), 3.08-3.19 (m, 2H), 3.48 5 (dd, J=3Hz, 9Hz, 1 H), 3.49-3.57 (m, 1 H), 3.62 (d, J=9Hz, 1 H), 3.81 (s, 3H), 5.95 (s, 2H), 6.73 (d, J=8Hz, 1 H), 6.82 (d, J=8Hz, 1 H), 6.87 (d, J=8Hz, 2H), 7.00 (s, 1 H), 7.21 (d, J=8Hz, 2H), 7.29 (d, J=8Hz, 2H), 7.57 (d, J=8Hz, 2H). MS (DCI/NH3) m/e 581 (M+H) + . 0 Example 130 frans.frans-1 -fN.N-Di(n-butyhaminocarbonylmethyπ-2-f3-pyridylV4-M .3- benzodioxol-5-yl)pyrrolidine-3-carboxylic acid Methyl nicotinoyl acetate was prepared by the method of Wenkert, et al., J. Org. Chem. 48: 5006 (1983) and treated by the procedures 5 described in Example 1 to provide the title compound as a white solid, m.p. 167-168 °C. 1 H NMR (CDCI3. 300 MHz) δ 0.82 (t, J-7Hz, 3H), 0.89 (t, J=7Hz, 3H), 1.14 (sextet, J=7Hz, 2H), 1.23-1.48 (m, 6H), 2.86-3.20 (m, 6H), 3.34-3.43 (m, 2H), 3.57 (dd, J=3Hz, 9Hz, 1 H), 3.75-3.83 (m, 1 H), 4.08 (d, J=9Hz, 1 H), 5.93 (s, 2H), 6.73 (d, J=8Hz, 1 H), 6.90 (dd, J=2Hz, 0 8Hz, 1 H), 7.03 (d, J=2Hz, 1 H), 7.38 (dd, J=4Hz, 8Hz, 1 H), 8.04 (d, J=8Hz, 1 H), 8.48 (dd, J=2Hz, 4Hz, 2H). MS (DCI/NH3) m/e 482 (M+H) + . Example 131 frans.frans-1-f2-fN-Propyl-N- ( n-butylsulfonvnamino^ethvn-2-f4-methoxyphenylV4- 5 (1.3-benzodioxol-5-vπpyrrolidine-3-carboxylic acid Using the procedures described in Example 66, the title compound was prepared as a white solid, m.p. 65-66 °C. 1 H NMR (CDCI3, 300 MHz) δ 0.78 (t, J=7Hz, 3H), 0.92 (t, J=7Hz, 3H), 1.31-1.46 (m, 4H), 1.68 (quintet, J=7Hz, 2H), 2.21-2.32 (m, 1 H), 2.70-3.08 (m, 7H), 3.12-3.23 (m, 2H), 3.42 (dd, J=2Hz, 9Hz, 1 H), 3.52-3.58 (m, 1 H), 3.64 (d, J=9Hz, 1 H), 3.80 (s, 3H), 5.96 (s, 2H), 6.72 (d, J=7Hz, 1H), 6.83 (dd, J=1 Hz, 7Hz, 1 H), 6.86 (d, J=8Hz, 2H), 7.00 (d, J=1Hz, 1 H), 7.32 (d, J=8Hz, 2H). MS (DCI/NH3) m/e 547 (M+H) + . Example 132 frans.frans-1 - ( 2- ( N-Pro p yl-N-(4-chlorobenzenesulfonvhamino^ethvh-2->f4- methoxyphenvπ-4-f1.3-benzodioxol-5-vhpyrrolidine-3-carboxylic acid Using the procedures described in Example 66, the title compound was prepared as a white solid, m.p. 105-106 °C. 1 H NMR (CDCI3, 300 MHz) δ 0.72 (t, J=7Hz, 3H), 1.34 (sextet, J=7Hzm 2H), 2.56-2.62 (m, 1 H), 2.78-2.86 (m, 1 H), 2.96-3.03 (m, 3H), 3.13-3.26 (m, 3H), 3.51 (dd, J=5Hz, 9Hz, 1 H), 3.62-3.68 (m, 1 H), 3.80 (s, 3H), 3.94 (d, J=9Hz, 1 H), 5.92 (s, 2H), 6.75 (d, J=8Hz, 1 H), 6.84 (dd, J=2Hz, 8Hz, 1 H), 6.g4 (d, J=8Hz, 2H), 6.98 (d, J=2Hz, 1 H), 7.36 (d, J=8Hz, 1 H), 7.49 (d, J=8Hz, 1H), 7.68 (d, J=8Hz, 1 H). MS (DCI/NH3) m/e 601 (M+H) + . Example 133 frans. frans- 1-f2-f N-Propvl-N-fbenzylsulfonvnamino^ethvn-2-f4-methoxvphenyn-4- (1.3-benzodioxol-5-yl)pyrrolidine-3-carboxylic acid Using the procedures described in Example 66, the title compound was prepared as a white solid, m.p. 88-89 °C. 1 H NMR (CDCI3, 300 MHz) δ 0.72 (t, J=7Hz, 3H), 1.32 (sextet, J=7Hz, 2H), 2.06-2.16 (m, 1 H), 2.56- 2.67 (m, 1 H), 2.75-3.10 (m, 6H), 3.30 (dd, J=2Hz, 9Hz, 1 H), 5.95 (s, 2H), 6.73 (d, J=7Hz, 1 H), 6.80 (dd, J=1 Hz, 7Hz, 1 H), 6.86 (d, J=8Hz, 2H), 6.97 (d, J=1 Hz, 1 H), 7.27-7.35 (m, 7H). MS (DCI/NH3) m/e 581 (M+H) + . Example 134 frans.frans-1-(2-(N-Propyl-N-f4-fluorobenzenesulfonyhamino)ethyh-2-(4- methoxyphenyn-4-(1.3-benzodioxol-5-vnpyrrolidine-3-carboxylic acid Using the procedures described in Example 66, the title compound was prepared as a white solid, m.p. 91-93 °C. 1 H NMR (CDCI3, 300 MHz) δ 0.73 (t, J=7Hz, 3H), 1.44 (sextet, J=7Hz, 2H), 2.18-2.27 (m, 1H), 2.56- 2.67 (m, 1 H), 2.78-2.87 (m, 2H), 2.97 (septet, J=8Hz, 2H), 3.11-3.16 (m, 2H), 3.33 (dd, J=2Hz, 9Hz, 1 H), 3.43-3.50 (m, 1 H), 3.57 (d, J=9Hz, 1 H), 3.78 (s, 3H), 7.08 (t, J=8Hz, 2H), 7.24 (d, J=8Hz, 2H), 7.69 (dd, J=5Hz, 8Hz, 2H). MS (DCI/NH3) m/e 585 (M+H) + . Example 135 frans.frans-1-fN-Methyl-N- p ro p ylaminocarbonylmethvπ-2-f4-methoxyphenylV4- 4- benzofuranvflpyrrolidine-3-carboxylic acid Example 135A Benzof u ran-4-carboxa Ideh vde To a suspension of 60% sodium hydride in mineral oil (4.00 g, 100 mmol, 1.25 eq) in DMF (60 mL) at 0 °C was added a solution of 3- bromophenol (13.8 g, 80 mmol) in DMF (5 mL). After 10 minutes, bromoacetaldehyde diethyl acetal (14.9 mL, 96.6 mmol, 1.24 eq) was added, and the resultant mixture then heated at 120 °C for 2.5 hours. The mixture was cooled to room temperature and was poured into water, and extracted once with ether. The organic solution was dried over MgS04, filtered, evaporated and vacuum distilled to yield a colorless liquid (17.1 g, 74%). b.p. 160-163 °C at 0.4 mm Hg. To warm polyphosphoric acid (15.3 g) was added a solution of the above compound (17.1 g, 59.3 mmol) in benzene (50 mL). The resultant mixture was heated under reflux with vigorous stirring for 4 hours, after which time the benzene layer was carefully decanted off, and the lower layer washed once with hexanes. The combined organic solutions were concentrated in vacuo, and then vacuum distilled to yield a colorless liquid (8.13 g, 70%). b.p. 62-72 °C at 0.6 mm Hg. To a solution of the above compounds (8.11 g, 41.5 mmol) in ether (80 mL) at -78 °C was added 1.7 M t-butyllithium (48.8 mL, 83 mmol, 2 eq) such that the temperature did not exceed -70 °C. After stirring for 15 minutes, a solution of DMF (6.5 mL, 83 mmol, 2 eq) in ether (20 mL) was added, and the mixture allowed to warm to room temperaure over 2 hours. The mixture was poured into water and the phases separated. The organic solution was dried over MgS04 and concentated in vacuo. The residue was purified by flash chromatography on silica gel eluting with 10% ether in hexanes to yield benzof uran-6-carboxaldehyde (1.22 g) and benzofuran-4-carboxaldehyde (1.86 g), both as colorless oils. Example 135B trans, trans- 1 -fN-Methvl-N- p ropylaminocarbonylmethvh-2-f4-methoxyphenylV4-f4- beπzofuranyhpyrrolidine-3-carboxylic acid The title compound was prepared using the procedures described in Examples 1 and 49 substituting the compound resulting from Example 135A in Example 49A for piperonal. 1 H NMR (300 MHz, CDCI3) (minor rotamer) δ 7.59 (1 H, t, J=3Hz), 7.4-7.2 (6H, m), 6.8 (2H, d, J=8Hz), 4.03 (1 H, m), 3.94 (1 H, dd, J=8Hz, 3Hz), 3.77 (3H, s), 3.61 (1 H, dd, J=8Hz, 7 3Hz), 3.42 (1 H, dd, J=11 Hz, 5Hz), 3.40-2.90 (5H, m), 2.82 (2.81 ) (3H, s), 1.50 (2H, septet, J=7Hz), 0.82 (0.75) (3H, t, J=7Hz). MS (DCI/NH3) m/e 451 (M+H) + . Anal.calc. for C26H30N2O5 • AcOH: C, 65.87; H, 6.71 ; N ,5.49. Found: C, 66.04; H, 6.42; N, 5.60. s Example 136 frans.frans-1 -fN-Methyl-N-propylaminocarbonylmethvπ-2-f4-methoxyphenylV4-f6- benzofuranynpyrrolidine-3-carboxylic acid The title compound was prepared using the procedures described in Examples 1 and 49 substituting benzof uran-6-carboxaldehyde, prepared as described in Example 135A, in Example 49A for piperonal. 1 H NMR (300 MHz, CDCI3) (minor rotamer) δ 7.65 (1 H, bd), 7.60 (1 H, d, J=2Hz), 7.55 (1 H, d, J=8Hz), 7.35 (3H, m), 6.85 (2H, dd, J=8Hz, 3Hz), 6.75 (1 H, dd, J=3Hz, 2Hz), 3.83 (2H, m), 3.79 (3H, s), 3.60-3.0 (7H, m), 2.91 (2.83) (s, 3H), 1.51 (2H, septet, J=7Hz), 0.83 (0.78) (3H, t, J=7Hz). MS (DCI/NH3) m/e 451 (M+H) + . Anal.calc. for C26H30N2O5 • 0.5 H 2 0: C, 67.96; H, 6.80; N, 6.10. Found: C, 67.90; H, 6.71 ; N, 6.07. Example 137 frans.frans-1-fN-Methyl-N-propylaminocarbonylmethylV2-(4-methoxyphenylV4-f6- benzo-2.3-dihvdrofuranyl)pyrro1idine-3-carboxylic acid The title compound was prepared by catalytic hydrogenation (4 atmospheres of H2 in AcOH, followed by preparative hplc) of the compound resulting from Example 136 1 H NMR (300 MHz, CDCI3) (minor rotamer) δ 7.49 (7.47) (2H, d, J=8Hz), 7.19 (1 H, d, J=8Hz), 7.00 (1 H, m), 7.82 (3H, m), 5.40 (1 H, dd, J=11 Hz, 7Hz), 4.58 (2H, t, J=8Hz), 4.18 (1H, m), 4.10 (1 H, m), 3.88 (1 H, m), 3.79 (3H, s), 3.60 (1 H, m), 3.35 (1 H, m), 3.19 (2H, t, J=8Hz), 3.00 (4H, m), 2.91 (2.78) (s, 3H), 1.53 (1.40) (2H, septet, J=7Hz), 0.88 (0.78) (3H, t, J=7Hz). MS (DCI/NH3) m/e 453 (M+H) + . Anal.calc. for C26H32N2O5 - 1.25 TFA: C, 57.53; H, 5.63; N, 4.71. Found: C, 57.68; H, 5.68; N, 4.70. Example 138 frans frans-1-(N.N-Dibutylaminocarbonvlmethyn-2-f4-methoxvphenyn-4-f4- benzofuranvnpvrrolidine-3-carboxvlic acid The title compound was prepared by the procedures described in Examples 1 and 49 substituting benzofuran-4-carboxaldehyde in Example 49A for piperonal and substituting N,N-dibutyl bromoacetamide for N-methyl-N-propyl bromoacetamide. 1 H NMR (300 MHz, CDCI3) δ 7.62 (1 H, d, J=3Hz), 7.39 (1 H, dt, J=8Hz, 2Hz), 7.34 (3H, m), 7.26 (1 H, d, J=2Hz), 7.23 (1H, d, J=8Hz), 6.84 (2H, d, J=8Hz), 4.02 (1 H, ddd, J=8, 6Hz,4Hz), 3.89 (1 H, d, J=9Hz) 3.79 (3H, s), 3.67 (1 H, dd, J=10Hz, 3Hz), 3.44 (2H, m), 3.35-3.15 (3H, m), 3.00 (2H, m), 2.84 (1 H, d, J=14Hz), 1.43 (3H, m), 1.23 (3H, m), 1.08 (2H, m), 0.87 (3H, t, J=7Hz), 0.82 (3H, t, J=7Hz). MS (DCI/NH3) m/e 507 (M+H) + . Anal.calc. for C30H38N2O5: C, 71.12; H, 7.56; N, 5.53. Found: C, 70.86; H, 7.45; N, 5.24. Example 139 frans.frans-1-fN.N-Dibutylaminocarbonylmethyπ-2-f4-methoxyphenyl -4-f4- benzofuranyl)pyrrolidine-3-carboxylic acid The title compound was prepared by the procedures described in Examples 1 and 49 substituting benzofuran-5-carboxaldehyde, prepared by the procedures described in Example 135A substituted 4- bromophenol for 3-bromophenol, in Example 49A for piperonal and substituting N,N-dibutyl bromoacetamide for N-methyl-N-propyl bromoacetamide. 1 H NMR (300 MHz, CDCI3) δ 7.64 (1 H, bd), 7.59 (1 H, d, J=2Hz), 7.43 (2H, m), 7.33 (2H, d, J=8Hz), 6.85 (2H, d, J=8Hz), 6.73 (1H, dd, J=3Hz, 1 Hz), 3.82 (1 H, d, J=11 Hz), 3.89 (1H, d, J=9Hz) 3.79 (3H, s), 3.53 (1 H, dd, J=10Hz, 3Hz), 3.44 (2H, m), 3.30 (1 H, m), 3.20-2.95 (5H, m), 2.82 (1 H, d, J=14Hz), 1.43 (3H, m), 1.23 (3H, m), 1.08 (2H, m), 0.87 (3H, t, J=7Hz), 0.82 (3H, t, J=7Hz). MS (DCI/NH3) m/e 507 (M+H) + . Anal.calc. for C30H38N2O5: C, 71.12; H, 7.56; N, 5.53. Found: C, 70.73; H, 7.45; N, 5.29. Example 140 frans.frans-1-fN.N-Dibutylaminocarbonylmethyl)-2-f4-methoxyphenyn-4-f6- benzofuranynpyrrolidine-3-carboxylic acid The title compound was prepared by the procedures described in Examples 1 and 49 substituting benzofuran-6-carboxaldehyde in Example 49A for piperonal and substituting N,N-dibutyl bromoacetamide for N-methyl-N-propyl bromoacetamide. 1 H NMR (300 MHz, CDCI3) δ 7.63 (1 H, bd), 7.59 (1 H, d, J=2Hz), 7.53 (1 H, d, J=8Hz), 7.36 (3H, m), 6.85 (2H, d, J=8Hz), 6.73 (1 H, dd, J=3Hz, 1 Hz), 3.82 (1 H, d, J=11 Hz), 3.89 (1 H, d, J=9Hz) 3.79 (3H, s), 3.53 (1 H, dd, J=10Hz, 3Hz), 3.44 (2H, m), 3.30 (1 H, m), 3.20-2.95 (5H, m), 2.80 (1 H, d, J=14Hz), 1.43 (3H, m), 1.23 (3H, m), 1.08 (2H, m), 0.87 (3H, t, J=7Hz), 0.82 (3H, t, J=7Hz). MS (DCI/NH3) m/e 507 (M+H) + . Anal.calc. for C30H38N2O5 ■ 0.75 H 2 0: C, 69.28; H, 7.65; N, 5.39. Found: C, 69.11 ; H, 7.33; N, 5.32. Example 141 frans.frans-1-fN.N-Dibutylaminocarbonylmethvn-2-f4-methoxvphenylV4-f6-benzo- 2.3-dihydrofuranyrιpyrrolidine-3-carboxylic acid The title compound was prepared by catalytic hydrogenation of the compound resulting from Example 140 (4 atmospheres of H2 in AcOH, followed by preparative hplc). 1 H NMR (300 MHz, CDCI3) δ 7.40 (2H, d, J=8Hz), 7.16 (1 H, d, J=8Hz), 6.97 (1 H, dd, J=8Hz, 2Hz), 6.89 (3H, m), 5.90 (1 H, bs) 4.57 (2H, t, J=9Hz), 4.93 (2H, m), 3.80 (3H, s), 3.70- 3.58 (2H, m), 3.40 (1 H, m), 3.30-2.90 (8H, m), 1.40 (2H, m), 1.29 (3H, m), 1.08 (2H, m), 0.92 (3H, t, J=7Hz), 0.82 (3H, t, J=7Hz). MS (DCI/NH3) m/e 509 (M+H) + . Anal.calc. for C30H40N2O5 • 0.85 TFA: C, 62.88; H, 6.80; N, 4.63. Found: C, 63.04; H, 6.66; N, 4.60. Example 142 frans.frans-1-ιN-Methyl-N-proPylaminocarbonylmethylV2-(4-methoxyphenvn-4-ι / 5- indanvnpyrrolidine-3-carboxylic acid Example 142A lndane-5-carboxaldehvde lndane-5-carboxaldehyde was prepared by formylation of indane under the conditions described for 2,3-dihydrobenzofuran in Example 52A. The resultant mixture of 4- and 5-carboxaldehydes was purified as follows: to a 6:1 mixture of indane-4-carboxaldehyde and indane-5- carboxaldehyde (3.46 g, 23 mmol) was added aniline (2.20 g, 23 mmol, 1 eq). The resultant solution slowly solidfied to a mixture of imines which was recrystallized from hot acetonitrile to yield the 5-aldimine as a white solid. The aldimine (2.65 g) was suspended in water (6 mL), and treated with 4 N. hydrochloric dioxane (10 mL). The mixture was boiled for 1 hour, cooled to room temperature, and poured into ether. The organic solution was dried over MgSθ 4 , filtered, and concentated in vacuo. Vacuum distillation of the residue afforded indane-5- carboxaldehyde (1.54 g, 88%) as a colorless liquid, b.p. 88-90 °C at 0.9 mm Hg. Example 142B trans, trans- 1-fN-Methyl-N-propylaminocarbonylmethyl)-2-(4-methoxyphenyπ-4-(5- indanyl)pyrrolidine-3-carboxylic acid The title compound was prepared by the procedures described in Examples 1 and 49 substituting indane-5-carboxaldehyde for piperonal in Example 49A. 1 H NMR (300 MHz, CDCI 3 ) (minor rotamer) δ 7.25-7.1 (5H, m), 6.78 (2H, d, J=8Hz), 3.8g (1H, d, J=8Hz), 3.75 (3H, s), 3.50- 2.gθ (6H, m), 2.88 (6H, t, J=6Hz), 2.82 (2.80) (3H, s), 2.04 (2H, t, J=8Hz), 1.48 (2H, septet, J=7Hz), 0.83 (0.73) (3H, t, J=7Hz). MS (DCI/NH3) m/e 451 (M+H) + , 473 (M+Na)+. Anal.calc. for C27H3 4 N2O4 - 2.5 H 2 0 : C, 65.44; H, 7.93; N, 5.65. Found: C, 65.36; H, 7.45; N, 5.53. Example 143 frans.frans-l-fN-Methyl-N-propylaminocarbonylmethvn^- -methoxyphenyll^-fβ- indolyhPvrrolidine-3-carboxvlic acid The title compound was prepared by the procedures described in Examples 1 and 49 substituting indole-6-carboxaldehyde, prepared by the method of Rapoport, J. Org. Chem. 51: 5106 (1986), for piperonal in Example 49A. 1 H NMR (300 MHz, CDCI3) (minor rotamer) δ 8.43 (1H, brs), 7.57 (1 H, d, J=8Hz), 7.43 (1H, s), 7.31 (2H, dd, J=6Hz, 3Hz), 7.22 (1 H, d, J=8Hz), 7.1 (1H, t, J=3Hz), 6.78 (2H,dd, J=6Hz, 3Hz), 6.45 (1H, m), 3.93 (1 H, dd, J=6Hz, 3Hz), 3.80 (1H, m), 3.73 (3H, s), 3.60-2.90 (6H, m), 2.86 (2.82) (3H, s), 1.47 (2H, septet, J=7Hz), 0.83 (0.73) (3H, t, J=7Hz). MS (DCI/NH3) m/e 450 (M+H) + . Anal.calc. for C26H31 N3O4 • 0.75 H 2 0: C, 67.44; H, 7.07; N, 9.07. Found: C, 67.42; H, 7.09; N, 8.91. Example 144 frans. frans- 1-f N-Methyl-N- p ropylaminocarbonylmethvn-2-(4-methoxyphenylV4- ( 3.4-diftuoro p henvn p yrrolidine-3-carboxylic acid The title compound was prepared by the procedures described in Examples 1 and 48 substituting 3,4-difluorobenzaldehyde for piperonal in Example 49A. 1 H NMR (300 MHz, CDCI 3 ) (minor rotamer) δ 7.60-7.3 (4H, m), 7.13 (1 H, q, J=9Hz), 6.90 (2H, d, J=8Hz), 3.90 (1 H, m), 3.7g (3H, s), 3.60-2.95 (6H, m), 2.92 (2.78) (3H, s), 1.55 (2H, septet, J=7Hz), 0.88 (0.73) (3H, t, J=7Hz). MS (DCI/NH3) m/e 447 (M+H) + . Anal.calc. for C24H28F2N2O4 ■ 1.80 H 2 0: C, 60.19; H, 6.65; N, 5.85. Found: C, 60.13; H, 6.34; N, 5.84. Example 145 frans.frans-1- N-Methvl-N-propvlaminocarbonvlmethvn-2-f4-methoxvphenvn-4- phenyl)pyrrolidine-3-carboxylic acid The title compound was prepared by the procedures described in Examples 1 and 49 substituting benzaldehyde for piperonal in Example 49A. 1 H NMR (300 MHz, CDCI3) (minor rotamer) δ 7.53 (4H, d, J=6Hz), 7.40-7.20 (3H, m), 6.88 (2H, d, J=8Hz), 3.90 (1 H, m), 3.79 (3H, s), 3.70- 2. 5 (8H, m), 2.gθ (2.7g) (3H, s), 1.50 (2H, sept, J=7Hz), 0.87 (0.72) (3H, t, J=7Hz). MS (DCI/NH3) m/e 411 (M+H) + . Anal.calc. for C24H30 2O4 • 2.00 H 2 0: C, 64.55; H, 7.67; N, 6.27. Found: C, 64.37; H, 7.43; N, 6.29. Example 146 frans.frans-1-fN-Methyl-N-propylaminocarbonylmethvπ-2-(4-methoxyphenyn-4-ι , 4- hvdroxyphenvnpyrrolidine-3-carboxvlic acid The title compound was prepared by the procedures described in Examples 1 and 49 substituting 4-hydroxybenzaldehyde for piperonal in Example 49A. 1 H NMR (300 MHz, CDCI3-CD3OD) (minor rotamer) δ 7.35 (2H, d, J=8Hz), 7.28 (2H, dd, J=7Hz, 3Hz), 6.90 (2H, dd, J=7Hz, 3Hz), 6.89 (2H, d, J=8Hz), 3.81 (3H, s), 3.65 (1 H, d, J=8Hz), 3.70-3.00 (8H, m), 2.92 (2.83) (3H, s), 1.50 (2H, septet, J=7Hz), 0.87 (0.77) (3H, t, J=7Hz). MS (DCI/NH3) m/e 427 (M+H) + . Anal.calc. for C24H30N2O5 - 1.00 H 2 0: C , 64.85; H, 7.26; N, 6.30. Found: C, 64.82; H, 7.39; N, 6.46. Example 147 frans.frans-1 -fN-Methyl-N-propvlaminocarbonylmethyn-2-r4-methoxyphenyn-4. 2.4-dimethoxyphenvnpyrrolidine-3-carboxylic acid The title compound was prepared by the procedures described in Examples 1 and 49 substituting 2,4-dimethoxybenzaldehyde for piperonal in Example 49A. 1 H NMR (300 MHz, CDCI3-CD3OD) (minor rotamer) δ 7.61 (1 H, d, J=8Hz), 7.30 (2H, d, J=8Hz), 6.82 (2H, d, J=8Hz), 6.55 (1 H, d, J=8Hz), 6.45 (1 H, d, J=3Hz), 3.90 (1 H, m), 3.81 (3H, s), 3.79 (3H, s), 3.77 (3H, s), 3.70-2.90 (8H, m), 2.85 (3H, s), 1.50 (2H, sept, J=7Hz), 0.87 (0.77) (3H, t, J=7Hz). MS (DCI/NH3) m/e 471 (M+H) + . Anal.calc. for C26H34N2O6 • 0.75 H 2 0: C, 64.51 ; H, 7.39; N, 5.79. Found: C, 64.65; H, 7.07; N, 5.75. Example 148 fraπs.frans-1-fN.N-Dibutylaminocarbonylmethyn-2-f4-methoxvphenyn-4-f5-benzQ- 2.3-dihydrofuranyπpyrrolidine-3-carboxylic acid The title compound was prepared by the procedures described in Examples 1 and 49 substituting 2,3-dihydrobenzofuran-5- carboxaldehyde for piperonal in Example 49A. " Η NMR (300 MHz, CDCI3) δ 7.31 (2H, d, J=8Hz), 7.27 (1 H, d, J=2Hz), 7.18 (1 H, dd, J=7Hz, 3Hz), 6.86 (2H, d, J=8Hz), 6.72 (1 H, d, J=8Hz), 4.56 (2H, t, J=7Hz), 3.78 (3H, s), 3.62 (1 H, m), 3.50-3.25 (4H, m), 3.17 (2H, t, J=7Hz), 3.15-2.90 (5H, m), 2.79 (1 H, d, J=14Hz), 1.43 (3H, m), 1.26 (3H, m), 1.08 (2H, m), 0.87 (3H, t, J=7Hz), 0.81 (3H, t, J=7Hz). MS (DCI/NH3) m/e 509 (M+H) + . Anal.calc. for C30H40N2O5 - 0.25 H 2 0: C, 70.22; H, 7.95; N, 5.46. Found: C, 70.21 ; H, 7.92; N, 5.36. Example 149 trans.transA -(N.N-Dibutylaminocarbonylmethyl 2-(4-methoxyphenyl -(4- methoxvphenvnpvrrolidine-3-carboxvlic acid The title compound was prepared by the procedures described in Examples 1 and 49 substituting 4-methoxybenzaldehyde for piperonal in Example 49A. 1 H NMR (300 MHz, CDCI3) δ 7.38 (2H, d, J=8Hz), 7.30 (2H, d, J=8Hz), 6.87 (4H, dd, J=7Hz, 3Hz), 3.78 (3H, s), 3.76 (3H, s), 3.63 (1 H, m), 3.50-3.20 (4H, m), 3.15-2.gθ (5H, m), 2.78 (1 H, d, J=14Hz), 1.43 (3H, m), 1.27 (3H, m), 1.09 (2H, m), 0.87 (3H, t, J=7Hz), 0.81 (3H, t, J=7Hz). MS (DCI/NH3) m/e 497 (M+H) + . Anal.calc. for C29H40N2O5: C, 70.13; H, 8.12; N, 5.64. Found: C, 69.78; H, 8.10; N, 5.54. Example 150 frans. frans-1-fN. N-DibutvlaminQcarbonylmethvn-2-f4-methoχyphenyn-4-3.4- difluoro p henynpyrrolidine-3-carboxylic acid The title compound was prepared by the procedures described in Examples 1 and 49 substituting 3,4-difluorobenzaldehyde for piperonal in Example 49A. 1 H NMR (300 MHz, CDCI3) δ 7.35 (1 H, m), 7.30 (2H, d, J=8Hz), 7.20-7.00 (2H, m), 6.87 (2H, d, J=8Hz), 3.78 (3H, s), 3.7g (1 H, m), 3.62 (1 H, m), 3.50-3.30 (3H, m), 3.23 (1 H, m), 3.15-2.90 (4H, m), 2.78 (1 H, d, J=14Hz), 1.43 (2H, m), 1.27 (4H, m), 1.08 (2H, m), 0.85 (3H, t, J=7Hz), 0.80 (3H, t, J=7Hz). MS (DCI/NH3) m/e 503 (M+H) + . Anal.calc. for C 2 8H36F2N2θ - • 1 H 2 0: C, 64.60; H, 7.36; N, 5.38. Found: C, 64.59; H, 7.20; N, 5.35. Example 151 frans.frans-1-,N.N-Dibutylaminocarbonylmethvπ-2-f4-methoxyphenyn-4-f2.4- dimethoxyphenyhpvrrolidine-3-carboxylic acid The title compound was prepared by the procedures described in Examples 1 and 49 substituting 2,4-dimethoxybenzaldehyde for piperonal in Example 4gA. 1 H NMR (300 MHz, CDCI3) δ 7.37 (2H, d, J=8Hz), 7.20 (1 H, d, J=8Hz), 6.92 (2H, d, J=8Hz), 6.60 (1 H, d, J=3Hz), 6.49 (1 H, dd, J=6Hz, 2Hz), 5.35 (1 H, d, J=8Hz), 4.20 (3H, m), 4.10 (3H, s), 3.83 (3H, s), 3.81 (3H, s), 3.75 (3H, m), 3.17 (2H, hep, J=7Hz), 3.05 (2H, t, J=7Hz), 1.30 (4H, m), 1.07 (4H, m), 0.87 (3H, t, J=7Hz), 0.80 (3H, t, J=7Hz). MS (DCI/NH3) m/e 527 (M+H) + . Anal.calc. for C30H42N2O6 - 1 .30 TFA: C, 58.02; H, 6.47; N, 4.15. Found: C, 57.92; H, 6.43; N, 4.07. Example 152 frans.frans-1- N.N-Dibutylaminocarbonylmethvn-2-phenyl-4-(1.3-benzodioxol-5- yhpyrrolidine-3-carboxylic acid The title compound was prepared by the procedures described in Examples 1 and 49 substituting ethyl benzoylacetate in Example 49B. 1 H NMR (300 MHz, CDCI3) δ 7.50-7.25 (5H, m), 7.04 (1 H, d, J=3Hz), 6.87 (1 H, dd, J=7Hz, 3Hz), 6.74 (1 H, d, J=8Hz), 5.94 (1 H, d, J=4Hz), 5.92 (1H, d, J=4Hz), 3.85 (1H, d, J=8Hz), 3.64 (1 H, m), 3.42 (3H, m), 3.27 (2H, m), 3.20-2.90 (5H, m), 2.81 (1H, d, J=14Hz), 1.43 (2H, m), 1.27 (4H, m), 1.05 (2H, m), 0.85 (3H, t, J=7Hz), 0.80 (3H, t, J=7Hz). MS (DCI/NH3) m/e 481 (M+H) + . Anal.calc. for C28H36N2O5: C, 69.98; H, 7.55; N, 5.83. Found: C, 69.69; H, 7.63; N, 5.71. Example 153 frans.frans-1-fN.N-Dibutvlaminocarbonvlmethvn-2- p henvl-4-f5-benzo-2.3- dihvdrofuranvnpvrrolidine-3-carboxvlic acid The title compound was prepared by the procedures described in Examples 1 and 49 substituting ethyl benzoylacetate in Example 49B and 2,3-dihydrobenzofuran-5-carboxaldehyde for piperonal in Example 4 A. " «H NMR (300 MHz, CDCI 3 ) δ 7.53 (2H, m), 7.40 (4H, m), 7.13 (1H, dd, J=7Hz, 3Hz), 6.72 (1H, d, J=8Hz), 5.40 (1H, d, J=10Hz), 4.56 (2H, t, J=8Hz), 4.18 (1 H, d, J=14Hz), 4.07 (2H, m), 3.7g (2H, m), 3.48 (1H, d, J=14Hz), 3.35 (1H, m), 3.28 (3H, m), 2.95 (2H, m), 1.47 (2H, m), 1.28 (4H, m), 1.10 (2H, m), 0.93 (3H, t, J=7Hz), 0.78 (3H, t, J=7Hz). MS (DCI/NH3) m/e 479 (M+H) + . Anal.calc. for C2 9 H 38 N2O4 - 1.10 TFA: C, 62.04; H, 6.52; N, 4.64. Found: C, 61.89; H, 6.44; N, 4.57. Example 154 frans.frans-1- l N.N-Dibutylaminocarbonylmethvn-2-(4-t-butylPhenvn-4-(5-benzo- 2.3-dihydrofuranyπpyrrolidine-3-carboxylic acid The title compound was prepared by the procedures described in Examples 1 and 49 substituting t-butyl benzoylacetate, prepared by the method of Krapcho et al., Org. Syn. 47:20 (1967) starting from 4-t- butylacetophenone, in Example 49B and 2,3-dihydrobenzofuran-5- carboxaldehyde for piperonal in Example 4gA. 1 H NMR (300 MHz, CDCI 3 ) δ 7.60-7.30 (6H, m), 6.90 (1H, m), 4.50 (2H, m), 3.95 (1H, m), 3.85-2.95 (11H, m), 2.90 (1 H, d, J=14Hz), 1..58 (2H, m), 1.50 (7H, m), 1.41 (6H, s), 1.10 (2H, m), 1.00 (3H, t, J=7Hz), 0.90 (3H, t, J=7Hz). MS (DCI/NH 3 ) m/e 535 (M+H) + . Anal.calc. for C33H46N2O4 • 0.25 H 2 0: C, 73.50; H, 8.69; N, 5.19. Found: C, 73.57; H, 8.58; N, 5.14. Example 155 frans.frans-2-fN.N-Dibutvlaminocarbonylmethyl)-2-f4-methoxyphenyn-4-f4- fluorophenyl)pyrrolidine-3-carboxylic acid The title compound was prepared by the procedures described in Examples 1 and 49 substituting 4-fluorobenzaldehyde for piperonal in Example 49A. " »H NMR (300 MHz, CDCI 3 ) δ 7.50 (1 H, m), 7.42 (1 H, dd, J=7Hz, 3Hz), 7.36 (2H, d, J=8Hz), 7.01 (3H, t, J=8Hz), 6.87 (1 H, d, J=8Hz), 3.83 (1H, m), 3.8 (3H, s), 3.67 (1 H, m), 3.47 (3H, m), 3.30-2.90 (5H, m), 2.82 (1H, d, J=14Hz), 1.43 (2H, m), 1.28 (4H, m), 1.08 (2H, m), 0.90 (3H, t, J=-7Hz), 0.82 (3H, t, J=7Hz). MS (DCI/NH3) m/e 485 (M+H) + . Anal.calc. for C28H37FN2O4: C, 69.40; H, 7.70; N, 5.78. Found: C, 69.03; H, 8.00; N, 5.74. Example 156 frans.frans-1-fN.N-Dibutylaminocarbonylmethyn-2-f3-furylV4-f1.3-benzodioxol-5- ynpyrrolidine-3-carboxylic acid The title compound was prepared by the procedures described in Examples 1 and 49 substituting β-oxo-3-furanpropionate in Example 49B. 1 H NMR (300 MHz, CDCI3) δ 7.41 (2H, m), 6.97 (1H, d, J=3Hz), 6.85 (1H, dd, J=7Hz, 3Hz), 6.72 (1H, d, J=8Hz), 6.42 (1H, s), 5.94 (1H, d, J=4Hz), 5.92 (1 H, d, J=4Hz), 3.90 (1 H, m), 3.70-3.25 (5H, m), 3.20-2.90 (4H, m), 2.85 (1 H, d, J=14Hz), 1.43 (2H, m), 1.40-1.05 (6H, m), 0.90 (6H, m). MS (DCI/NH3) m/e 471 (M+H) + . Anal.calc. for C26H34N2O6: C, 66.36; H, 7.28; N, 5.95. Found: C, 66.09; H, 7.24; N, 5.87. Example 157 frans. frans-1-(N N-Dibutylaminocarbonylmethvn-2-fisopropvn-4-ι / 1.3-benzodioxor- 5-vnpvrrolidine-3-carboxvlic acid The title compound was prepared by the procedures described in Examples 1 and 49 substituting ethyl isobutyrylacetate in Example 49B. 1H NMR (300 MHz, CDCI3) δ 6.85 (1 H, d, J=2Hz), 6.76 (1H, dd, J=6Hz, 2Hz), 6.71 (1 H, d, J=8Hz), 5.92 (2H, s), 3.75 (1 H, d, J=14Hz), 3.66 (1H, q, J=7Hz), 3.42 (3H, m), 3.25 (3H, m), 3.11 (2H,m), 2.83 (1 H, t, J=7Hz), 1.88 (1 H, m), 1.55 (4H, m), 1.32 (4H, m), 0.92 (12H, m). MS (DCI/NH3) m/e 447 (M+H) + . Anal.calc. for C-25H38N2O5 • 0.50 H 2 0: C, 65.91 ; H, 8.63; N, 6.15. Found: C, 66.07; H, 8.10; N, 6.03. Example 158 frans.frans-1-fN.N-Dibutylaminocarbonylmethvn-2-f4-t-butylphenvn-4-M .3- benzodioxol-5-vnpyrrolidine-3-carboxylic acid The title compound was prepared by the procedures described in Examples 1 and 49 substituting ethyl 4-t-butylbenzoylacetate, prepared by the method of Krapcho et al., Org. Syn. 47: 20 (1967) starting with 4- t-butylacetophenone), in Example 4gB. 1 H NMR (300 MHz, CDCI3) δ 7.32 (4H, d, J=3Hz), 7.04 (1H, d, J=2Hz), 6.87 (1 H, dd, J=8Hz, 3Hz), 6.74 (1H, d, J=9Hz), 5.94 (1 H. d, J=4Hz), 5.92 (1 H, d, J=4Hz), 3.77 (1H, d, J=14Hz), 3.65-3.25 (5H, m), 3.15-2.85 (4H, m), 2.73 (1 H, d, J=14Hz), 1.45 (2H, m), 1.29 (13H, s), 1.00 (2H, m), 0.86 (3H, t, J=7Hz), 0.76 (3H, t, J=7Hz). MS (DCI/NH3) m/e 537 (M+H) + . Anal.calc. for C32H44N2O5: C, 71.61 ; H, 8.26; N, 5.22. Found: C, 71.43; H, 8.09; N, 5.11. Example 159 trans, trans- l -fN N-Dibutvlaminocarbonylmethyn^-^-t-butylphenvn^-fS-benzo- 2.3-dihvdrofuranynpyrrolidine-3-carboxylic acid The title compound was prepared by the procedures described in Examples 1 and 49 substituting ethyl isobutyrylacetate in Example 49B and 2,3-dihydrobenzofuran-5-carboxaldehyde for piperonal in Example 49A. 1H NMR (300 MHz, CDCI3) δ 7.30 (1 H, s), 7.13 (1 H, dd, J=7Hz, 2Hz), 6.82 (1 H, d, J=8Hz), 4.68 (2H, t, J=8Hz), 4.48 (1 H, s), 3.19 (3H, m), 3.80 (3H, m), 3.48 (2H, m), 3.3 (5H, m), 2.41 (1 H, m), 1.65 (4H, m), 1.44 (4H, m), 1.21 (3H, d, J=5Hz), 1.17 (3H, d, J=5Hz), 1.05 (6H, m). MS (DCI/NH3) m/e 445 (M+H) + . Anal.calc. for C26H40N2O4 • 1.2 TFA: C, 58.67; H, 7.14; N, 4.8.2 Found: C, 58.54; H, 7.25; N, 4.74. Example 160 trans, frans-1 -■ N.N-Dibutylaminocarbonylmethyπ-2- ( anti-4-methoxycyclohexyl)-4- (1.3-benzodioxol-5-yl)pyrrolidine-3-carboxylic acid Example 160A svn and anti Ethyl 4-methoxycvclohexanoylacetate Syn, anti-4-Methoxycyclohexane carboxylic acid (5.00 g, 31.6 mmol) and carbonyldiimidazole (6.15 g, 37.9 mmol, 1.2 eq) were stirred in anhydrous tetrahydrofuran (50 mL) for 6 hours at room temperature. At the same time, magnesium chloride (3.01 g, 31.6 mmol) and ethyl malonate potassium salt (7.52 g, 44.2 mmol, 1.4 equivalents) were stirred in anhydrous tetrahydrofuran (75 mL) for 6 hours at 50 °C. The mixture was cooled to room temperature, and the imidazole-acid mixture added to it. The reaction stirred overnight at room temerature. 5 The solvents were removed under reduced pressure, and the residue was taken up in chloroform/water. The organic phase washed with 5% potassium bisulfate, water, and brine, dried with magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by flash chromatography on 175 g silica gel, eluting with 20% ι o ethyl acetate in hexanes. Pure fractions of the syn and anti methoxycyclohexyl β-keto esters were obtained. The solvents were removed under reduced pressure to yield the trans-4- methoxycyclohexyl β-keto ester (914 mg) as a colorless oil and the cis 4-methoxycyclohexyl β keto ester (1.07 g) as a colorless oil. 1 5 Example 160B frans. frans-1-fN.N-Dibutylaminocarbonylmethvπ-2-ιanti-4-methoxycvclohexyπ-4- ( 1.3-benzodioxol-5-vnpvrrolidine-3-carboxvlic acid 20 The title compound was prepared by the procedures described in Examples 1 and 49 substituting the anti-compound resulting from Example 160A in Example 49B. " Η NMR (300 MHz, CDCI 3 ) δ 6.84 (1H, d, J=2Hz), 6.76 (1H, dd, J=7Hz, 2Hz), 6.61 (1 H, d, J=8Hz), 5.92 (2H, s), 3.69 (2H, m), 3.50-3.27 (5H, m), 3.26 (3H, s), 3.25-3.00 (3H, m), 2.88 (1H, 25 m), 1.95 (2H, m), 1.62 (7H, m), 1.33 (9H, m), 0.97 (3H, t, J=7Hz), 0.92 (3H, t, J=7Hz). MS (DCI/NH3) m/e 517 (M+H) + . Anal.calc. for C29H44N2O 6 • 0.50 H 2 0: C, 66.26; H, 8.63; N, 5.33. Found: C, 66.27; H, 8.50; N, 5.13. Example 161 30 frans. frans-1-fN.N-Dibutylaminocarbonylmethyn-2-isvn-4-methoxycvclohexyn-4- (1.3-benzodioxol-5-ynpvrrolidine-3-carboxylic acid The title compound was prepared by the procedures described in Examples 1 and 49 substituting the syn-compound resulting from Example 160A in Example 49B. ^H NMR (300 MHz, CDCI3) δ 6.84 (1H, d, 35 J-=2Hz), 6.77 (1H, dd, J=6Hz, 2Hz), 6.61 (1 H, d, J=8Hz), 5.92 (2H, s), 3.65 (2H, m), 3.42 (2H, m), 3.32 (3H, s), 3.30-3.00 (6H, m), 2.82 (1H, m), 2.10 (2H, m), 1.83 (2H, m), 1.52 (6H, m), 1.33 (4H, m), 1.20-1.00 (4H, m), 0.96 (3H, t, J=7Hz), 0.91 (3H, t, J=7Hz). MS (DCI/NH3) m/e 517 (M+H) + . Anal.calc. for C29H44N2O6 • 0.30 H 2 0: C, 66.72; H, 8.61 ; N, 5.37. Found: C, 66.76; H, 8.65; N, 5.28. Example 162 frans.frans-1-fN.N-Dibutvlaminocarbonylmethvn-2.4-dif5-benzo-2.3- dihydrofuranvnpvrrolidine-3-carboxylic acid Example 162A 5-Acetvl-2.3-dihvdrobenzofuran To a 0 °C solution of acetyl chloride (1.64 L, 23.0 mmol, 1.3 equivalents) in methylene chloride (30 mL) was added stannic chloride (2.49 mL, 21.3 mmol, 1.2 equivalents), maintaining the temperature below 5 °C. The solution was stirred 15 minutes at 0 °C, and then a solution of 2,3-dihydrofuran (2.00 mL, 17.7 mmol) in methylene chloride (5 mL) was added dropwise while maintaining the temperature below 8 °C. The dark red solution was stirred 1 hour at 2 °C and then poured into 50 mL of ice water. The reaction was stirred an additional 30 minutes, and the layers were separated. The organic layer was washed with water and aqueous sodium bicarbonate, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by flash chromatography on 150 g silica gel, eluting with 18% ethyl acetate in hexanes. The solvents were removed under reduced pressure to yield the title compound (2.68 g, 93%) as a yellow solid. Example 162B frans frans-1 -fN.N-Dibutylaminocarbonylmethyn-2.4-dif5-benzo-2.3- dihydrofuranynpyrrolidine-3-carboxylic acid The title compound was prepared by the procedures described in Examples 1 and 49 substituting the compound resulting from Example 162A in Example 49B and 2,3-dihydrobenzofuran-5-carboxaldehyde for piperonal in Example 49A. 1 H NMR (300 MHz, CDCI3) δ 7.43 (1 H, s), 7.38 (1 H, s), 7.06 (2H, m), 6.75 (1H, d, J=6Hz), 6.70 (1H, d, J=6Hz), 5.40 (1H, d, J=9Hz), 4.58 (4H, q, J=7Hz), 4.16 (1 H, d, J=14Hz), 4.09 (2H, m), 3.82 (2H, m), 3.57 (1 H, d, J=14Hz), 3.38 (1H, m), 3.30-3.05 (6H, m), 2.95 (2H, q, J=6Hz), 1.50 (2H, m), 1.30 (4H, m), 1.15 (2H, m), 0.94 (3H, t, J=7Hz), 0.83 (3H, t, J=7Hz). MS (DCI/NH3) m/e 521 (M+H) + . Anal.calc. for C31 H40N2O5 • 1.25 TFA: C, 60.67; H, 6.27; N, 4.22. Found: C, 60.49; H, 6.18; N, 4.13. Example 163 frans.frans-1-fN.N-Dibutylaminocarbonylmethvn-2-r3-furvn-4-f5-benzo-2.3- dihydrofuranvnpvrrolidine-3-carboxvlic acid The title compound was prepared by the procedures described in Examples 1 and 49 substituting ethyl β-oxo-3-furanpropionate in Example 49B and 2,3-dihydrobenzofuran-5-carboxaldehyde for piperonal in Example 4gA. H NMR (300 MHz, CDCI3) δ 7.42 (1 H, m), 7.38 (1 H, m), 7.13 (1H, s), 7.16 (1 H, dd, J=7Hz, 3Hz), 6.70 (1 H, d, J=8Hz), 6.41 (1 H, m), 4.57 (2H, t, J=7Hz), 3.g5 (1 H, d, J=8Hz), 3.63 (1 H, m), 3.55 (1 H, d, J=14), 3.50-3.25 (4H, m), 3.18 (2H, t, J=6Hz), 3.15-2.05 (3H, m), 2.87 (1 H, d, J=14Hz), 1.45 (4H, m), 1.35-1.10 (4H, m), 0.85 (6H, m). MS (DCI/NH3) m/e 469 (M+H) + . Anal.calc. for C27H36N2O5 ■ 0.25 H 2 0: C, 68.55; H, 7.78; N, 5.92. Found: C, 68.62; H, 7.68; N, 5.82. Example 164 frans.frans-1-fN.N-Dibutylaminocarbonylmethyn-2-f4-methoxyphenyn-4-(3- fluorophenynpyrrolidine-3-carboxylic acid The title compound was prepared by the procedures described in Examples 1 and 49 substituting 3-fluorobenzenecarboxaldehyde for piperonal in Example 49A. 1 H NMR (300 MHz, CDCI3) δ 7.30 (2H, d, J=8Hz), 7.22 (2H, m), 6.91 (1 H, m), 6.86 (2H, d, J=8Hz), 3.79 (1 H, m), 3.78 (3H, s), 3.68 (1 H, m), 3.55-3.37 (3H, m), 3.29 (1 H, m), 3.15-2.90 (5H, m), 2.78 (1 H, d, J=14Hz), 1.43 (2H, m), 1.25 (4H, m), 1.07 (2H, m), 0.87 (3H, t, J=7Hz), 0.80 (3H, t, J=7Hz). MS (DCI/NH3) m/e 485 (M+H) + . Anal.calc. for C28H37 N2O4 • 0.25 H 2 0: C, 68.76; H, 7.73; N, 5.73. Found: C, 68.87; H, 7.69; N, 5.67. Example 165 frans.frans-1-fN.N-Dibutylaminocarbonylmethvn-2-f4-methoxyphenvn-4-f3- pyridvnpvrrolidine-3-carboxylic acid The title compound was prepared by the procedures described in Examples 1 and 49 substituting 3-pyridinecarboxaldehyde for piperonal in Example 49A. The nitro styrene was prepared by the method of Bourguignon ,et al., Can. J. Chem. 63: 2354 (1985). 1 H NMR (300 MHz, CDCI 3 ) δ 8.82 (1 H, bs), 8.73 (1 H, bd, J=9Hz), 8.62 (1 H, bd, J=7Hz), 7.78 (1 H, bdd, J=9Hz, 3Hz), 7.38 (2H, d, J=10Hz), 6.90 (2H, d, J=10Hz), 4.39 (1 H, d, J=12Hz), 3.95 (1H, m), 3.80 (3H, s), 3.79 (1H, m), 3.68 (1 H, d, J=18Hz), 3.50-3.30 (3H, m), 3.25-2.90 (6H, m), 1.47 (2H, m), 1.31 (4H, m), 1.20 (2H, m), 0.92 (3H, t, J=7Hz), 0.83 (3H, t, J=7Hz). MS (DCI/NH3) m/e 468 (M+H) + . Anal.calc. for C27H37N3O4 • 1.65 TFA: C, 55.50; H, 5.94; N, 6.41. Found: C, 55.53; H, 5.90; N, 6.27. Example 166 frans. frans-1-fN.N-Dibutvlaminocarbonvlmethvn-2-f2-fluorophenvn-4-f 1.3- benzodioxol-5-vnpyrrolidine-3-carboxylic acid The title compound was prepared by the procedures described in Examples 1 and 49 substituting ethyl 2-fluorobenzoylacetate in Example 49B. 1 H NMR (300 MHz, CDCI3) δ 7.52 (1H, dt, J=7Hz, 3Hz), 7.25 (1 H, m), 7.13 (1 H, dt, J=7Hz, 3Hz), 7.02 (2H, m), 6.88 (1 H, dd, J=7Hz, 3Hz), 6.73 (1 H, d, J=8Hz), 5.g3 (1 H, d, J=4Hz), 5.92 (1H, d, J=4Hz), 4.25 (1 H, d, J=9Hz), 3.68 (1 H, m), 3.42 (3H, m), 3.39 (1 H, m), 3.20-2.95 (4H, m), 2.91 (1 H, d, J=14Hz), 1.45 (3H, m), 1.26 (3H, m), 1.08 (2H, m), 0.87 (3H, t, J=7Hz), 0.81 (3H, t, J=7Hz). MS (DCI/NH3) m/e 4 g (M+H) + . Anal.calc. for C28H35FN2O5 • 0.25 H 2 0: C, 66.85; H, 7.11 ; N, 5.57. Found: C, 66.51 ; H, 6.67; N, 5.18. Example 167 frans. frans-1-fN.N-Dibutylaminocarbonylmethyn-2-f3-fluorophenvn-4-(1.3- benzodioxol-5-vnpvrrolidine-3-carboxylic acid The title compound was prepared by the procedures described in Examples 1 and 49 substituting ethyl 3-fluorobenzoylacetate in Example 49B. " Η NMR (300 MHz, CDCI3) δ 7.38 (1 H, m), 7.18 (1 H, d, J=7Hz), 7.15 (1 H, m), 7.00 (1 H, d, J=2Hz), 6.95 (1H, m), 6.86 (1 H, dd, J=7Hz, 2Hz), 6.75 (1 H, d, J=8Hz), 5.93 (1 H, d, J=4Hz), 5.92 (1 H, d, J=4Hz), 3.94 (1H, d, J=14Hz), 3.63 (1 H, m), 3.42 (3H, m), 3.35-2.95 (5H, m), 2.87 (1 H, d, J=14Hz), 1.44 (3H, m), 1.27 (3H, m), 1.10 (2H, m), 0.88 (3H, t, J=7Hz), 0.81 (3H, t, J=7Hz). MS (DCI/NH3) m/e 499 (M+H) + . Anal.calc. for C28H35FN2O5: C, 67.45; H, 7.08; N, 5.62. Found: C, 67.32; H, 7.05; N, 5.40. Example 168 frans.frans-1-f4-N.N-Dibutvlaminophenvn-2-f4-methoxvphenvn-4-f1.3- beπzodioxol-5-vnpvrrolidine-3-carboxvlic acid 5 4-Nitro-1-fluorobenzene, ethyl trans. trans-2-{4- methoxyphenyl)-4-(1 ,3-benzodioxol-5-yl)-pyrrolidine-3-carboxylate (the compound resulting from Example 6A), and diisopropylethylamine are heated in dioxane to give ethyl trans. rans-2-(4-methoxyphenyl)-4- (1 ,3-benzodioxol-5-yl)-1 -(4-nitrophenyl)-pyrrolidine-3-carboxylate. ι o The nitro compound is hydrogenated to give the corresponding aminophenyl compound. The aminophenyl compound is reacted with butyraldehyde and sodium cyanoborohydride according to the method of Borch, J. Am Chem. Soc. 93: 2897 (1971) to give the corresponding N,N- dibutylaminophenyl compound. Hydrolysis with sodium hydroxide using i s the method of Example 1D affords the title compound. Example 169 frans.frans-1 -f2-N.N-Dibutylaminopyrimidin-4-vn-2-f4-methoxyphenvn-4-f 1.3- benzodioxol-5-vnpyrrolidine-3-carboxylic acid 20 2-(Dibutylamino)-4-chloropyrimidine is prepared from 2,4- dichloropyrimidine according to the method of Gershon, J. Heterocyclic Chem. 24: 205 (1987) and reacted with ethyl trans, frans-2-(4- methoxyphenyl)-4-(1 ,3-benzodioxol-5-yl)-pyrrolidine-3-carboxylate (the compound resulting from Example 6A) and diisoproplyethylamine in 25 dioxane with heating to give the intermediate ethyl ester, which is hydrolyzed with sodium hydroxide using the method of Example 1 D to the title compound. Examples 170-266 30 Using the procedures described in Examples 1 , 4, 5, 7, 8 and 9 and Scheme X, the following compounds can be prepared. Ex. No. Name 170 frans,frans-2-(4-Methoxyphenyl)-4-(1 ,3- benzodioxol-5-yl)-1 - (isopropylaminocarbonylmethyl)-pyrrolidine-3- carboxylic acid; frans,frans-2-(4-Methoxyphenyl)-4-(1 ,3- benzodioxol-5-yl)-1 -(ethylaminocarbonylmethyl)- pyrrolidine-3-carboxylic acid; frans,frans-2-(4-Methoxyphenyl)-4-(1 ,3- benzodioxol-5-yl)-1 -(1 - methylpropylaminocarbonylmethyI)-pyrrolidine-3- carboxylic acid; frans,frans-2-(4-Methoxyphenyl)-4-(1 ,3- benzodioxol-5-yl)-1 -(phenylaminocarbonylmethyl)- pyrrolidine-3-carboxylic acid; frans,frans-2-(4-Methoxyphenyl)-4-(1 ,3- benzodioxol-5-yl)-1 -(piperidinylcarbonylmethyl)- pyrrolidine-3-carboxylic acid; frans,frans-2-(4-Methoxyphenyl)-4-( 1 ,3- benzodioxol-5-yl)-1 -(1 - (propylaminocarbonyl)ethyl)-pyrrolidine-3- carboxylic acid; frans,frans-2-(4-Methoxyphenyl)-4-(1 ,3- benzodioxol-5-yl)-1 -(α- (propylaminocarbonyl)benzyl)-pyrrolidine-3- carboxylic acid; frans, frans-2-(4-Methoxyphenyl)-4-(1 ,3- benzodioxol-5-yl)- 1 -(bis- (propylaminocarbonyl)methyl)-pyrrolidine-3- carboxylic acid; frans,frans-2-(4-Methoxyphenyl)-4-( 1 ,3- benzodioxol-5-yl)-1 -(2- (propylaminocarbonyl)ethyl)-pyrrolidine-3- carboxylic acid; frans,frans-2-(4-Methoxyphenyl)-4-( 1 ,3- benzodioxol-5-yl)-1 -(propylaminosulfonylmethyl)- pyrrolidine-3-carboxylic acid; frans,frans-2-(4-Methoxyphenyl)-4-( 1 ,3- benzodioxol-5-yl)-1 -(2-phenethyl)-pyrrolidine-3- carboxylic acid; frans,frans-2-(4-Methoxyphenyl)-4-(1 ,3- benzodioxol-5-yl)-1 -(pentanoylmethyl)- pyrrolidine-3-carboxylic acid; frans,frans-2-(4-Methoxyphenyl)-4-(1 ,3- benzodioxol-5-yl)-1 -(benzoylmethyl)-pyrrolidine- 3-carboxylic acid; frans,frans-2-(4-Methoxyphenyl)-4-(1 ,3- benzodioxol-5-yl)-1 -(hexyl)-pyrrolidine-3- carboxylic acid; frans, frans-2-(4-Methoxyphenyl)-4-(1 ,3- benzodioxol-5-yl)-1 -(2-hexynyl)-pyrrolidine-3- carboxylic acid; trans, frans-2-(4-Methoxyphenyl)-4-(1 ,3- benzodioxol-5-yl)-1 -(propoxymethylcarbonyl- pyrrolidine-3-carboxylic acid; frans,fraπs-2-(4-Methoxyphenyl)-4-(1 ,3- benzodioxol-5-y I)- 1 -(phenyl acetyl )-pyrrolidine-3- carboxylic acid; frans,frans-2-(4-Methoxyphenyi)-4-(1 ,3- benzodioxol-5-yl)-1 -(anilinylcarbonyl)- pyrrolidine-3-carboxylic acid; frans,frans-2-(4-Methoxyphenyl)-4-(1 ,3- benzodioxol-5-yl)-1 -(2-acetylaminoethyl)- pyrrolidine-3-carboxylic acid; frans,frans-2-(4-Methoxyphenyl)-4-(1 ,3- benzodioxol-5-yl)-1 -(2-phenoxyethyl)-pyrrolidine- 3-carboxylic acid; frans, frans-2-(4-Methoxyphenyl)-4-(1 ,3- benzodioxol-5-yl)-1 -(2-benzodioxanylmethyl)- pyrrolidine-3-carboxylic acid; frans, frans-2-(4-Methoxyphenyl)-4-(1 ,3- benzodioxol-5-yl)-1 -(2-tetrahydrofuranylmethyl)- pyrrolidine-3-carboxylic acid; frans, frans-2-(4-Methoxyphenyl)-4-(1 ,3- benzodioxol-5-yl)-1 -(2- (propylaminocarbonylamino)ethenyl)-pyrrolidine- 3-carboxylic acid; frans,frans-2-(4-Methoxyphenyl)-4-(1 ,3- benzodioxol-5-yl)-1 -(2- (propylaminocarbonylamino)ethyl)-pyrrolidine-3- carboxylic acid; frans,frans-2-(4-Methoxyphenyl)-4-(1 ,3- benzodioxol-5-yl)-1 -(3-oxohex-1 -enyl)- pyrrolidine-3-carboxylic acid; frans,frans-2-(2,4-Dimethoxyphenyl)-4-(1 ,3- benzodioxol-5-yl)-1 -(propylaminocarbonylmethyl)- pyrrolidine-3-carboxylic acid; trans, frans-2-(2-Carboxy-4-methoxyphenyl)-4- (1 ,3-benzodioxol-5-yl)-1 - (propylaminocarbonylmethyl)-pyrrolidine-3- carboxylic acid; trans, frans-2-(2-Aminocarbonyl-4- methoxyphenyl)-4-(1 ,3-benzodioxol-5-yl)-1 - (propylaminocarbonylmethyl)-pyrrolidine-3- carboxylic acid; trans, frans-2-(2-Methanesulfonamido-4- methoxyphenyl)-4-(1 ,3-benzodioxol-5-yl)-1 - (propylaminocarbonylmethyl)-pyrrolidine-3- carboxylic acid; trans, fraπs-2-(2-Aminocarbonylmethoxy-4- methoxyphenyl)-4-(1 ,3-benzodioxol-5-yl)-1 - (propylaminocarbonylmethyl)-pyrrolidine-3- carboxylic acid; trans, frans-2-(2-Methoxyethoxy-4- methoxyphenyl)-4-(1 ,3-benzodioxol-5-yl)-1 - (propylaminocarbonylmethyl)-pyrrolidine-3- carboxylic acid; trans, frans-2-(2-Carboxy methoxy-4- methoxyphenyl)-4-(1 ,3-benzodioxol-5-yl)-1 - (propylaminocarbonylmethyl)-pyrrolidine-3- carboxylic acid; 202 frans, frans-2-(4-Methoxy-2- tetrazolylmethoxyphenyl)-4-(1 ,3-benzodioxol-5- yl)-1 -(propylaminocarbonylmethyl)-pyrrolidine-3- carboxylic acid; 203 trans, frans-2-(2-Allyloxy-4-methoxyphenyl)-4- ( 1 ,3-benzodioxol-5-yl)-1 - (propylaminocarbonylmethyl)-pyrrolidine-3- carboxylic acid; 204 trans.trans 2,4-Bis(4-methoxyphenyl)-1- (propylaminocarbonylmethyl)-pyrrolidine-3- carboxylic acid; 205 trans.trans 2,4-Bis(1 ,3-benzodioxol-5-yl)-1 - (propylaminocarbonylmethyl)-pyrrolidine-3- carboxylic acid; 206 frans,frans-2-(4-Methoxyphenyl)-4-(1 ,3- benzodioxol-5-yl)- 1 -(N-methyl-N- propylaminocarbonylmethyl)-pyrrolidine-3- carboxylic acid; 207 frans,frans-2-(4-Methoxyphenyl)-4-( 1 ,3- benzodioxole-5-yl)-1 -(N-methyl-N- butylaminocarbonyI)-pyrrolidine-3-carboxylic acid; 208 frans,frans-2-(4-Methoxyphenyl)-4-( 1 ,3- benzodioxol-5-yl)-1 -(N-methyl-N-(4- methoxyphenyl)aminocarbonyl)-3-pyrrolidine-3- carboxylic acid; 209 frans, rans-2-(4-Methoxyphenyl)-4-( 1 ,3- benzodioxol-5-yl)-1 -(N-methyl-N- phenylaminocarbonyl)-pyrrolidine-3-carboxylic acid; 21 0 frans,frans-2-(4-Methoxyphenyl)-4-(1 ,3- benzodioxol-5-yl)-1 -(N-methyl-N- allylaminocarbonylmethyl)-pyrrolidine-3- carboxylic acid; 21 1 frans,frans-2-(4-Methoxyphenyl)-4-(1 ,3- benzodioxol-5-yl)-1 -(N-methyl-N-(n- butyl)aminocarbonylmethyl)-pyrrolidine-3- carboxylic acid; frans,frans-2-(4-Methoxyphenyl)-4-(1 ,3- benzodioxol-5-yl)-1 -(N-methyl-N- isobutylaminocarbonylmethyl)-pyrrolidine-3- carboxylic acid; frans,frans-2-(4-Methoxyphenyl)-4-( 1 ,3- benzodioxol-5-yl)-1 -(N-methyl-N- cyclopentylaminocarbonylmethyl)-pyrrolidine-3- carboxylic acid; frans,frans-2-(4-Methoxyphenyl)-4-( 1 ,3- benzodioxol-5-yl)-1 -(N-methyl-N-(2- methoxyethyl)aminocarbonyl)-pyrrolidine-3- carboxylic acid; trans, frans-2-(4-Methoxyphenyl)-4-( 1 ,3- benzodioxol-5-yl)-1 -(N-methyl-N- butoxyethylaminocarbonyl)-pyrrolidine-3- carboxylic acid; frans,frans-2-(1 ,3-Benzodioxol-5-yl)-4-(4- methoxyphenyl)-1 -(N-methyl-N- propylaminocarbonylmethyl)-pyrrolidine-3- carboxylic acid; frans,frans-2-(4-Methoxyphenyl)-4-( 1 ,4- benzodioxan-6-yl)-1 -(N-methyl-N- propylaminocarbonylmethyl)-pyrrolidine-3- carboxylic acid; frans,frans-2-(4-Methoxyphenyl)-4-( 1 ,3- benzodioxol-5-yl)- 1 -(N-methyl-N- isopropylaminocarbonylmethyl)-pyrrolidine-3- carboxylic acid; frans,frans-2-(4-Methoxyphenyl)-4-( 1 ,3- benzodioxol-5-yl)-1 -(N-methyl-N- ethylaminocarbonylmethyl)-pyrrolidine-3- carboxylic acid; frans,frans-2-(4-Methoxyphenyl)-4-( 1 ,3- benzodioxol-5-yl)-1 -(N-methyl-N-( 1 - methylpropyl)aminocarbonylmethyl)-pyrrolidine-3- carboxylic acid; 221 frans,frans-2-(4-Methoxyphenyl)-4-( 1 ,3- benzodioxol-5-yl)-1 -(N-methyl-N- phenylaminocarbonylmethyl)-pyrrolidine-3- carboxylic acid; 222 frans,frans-2-(4-Methoxyphenyl)-4-( 1 ,3- benzodioxol-5-yl)-1 -(1 -(N-methyl-N- propylaminocarbonyl)ethyl)-pyrrolidine-3- carboxylic acid; 223 frans,frans-2-(4-Methoxyphenyl)-4-(1 ,3- benzodioxol-5-yl)-1 -(α-(N-methyl-N- propylaminocarbonyl)benzyl)-pyrrolidine-3- carboxylic acid; 224 frans,frans-2-(4-Methoxyphenyl)-4-(1 ,3- benzodioxol-5-yl)-1 -(N-ethyl-N- propylaminocarbonylmethyl)-pyrrolidine-3- carboxylic acid; 225 frans,frans-2-(4-Methoxyphenyl)-4-( 1 ,3- benzodioxole-5-yl)-1 -(N-ethyl-N- butylaminocarbonyl)-pyrrolidine-3-carboxylic acid; 226 frans,frans-2-(4-Methoxyphenyl)-4-( 1 ,3- benzodioxol-5-yl)- 1 -(N-ethyl-N-(4- methoxyphenyl)aminocarbonyl)-3-pyrrolidine-3- carboxylic acid; 227 frans,frans-2-(4-Methoxyphenyl)-4-( 1 ,3- benzodioxol-5-yl)-1 -(N-ethyl-N- phenylaminocarbonyl)-pyrrolidine-3-carboxylic acid; 228 frans,frans-2-(4-Methoxyphenyl)-4-(1 ,3- benzodioxol-5-yl)-1 -(N-ethyl-N- allylaminocarbonylmethyl)-pyrrolidine-3- carboxylic acid; 229 frans,frans-2-(4-Methoxyphenyl)-4-( 1 ,3- benzodioxol-5-yl)-1 -(N-ethyl-N- isobutylaminocarbonylmethyl)-pyrrolidine-3- carboxylic acid; 230 frans,frans-2-(4-Methoxyphenyl)-4-( 1 ,3- benzodioxol-5-yl)-1 -(N-ethyl-N- cyclopentylaminocarbonylmethyl)-pyrrolidine-3- carboxylic acid; 231 frans,frans-2-(4-Methoxyphenyl)-4-( 1 ,3- benzodioxol-5-yl)-1 -(N-ethyl-N- methoxyethylaminocarbonyl)-pyrrolidine-3- carboxylic acid; 232 frans,frans-2-(4-Methoxyphenyl)-4-( 1 ,3- benzodioxol-5-yl)-1 -(N-ethyl-N- butoxyethylaminocarbonyl)-pyrrolidine-3- carboxylic acid; 233 trans, trans-2-( \ ,3-Benzodioxol-5-yl)-4-(4- methoxyphenyi)-1 -(N-ethyl-N- propylaminocarbonylmethyl)-pyrrolidine-3- carboxylic acid; 234 frans,frans-2-(4-Methoxyphenyl)-4-( 1 ,4- benzodioxan-6-yl)-1 -(N-ethyl-N- propylaminocarbonylmethyl)-pyrrolidine-3- carboxylic acid; 235 frans,frans-2-(4-Methoxyphenyl)-4-( 1 ,3- benzodioxol-5-yl)-1 -(N-ethyl-N- isopropylaminocarbonylmethyl)-pyrrolidine-3- carboxylic acid; 236 frans,frans-2-(4-Methoxyphenyl)-4-( 1 ,3- benzodioxol-5-yl)-1 -(N,N- diethylaminocarbonylmethyl)-pyrrolidine-3- carboxylic acid; 237 frans,frans-2-(4-Methoxyphenyl)-4-( 1 ,3- benzodioxol-5-yl)- 1 -(N-ethyl-N-( 1 - methylpropyl)aminocarbonylmethyl)-pyrrolidine-3- carboxylic acid; 238 frans,frans-2-(4-Methoxyphenyl)-4-( 1 ,3- benzodioxol-5-yl)-1 -(N-ethyl-N- phenylaminocarbonylmethyl)-pyrrolidine-3- carboxylic acid; 239 frans,frans-2-(4-Methoxyphenyl)-4-( 1 ,3- benzodioxol-5-yl)-1 -( 1 -(N-ethyl-N- propylaminocarbonyl)ethyl)-pyrrolidine-3- carboxylic acid; 240 frans,frans-2-(4-Methoxyphenyl)-4-( 1 ,3- benzodioxol-5-yl)-1 -(α-(N-ethyl-N- propylaminocarbonyl)benzyl)-pyrrolidine-3- carboxylic acid; 241 trans, frans-2-(4-Methoxyphenyl)-4-(1 , 3- benzodioxol-5-yl)-1 -(N-methyl-N- isobutylaminocarbonylmethyl)-pyrrolidine-3- carboxylic acid; 242 frans,frans-2-(4-Methoxyphenyl)-4-(1 ,3- benzodioxol-5-yl)- 1 -(N-methyl-N- cyclohexylaminocarbonylmethyl)-pyrrolidine-3- carboxylic acid; 243 frans,frans-2-(4-Methoxyphenyl)-4-( 1 ,3- benzodioxol-5-yl)-1 -(N,N- dipropylaminocarbonylmethyl)-pyrrolidine-3- carboxylic acid; 244 frans, frans-2-(4-Methoxyphenyl)-4-(1 ,3- benzodioxol-5-yl)- 1 -(isobutyloxyethyl)- pyrrolidine-3-carboxylic acid; 245 frans, frans-2-(4-Methoxyphenyl)-4-( 1 ,3- benzodioxol-5-yl)-1 -(butylsulfonyl)-pyrrolidine- 3-carboxylic acid; 246 frans,frans-2-(4-Methoxyphenyl)-4-( 1 ,3- benzodioxol-5-yl)- 1 - (isopropylsulfonylaminoethyl)-pyrrolidine-3- carboxylic acid; 247 frans, rans-2-(4-Methoxyphenyl)-4-( 1 ,3- benzodioxol-5-yl)- 1 - (ethoxymethylcarbonylmethyl)-pyrrolidine-3- carboxylic acid; 248 frans,frans-2-(4-Methoxyphenyl)-4-(1 ,3- benzodioxol-5-yl)-1 -(2-ethylbutyrylmethyl)- pyrrolidine-3-carboxylic acid; 249 frans,frans-2-(4-Methoxyphenyl)-4-( 1 ,3- benzodioxol-5-yl)-1 -(N-methyl-N-(3,4- dimethoxybenzyl)aminocarbonylmethyl)- pyrrolidine-3-carboxylic acid; 250 frans,frans-2-(4-Methoxyphenyl)-4-(1 ,3- benzodioxol-5-yl)-1 -[(1 R)-1 -(N-methyl-N- propylaminocarbonyl)butyl]-pyrrolidine-3- carboxylic acid; 251 frans,frans-2-(4-Methoxyphenyl)-4-( 1 ,3- benzodioxol-5-yl)- 1 -[(1 S)-1 -(N-methyl-N- propylaminocarbonyl)butyl]-pyrrolidine-3- carboxylic acid; 252 frans,frans-2-(4-Methoxyphenyl)-4-( 1 ,3- benzodioxol-5-yl)-1 -(3-isopropoxypropyl)- pyrrolidine-3-carboxylic acid; 253 frans,frans-2-(4-Methoxyρhenyl)-4-( 1 ,3- benzodioxol-5-yl)-1 -(5-methylhexyl)-pyrrolidine- 3-carboxyiic acid; 254 frans,frans-2-(4-Methoxyphenyl)-4-( 1 ,3- benzodioxol-5-yl)-1 -(5-methyl-2-hexenyl)- pyrrolidine-3-carboxylic acid; 255 frans,frans-2-(4-Methoxyphenyl)-4-( 1 ,3- benzodioxol-5-yl)-1 -(5-methyl-4-hexenyl)- pyrrolidine-3-carboxylic acid; 256 frans,frans-2-(4-Methoxyphenyl)-4-( 1 ,3- benzodioxol-5-yl)- 1 -(3,5-dimethyl-2-hexenyl)- pyrrolidine-3-carboxylic acid; 257 frans,frans-2-(4-Methoxyphenyl)-4-( 1 ,3- benzodioxol-5-yl)-1 -(2-(N-methyl-N- isobutyrylamino)ethyl)-pyrrolidine-3-carboxylic acid; 258 frans, frans-2-(4-Methoxyphenyl)-4-(1 ,3- benzodioxol-5-yl)-1 -(N-methyl-N-(2,2- dimethylpropyl)aminocarbonylmethyl)-pyrrolidine- 3-carboxylic acid; 259 frans,frans-2-(4-Methoxyphenyl)-4-(1 ,3- benzodioxol-5-yl)-1 -(N-ethyl-N- butylaminocarbonylmethyl)-pyrrolidine-3- carboxylic acid; 260 frans,frans-2-(4-Methoxyphenyl)-4-(1 ,3- benzodioxol-5-yl)-1 -(N-methyl-N- benzylaminocarbonylmethyl)-pyrrolidine-3- carboxylic acid; 262 frans,frans-2-(4-Methoxyphenyl)-4-(5-indanyl)-1 - (N-methyl-N-propylaminocarbonylmethyl)- pyrrolidine-3-carboxylic acid; 262 trans, frans-2-(4-Methoxyphenyl)-4-(2, 3- dihydrobenzofuran-5-yl)-1 -(N-methyl-N- propylaminocarbonylmethyl)-pyrrolidine-3- carboxylic acid; 263 frans,frans-2-(4-Methoxyphenyl)-4-(1 - methylindol-5-yl)- 1 -(N-methyl-N- propylaminocarbonylmethyl)-pyrrolidine-3- carboxylic acid; 264 frans,frans-2-(4-Methoxyphenyl)-4-(2-naphthyl)- l -(N-methyl-N-propylaminocarbonylmethyl)- pyrrolidine-3-carboxylic acid; 265 frans,frans-2-(4-Methoxyphenyl)-4-( 1 ,2- dimethoxy-4-phenyl)-1 -(N-methyl-N- propylaminocarbonylmethyl)-pyrrolidine-3- carboxylic acid; 266 trans, frans-2-(4-Methoxyphenyl)-4-(1 -methoxy-3- phenyl)-1 -(N-methyl-N- propylaminocarbonylmethyl)-pyrrolidine-3- carboxylic acid; Examples 267-288 Following the procedures described in Example 1 and Scheme II, the following compounds can be prepared. 267 frans,frans-3-(4-Methoxyphenyl)-5-( 1 ,3- benzodioxol-5-yl)-1 -(propyiaminocarbonylmethyl)- piperidine-4-carboxylic acid; 268 frans,frans-3-(4-Methoxyphenyl)-5-(1 ,3- benzodioxol-5-yl)-1 -(aminocarbonylmethyl)- piperidine-4-carboxylic acid; 269 frans,frans-3-(4-Methoxyphenyl)-5-(1 ,3- benzodioxol-5-yl)-1 -(4-fluorobenzyl)-piperidine- 4-carboxylic acid; 270 frans,frans-3-(4-Methoxyphenyl)-5-( 1 ,3- benzodioxol-5-yl)-1 -(2-ethoxyethyl)-piperidine-4- carboxylic acid; 271 frans,frans-3-(4-Methoxyphenyl)-5-( 1 ,3- benzodioxol-5-yl)-1 -(2-propoxyethyl)-piperidine- 4-carboxylic acid; 272 frans,frans-3-(4-Methoxyphenyl)-5-( 1 ,3- benzodioxol-5-yl)-1 -[2-(2-methoxyethoxy)ethyl]- piperidine-4-carboxylic acid; 273 fraπs,frans-3-(4-Methoxyphenyl)-5-( 1 ,3- benzodioxol-5-yl)-1 -[2-(2-pyridyl)ethyl]- piperidine-4-carboxylic acid; 274 frans,frans-3-(4-Methoxyphenyl)-5-( 1 ,3- benzodioxol-5-yl)-1 -(morpholin-4-ylcarbonyl)- piperidine-4-carboxylic acid; 275 frans,frans-3-(4-Methoxyphenyl)-5-(1 ,3- benzodioxole-5-yl)-1 -(butylaminocarbonyl)- piperidine-4-carboxylic acid; 276 frans, frans-3-(4-Methoxyphenyl)-5-( 1 ,3- benzodioxol-5-yl)-1 -(4- methoxyphenylaminocarbonyl)-3-piperidine-4- carboxylic acid; 277 frans,frans-3-(4-Methoxyphenyl)-5-( 1 ,3- benzodioxol-5-yl)-1 -acetylpiperidine-3-carboxylic acid; 278 frans,frans-3-(4-Methoxyphenyl)-5-(1 ,3- benzodioxol-5-yl)-1 -(2-furoyl)-piperidine-3- carboxylic acid; 27g frans,frans-3-(4-Methoxyphenyl)-5-(1 ,3- benzodioxol-5-yl)-1 -(phenylaminocarbonyl)- piperidine-4-carboxylic acid; 280 frans,frans-3-(4-Methoxyphenyl)-5-( 1 ,3- benzodioxol-5-yl)-1 -(allylaminocarbonylmethyl)- piperidine-4-carboxylic acid; 281 frans,frans-3-(4-Methoxyphenyl)-5-(1 ,3- benzodioxol-5-yl)- 1 -(n- butylaminocarbonylmethyl)-piperidine-4- carboxylic acid; 282 frans, frans-3-(4-Methoxyphenyl)-5-(1 ,3- benzodioxol-5-yl)-1 -(N-n-butyl-N- methylaminocarbonylmethyl)-piperidine-4- carboxylic acid; 283 frans,frans-3-(4-Methoxyphenyl)-5-( 1 ,3- benzodioxol-5-yl)-1 -(pyrrolidin-1 - ylcarbonylmethyl)-piperidine-4-carboxylic acid; 284 frans,frans-3-(4-Methoxyphenyl)-5-(1 ,3- benzodioxol-5-yl)-1 - (isobutylaminocarbonylmethyl)-piperidine-4- carboxylic acid; 285 frans,frans-3-(4-Methoxyphenyl)-5-(1 ,3- benzodioxol-5-yl)-1 - (cyclopentylaminocarbonylmethyl)-piperidine-4- carboxylic acid; 286 frans,frans-3-(4-Methoxyphenyl)-5-( 1 ,3- benzodioxol-5-yl)- 1 -(morpholin-4- ylaminocarbonylmethyl)-piperidine-4-carboxylic acid; 287 frans,frans-3-(4-Methoxyphenyl)-5-(1 ,3- benzodioxol-5-yl)-1 -(2-phenoxyethyl)-piperidine- 4-carboxylic acid; 288 frans,frans-3-(4-Methoxyphenyl)-5-(1 ,3- benzodioxol-5-yl)-1 -(methoxy ethylaminocarbonyl)- piperidine-4-carboxylic acid. Example 289 trans.trans- 2-f4-Methoxyphenyh-4-f 1 .3-benzodioxol-5-yπ-1 - f4- dibutylaminophenyh-pyrrolidine-3-carboxylic acid 4-Nitro-fluorobenzene, ethyl trans, frans-2-(4-methoxyphenyl)-4- 5 (1 ,3-benzodioxol-5-yl)-pyrrolidine-3-carboxylate (example 6A) and di- isopropyl ethylamine are heated in dioxane to give ethyl trans, trans-2- (4-methoxyphenyl)-4-(1 ,3-benzodioxol-5-yl)-1 -(4-nitrophenyl)- pyrrolidine-3-carboxylate. The nitro compound is hydrogenated to the corresponding aminophenyl compound. This is reacted with ι o butyraldehyde and sodium cyanoborohydride according to the method of Borch (J. Am Chem. Soc, 93, 2897, 1971) to give the corresponding N,N- dibutylaminophenyl compound, which is hydrolyzed with sodium hydroxide using the method of example 1D to give the title compound. 15 Example 290 trans, frans-2-f 4-Methoxy phenvh-4-f 1 ,3-benzodioxol-5-yπ-1 -f 2- dibutylamino-pyrimidine-4-yn-pyrrolidine-3-carboxylic acid 2-(Dibutylamino) 4-chloropyrimidine is prepared from 2-4- dichloropyrimidine according to the method of Gershon (J. Heterocyclic 20 Chem. 24, 205, 1987). This compound, ethyl frans,frans-2-(4- methoxyphenyl)-4-(1 ,3-benzodioxol-5-yl)-pyrrolidine-3-carboxylate (example 6A), and di-isopropyl ethylamine are heated in dioxane to give the intermediate ethyl ester, which is hydrolyzed with sodium hydroxide using the method of example 1D to give the title compound. 25 Example 291 frans.frans-2-f4-Methoxyphenvn-4-f1.3-benzodioxol-5-yn-1-fN-butyl-N- phenylaminocarbonylmethvn-pyrrolidine-3-carboxylic acid The title compound was prepared according to the general so procedure of Example 1. 1 H NMR (CD 3 OD) : δ 0.87 (t,3H,J=8); 1.2-1.35 (m,2H); 1.35-1.5 (m,2H); 2.78 (m, 2H); 3.10 (t,1 H, J=9); 3.26 (d,1H,J=15); 3.44 (dd,1H,J=5,10); 3.5-3.7 (m,3H); 3.77 (m,1H); 3.78 (s,3H); 5.93 (s,2H); 6.7-6.9 (m,4H); 7.0-7.2 (m,5H); 7.4 (m,3H). MS (DCI/NH 3 ): m/e 531 (M+H)+. Anal calcd for C 31 H 34 N 2 0 6 : C, 70.17; H, 6.46; N, 5.28. 35 Found: C.70.36; H, 6.52; N, 4.99. Example 292 Sodium frans. frans-2-f4-Methoxyphenvn-4-f1.3-benzodioxol-5-yn-1 -fN.N- /pL/f /arn nocarpon mefή )-pyrrolidine-3-carboxylate 5 Example 292A Ethyl 3-f4-methoxvphenyπ-3-oxopropionate Simultaneous reactions were run in both a 65-L reactor and a 35- L reactor that share the same reflux system. A nitrogen atmosphere was maintained in both. 4.0 kg (100 moles) of 60% sodium hydride in ι o mineral oil and 32 L toluene were charged into the ambient temperature reactors. The mixture was agitated for 5 minutes and allowed to settle. 20 L of the toluene solution was aspirated. 28 L of toluene was added, agitated for 5 minutes, allowed to settle and 28 L of the toluene solution was aspirated. 68 L of toluene and 8.4 L (69.7 15 moles) diethyl carbonate were added. The agitation was begun and the flow of Syltherm (Note 4) in reactor jackets was initiated. A solution of 5.0 kg (33.3 moles) 4-methoxyacetophenone in 12 L toluene was added over 20 minutes. When additions were complete, the jacket temperaturewas reduced to 10° C and stirring continued for 16 hours. 20 A solution of 6.7 L (117 moles) glacial acetic acid in 23 L deionized water was fed at the same rate that was previously used for the acetophenone solution. When addition was complete, agitation was stopped and the layers separated. The aqueous layer was washed once with 13 L toluene. The combined organic layers were washed twice 25 with 6.7 L portions of 7% (w:w) aqueous sodium bicarbonate. The toluene solution was washed once with 6.7 L of 23% (w:w) aqueous sodium chloride . The organic solution was dried over 10 kg sodium sulfate, filtered, and the solvent removed on the rotary evaporator to provide the desired product. 30 Example 292B 3.4- Methylenedioxy- 1 -f2-nitroethenyh-benzene In a 45-L cryogenic reactor with a contoured, anchor stirrer was dissolved 5.537 kg (36.9 moles) piperonal in 9 L methanol and 2.252 kg 35 (36.9 moles) nitromethane at 15°-20° C. The jacket temperature was set to -5° C and the reaction solution cooled to a temperature of +3.5° C. A 21 ° C solution of 3.10 kg (38.8 moles) 50% (w:w) aquous sodium hydroxide diluted with 3.7 L water was pumped in. The reaction temperature was maintained between 10°-15° C. When addition was complete, the jacket temperature was reset to 1 ° C and stirring continued for 30 minutes. A mixture of 7 kg ice in 19 L water was 5 added to dissolve most of the solid. The reaction mixture was filtered through canvas and then a 27R10SV Honeycomb filter. The filtered solution was metered into a 21° C mixture of 7.4 L concentrated hydrochloric acid in 11.1 L deionized water. The final reaction temperature was 26° C. The resulting product was centrifuged and ι o washed until the wash pH rose to at least 6 (by pH indicating paper). The crude product was dissolved in 92 L dichloromethane and the layers separated. The aqueous layer was washed once with 8 L dichloromethane. The combined organics were dried over 1.32 kg magnesium sulfate and filtered through Whatman #1 paper. The volume i s was reduced to 20% and the solution cooled to 4° C. Filtration through Whatman #1 paper, followed by ambient temperature drying in vacuo with an air leak afforded 1.584 kg (22%) of a first crop Concentration of the MLS to 25% followed by similar cooling, filtration, and drying afforded 0.262 kg (4%) of a second crop. The yellow product darkened 20 on standing in light and air. Example 292C Ethyl 2-f4-methoxybenzovn-3-f 1.3-benzodioxol-5-vh-4-nitro- butanoate 25 Into a 45-L stirred reactor at ambient temperature were charged 5.819 kg (30.1 moles) 3,4-methylenedioxy-1 -(2-nitroethenyl)-benzene and 24 L ethyl acetate . A solution of 5.355 kg (24.1 moles) ethyl 3-(4- methoxyphenyl)-3-oxopropionate in 16 L ethyl acetate was added. 280 g (275 ml, 1.84 moles) of 1 ,8-diaza-bicyclo[5.4.0]undec-7-ene in four 30 equal portions was added over a 2.5 hour period. The reaction mixture was filtered through dicalite and the resulting filtered solution was used in the next step without any further purification. Example 292D Ethyl 2-f4-methoxvphenvh-4-f1 .3-benzodioxol-5-vn-4.5-dihvdrp-3H- pyrrς>ι-3-carbQxylate The product of Example 292C (1316 ml solution consisting of 300 5 g Ethyl 2-(4-methoxybenzoyl)-3-(3,4-methylenedioxyphenyl)-4 nitrobutanoate in ethyl acetate) was added to a glass reactor containing RaNi # 28 (300 g). The reaction mixture was shaken under a hydrogen environment of 4 atm at room temperature for 18 hoursand filtered through a nylon 0.20 micron 47 mm millipore. ι o The filtrate was concentrated to 1.4 kg of dark solution and purified by normal phase silica gel chromatography eluting with 85:15, hexanes: ethyl acetate. The pure fractions were combined and concentrated (as above) until crystals formed. The solution was cooled to 0° C and filtered. The solid was washed with 2 L of 85:15, hexane: 15 ethyl acetate (0° C). The solids were dried in vacuo at 50° C to a constant weight of 193.4 g (21% yield, melting point 80-81° C) of the title compound. A further 200 g (23% yield) of product was obtained from the mother liquors. 20 Example 292 E Ethyl 2-f4-methoxyphenvπ-4-f 1.3-benzodioxol-5-vπ-pyrrolidine 3- carboxvlate Into a 12-L flask equipped with magnetic stirring, addition funnel, temperature probe, and nitrogen inlet was charged 0.460 kg 25 ethyl 2-(4-methoxyphenyl)-4-(3,4-methylenedioxyphenyl)-4,5-dihydro- 3H -pyrrole-3-carboxylate (1.25 mol). The reaction vessel was degassed with nitrogen. Absolute 3.7 L ethanol and 1.12 L of THF were added. 31 mg bromocresol green and 94.26g sodium cyanoborohydride (1.5 mol) were added. A solution containing 400 mL absolute ethanol and 30 200 mL of 12 M HCl was then added. The reaction mixture was stirred for 30 minutes after addition was complete. After the starting material was consumed, 0.5 L of 7% aq. NaHC03 was added. The reaction mixture was concentrated and diluted with 5 L ethyl acetate. The organic layer was washed twice with 2 L of 7% aq. NaHC03 and once with 2.5 L of 35 23% aq. NaCI, the dried over 190g MgS04, filtered, and concentrated to give 447 g of the title compound as a thick yellow oil. Example 292 F Ethyl 2-f4-methoxypheny »-4-f 1 .3-benzodioxol-5-vn-1 -f N.N- dibutylaminocarbonyl methyl! pyrrolidine 3-carboxylate Into a 22-L flask equipped with overhead stirring, nitrogen inlet, 5 and condenser was charged ethyl 2-(4-methoxyphenyl)-4-(3,4- methylenedioxyphenyl)-pyrrolidine-3-carboxylate (2.223 kg, 6.02 mol). The reaction vessel was degassed with nitrogen. 13.2 L of acetonitrile, 3.66 L diisopropylethylamine (2.71 kg, 20.9 mol), and 1.567 kg dibutylamidomethyl bromide (6.26 mol) were added. The mixture was ιo refluxed at 78° C for 17 hrs. After the disappearance of starting material , the mixture was concentrated until crystals formed. The solid was filtered and washed with 4 L ethyl acetate (0° C). Concentrating of the filtrate was continued as above until all volatiles were removed. The residue was diluted with 40 L ethyl acetate and i s washed with 20 L deionized water. The organic layer was washed with 8 L of 23% aq. NaCI nad dried over 0.399 kg MgS04 and filtered. Concentration as above provided 3.112 kg (96 % yield) of the title compound as a dark oil. 20 Example 292G trans, frans-2-f 4-Methoxyphenvh-4-f 1.3-'benzodioxol-5-yh-pyrrolidine 3-carboxylate and preparation of trans.trans 2-f4-methoxyphenylV4- f3.4-dioxyphenylVpyrrolidine-3-carboxylic acid ethyl ester Into a 35-L reactor equipped with overhead stirring, nitrogen 25 inlet, and condenser was charged 3.112 kg ethyl 2-(4-methoxyphenyl)- 4-(3,4-methylenedioxyphenyl)-pyrrolidine 3-carboxylate (5.78 mol). 16.4 L of absolute ethanol was added and the reaction vessel was degassed with nitrogen. 0.115 kg of sodium ethoxide (1.69 mol) was added and the mixture was refluxed at 79° C for 1 hr. The mixture was 30 cooled to 15° C and 5 L of 7.6 M NaOH solution (38.1 mol) was added. The mixture was stirred at 15° C for 18 hrs. The solvent was evaporated and the residue dissolved in 15.8 L of deionized water and extracted with 28 L of ether. The ether solution was washed with 9.5 L deionized water. The aqueous wash was extracted with 3 L ether. 0.340 L of 12 M 35 HCl was added to the aqueous layer. The aqueous layer was extracted with 24 L of ethyl acetate. The organic layer was washed with 9 L of 23% aq. NaCI, dried with 0.298 kg MgSθ4 , filtered, and concentrated to give 2.132 kg of a dark oil. The oil was triturated with 18 L ether. The undesired solids were filtered and saved for later use. The mother liquors were concentrated to obtain 1.102 kg of light foam. The foam was dissolved in 5.5 L ethyl acetate with heating to 65° C. 14 L hexane was added slowly enough to keep the solution refluxing. The reaction mixture was cooled to 10° C and filtered. The crystals were washed with 2 L ether (0° C) and dried to constant weight in vacuo at 50° C to give 0.846 kg (43% yield, melting point 1 19-120) of crude product, which was further purified by normal phase silica gel chromatography. Example 292H Sodium frans.frans-2-f4-methoxv p henvn-4-( 1 .3-benzodioxol-5-yn-1 - fN.N-dibutvlaminocarbonvl methvH pyrrolidine 3-carboxylate Into a 20-L flask was charged trans, trans 2-(4-methoxy phenyl )- 4-(3,4-methyledioxyphenyl)-1 -(N,N-dibutylamino- carbonyl methyl) pyrrolidine 3-carboxylic acid (0.927 kg, 1.819 mol). A solution of 0.0720 kg NaOH (1.80 mol) dissolved in 4.65 L methanol was added. The reaction mixture was concentrated to an oil. Pentane (4 L) was added and the solution concentrated again. Pentane (4 L) was added again and concentration of this solution gave a light tan foam. The foam was dried in vacuo at 50° C to a constant weight of 0.937 kg (97% yield) of the title compound. Example 293 fraπs-frans-2-f4-Methoxyphenvn-4-f 1 .3-benzodioxol-5-vn-1 - fdecahvdroisoquinolin-2- carbonylmethvn-pyrrolidine-3-carboxylic acid- The title compound was prepared using the procedures described in example 1. NMR (CD 3 OD, 300 MHz) shows a mixture of isomers. MS (DCI/NH 3 ) m/z 521. Anal calcd for C30H36N2O6 . 1.3 TFA: C, 58.54; H, 6.62; N, 4.19 . Found: C, 58.34; H, 5.58; N, 4.00 . Example 294 frans-frans-2-f4-Methoxyphenyn-4-f 1 .3-benzodioxol-5-vπ- 1 -f3.3- dimethylpiperidinyl- carbonvlmethvn-pvrrolidine-3-carboxvlic acid. The title compound was prepared using the procedures described in example 1. NMR (CD3OD, 300 MHz) indicates presence of rotamers. δ 0.84 (s, 3H), 0.86 (s, 3H), 1.35-1.6 (m, 4H), 3.83 (s, 3H), 5.96 (s, 2H), 6.81 (d, 1 H, J=8), 6.90 (dd, 1 H, J=1,8). 7.01 (d, 2H, J=9), 7.03 (s, 1 H), 7.47 (d, 2H, J=9). MS (DCI/NH3) m/z 495. Anal calcd for C-28H34N2O6 . 1.4 TFA: C, 56.55; H, 5.45; N, 4.28 . Found: C, 56.52; H, 5.83; N, 4.26 . Example 295 frans-frans-2-f4-Methoxyphenvn-4-f 1 .3-benzodioxol-5-vn-1 - r .2-fN- propyl-N-iso-butoxycarbonylamino ethvn-pyrrolidine-3-carboxylic acid The title compound was prepared by the methods detailed in Example 61 , but substituting propylamine for methylamine in Example 61 B and isobutyl chloroformate for isobutyryl chloride in Example 61 C. The crude product was purified by trituration with 1 :1 diethyl ether/ hexane. The resulting solid was dissolved in CH3CN and water and lyophilized to give the product as a white solid. 1 H NMR (CDCI3, 300 MHz) δ 0.80 (t, 3H, J=7), 0.92 (m, 3H), 1.43 (h, 2H, J=7Hz), 1.7-1.9 (m, 1 H), 2.72 (m, 1 H), 2.90 (m, 2H), 3.10 (m, 2H), 3.25 (m, 2H), 3.40 (m, 1 H), 3.55 (m, 1 H), 3.62 (m, 1 H), 3.7-3.9 (m, 2H) 3.78 (s, 3H), 5.95 (s, 2H), 6.72 (d, 1 H, J= 8Hz), 6.82 (m, 3H), 7.00 (s, 1 H), 7.30 (d, 2H, J=8Hz). MS (DCI/NH3) m/e 527 (M+H) + . Anal calcd for C29H38N2O6 ■ 0.5 H 2 0: C, 65.03; H, 7.34; N, 5.23. Found: C, 65.13; H, 6.96; N, 4.95. Example 296 trans-trans-2-( 4- Methoxy phenvh-4-H .3-benzodioxol-5-yh-1 - [1 .2.3.4-tetrahydroisoquinolin-2- carbonylmethvπ-pyrrolidine-3- carboxylic acid. The title compound was prepared using the procedures described in example 1. NMR (CD3OD, 300 MHz) indicates presence of rotamers. δ 2.97 (m, 2H), 4.68 (s, 3H), 5.97 (s, 2H), 6.83 (d, 1 H, J=8), 6.9-7.0 (m, 3H), 7.03 (d, 1 H, J=2), 7.1-7.3 (m, 4H), 7.4-7.5 (m, 2H). MS (DCI/NH3) m/z 515. Example 297 frans-frans-2-f4-Methoxyphenvn-4-f 1 .3-benzodioxol-5-vπ-1 -f2-fN- proρyl-N-dimethylaminocarbonvlamino!ethyll-ρyrrolidine-3-carboxylic cid The title compound was prepared by the methods detailed in Example 61 , but substituting propylamine for methylamine in Example 61 B and dimethylcarbamyl chloride for isobutyryl chloride in Example 61 C. The crude product was purified by preparative HPLC (Vydac μC18) eluting with a 10-70% gradient of CH3CN in 0.1% TFA. The desired fractions were lyophilized to give the product as a white solid. 1 H NMR (CDCI3. 300 MHz) δ 0.70 (t, 3H, J=7), 1.28 (m, 2H), 2.75 (s. 3H), 2.82 (m, 2H), 3.1-3.45 (m, 4H), 3.70 (m, 1 H), 3.80 (s, 3H), 3.90 (m, 3H), 4.72 (m, 1 H), 5.95 (s, 2H), 6.75 (d, 1H, J= 8Hz), 6.87 (m, 3H), 7.05 (s, 1 H), 7.40 (d, 2H, J=8Hz). MS (DCI/NH3) m/e 498 (M+H) + . Anal calcd for C27H35N3O6 • 1.25 TFA: C, 55.35; H, 5.71 ; N, 6.56. Found: C, 55.41; H, 5.71 ; N, 6.41. Example 298 frans.frans-2-f4-Methoxvphenyπ-4-f 1 .3-benzodioxol-5-yn- 1 -f2-fN- propyl-N-f4-nitrobenzenesulfonyl)amino!ethyn-pyrrolidine-3- carboxylic acid Using the procedures described in Eample 66, the title compound was prepared as a yellow solid, m.p. 85-87°C. 1 H NMR (CDCI3, 300 MHz) δ 0.77 (t, J=7.5Hz, 3H), 1.38 (sextet, J=7.5Hz, 2H), 2.20-2.29 (m, 1 H), 2.57-2.66 (m, 1H), 2.82-3.15 (m, 4H), 3.22 (t, J=7.5Hz, 2H) 3.38 (dd, J=3Hz,J=9Hz, 1H), 3.4g-3.57 (m, 1 H), 3.5g (d, J=gHz, 1 H), 3.83 (s, 3H), 5.96 (s, 2H), 6.73 (d, J=8Hz, 1H), 6.82 (dd, J=1 Hz,J=8Hz, 1 H), 6.87 (d, J=9Hz, 2H), 6.98 (d, J=1 Hz, 1 H), 7.27 (d, J=9Hz, 2H), 7.82 (d, J=gHz, 2H), 8.23 (d, J=9Hz,2H). MS (DCI/NH3) m/e 612 (M+H)+- Example 299 frans. frans-2-f4-Methoxyρhenvh-4-f 1 .3-benzodioxol-5-yh-1 -f 2-f N- propyl-N-n-pentanesulfonylamino thvh-pyrrolidine-3-carboxylic acid Using the procedures described in Example 66, the title compound was prepared as a white solid, m.p. 59-61°C 1 H NMR (CDCI3, 300MHz) δ 0.79 (t, J=7.5Hz, 3H), 0.90 (t, J=6Hz, 3H), 1.26-1.32 (m, 4H), 1.43 (sextet, J=7.5Hz, 2H), 1.67-1.76 (m, 2H), 2.23-2.32 (m, 1 H), 2.70-3.08 (m, 7H), 3.15-3.32 (m,2H), 3.42 (dd, J=3Hz,J=9Hz, 1H), 3.52-3.57 (m, 1 H), 3.63 (d, J=9Hz, 1 H), 3.80 (s, 3H), 5.05 (s, 2H), 6.73 (d, J=7.5Hz, 1H), 6.83 (dd, J=1 Hz,J=7.5Hz, 1 H), 6.87(d, J=8Hz, 2H), 7.00 (d, J=1 Hz, 1 H), 7.32 (d, J=8Hz, 2H). MS (DCI/NH3) m/e 561 (M+H)+- Example 300 frans. frans-2-f 4-Methoxyphenvπ-4-f 1 .3-benzodioxol-5-y h-1 -f2-f N- ρroρyl-N-f4-trifluoromethoxybenzenesulfonvhamino!ethyh- pyrrolidine-3-carboxylic acid Using the procedures described in Example 66, the title compound was prepared as a white solid. m.p.122-124°C. 1 H NMR (CD30D, 300MHz) δ θ.75 (t, J=7.5Hz, 3H), 1.26-1.45 (m, 2H), 2.06-3.08 (m, 2H), 3.23 (bs, 2H), 3.35-3.45 (m, 2H), 3.52 (t, J=10Hz, 1 H), 3.81 (d, J=9Hz, 2H), 3.86 (s, 3H), 3.92 (t, J=9Hz, 1H), 4.63 (d, J=10Hz, 1 H), 5.97 (s, 2H), 6.82 (d, J=9Hz, 1 H), 6.93 (dd, J=3Hz,J=9Hz, 1 H), 7.06-7.08 (m, 3H), 7.46 (d, J=9Hz, 2H), 7.56 (d, J=gHz, 2H), 7.89 (d, J=9Hz, 2H). MS (DCI/NH3), m/e 651 (M+H) + . Example 301 frans. frans-2-f4-Methoxyphenyl )-4-f 1 .3-benzodioxol-5-yn-1 -(2-fN- propyl-N-f2-methyl-2-propenesulfonvhamino ethyπ-pyrrolidine-3- carboxylic acid Using the procedures described in Example 66, the title compound was prepared as a white solid, m.p. 69-71 °C. 1 H NMR (CDCI3, 300MHz) δ 0.79 (t, J=7.5Hz, 3H), 1.93 (sextet, J+7.5HZ, 2H), 1.92 (s, 3H), 2.25-2.35 (m, 1 H), 2.68-2.77 (m, 1 H), 2.85-3.28 (m, 7H), 3.40 (d, J=9Hz, 1 H), 3.52- 3.68 (m, 2H), 3.66 (d, J=9Hz, 1 H), 3.80 (s, 3H), 4.92 (s, 1 H), 5.07 (s, 1H), 5.97 (s, 2H), 6.74 (d, J=7Hz, 1H), 6.82-6.89 (m,3H), 7.01 (s,1 H), 7.33 (d, J=9Hz, 2H). MS (DCI/NH3), m/e 545 (M+H) + . Example 302 trans-trans-2-( 4-Methoxyphenyh-4-f 1 .3-benzodioxol-5-yh- 1 -\2- ethylpiperidinyl-carbonvlmethvM-pyrrolidine-3-carboxylic acid. The title compound was prepared using the procedures described in example 1. NMR (CD3OD, 300 MHz) shows a mixture of isomers. δ 0.75 (t, 3H, J=7), 1.4-1.7 (m, 8H), 3.84 (s, 3H), 5.96 (s, 2H), 6.83 (d, 1 H, J=8), 6.91 (d, 1 H, J=8), 7.0-7.1 (m, 3H), 7.52 (d, 2H, J=9). MS (DCI/NH3) m/z 495. Anal calcd for C28H34N2O6 . 1.6 TFA: C, 55.35; H, 5.30; N, 4.14 . Found: C, 55.26; H, 5.37; N, 4.01 . Example 303 frans. frans-2-f4-Methoxvphenyn-4-f 1 .3-benzodioxol-5-vn-1 -f2-fN- propyl-N-f2-methvlpropanesulfonvnamino thyn-pyrrolidine-3- carboxvlic acid Using the procedures described in Example 66, the title compound was prepared as a white solid, m.p. 72-73°C. 1 H NMR (CDCI3, 300 MHz) δ 0.82 (t, J=7.5Hz, 3H),1.04 (d, J=6Hz, 6H), 1.44(q, J=7.5Hz, 2H), 2.15-2.33 (m,2H), 2.57-2.75 (m, 2H), 2.84-3.08 (m, 3H), 3.12-3.21 (m, 1 H), 3.23- 3.45 (m, 1 H), 3.43 (d, J=11 Hz, 1 H), 3.55-3.62 (m, 1 H), 3.66 (d, J=9Hz, 1 H). 3.80 (s, 3H), 5.95 (s, 2H), 6.75 (d, J=9Hz, 1 H), 6.83 (dd, J=1 Hz,J=9Hz, 1 H), 6.87(d, J=9Hz, 2H), 7.02 (d, J=1Hz, 1 H), 7.33 (d, J=9Hz, 2H). MS (DCI/NH3) m/e 547 M+H) + . Example 304 trans. trans-2-( 4-Methoxyphenvh-4-f 1 .3-benzodioxol-5-y h-1 -f 2-(N- propyl-N-heptanesulfonylamino)ethyO-pyrrolidine-3-carboxylic acid Using the procedures described in Example 66, the title compound was prepared as a white solid. m.p.58-59°C. 1 H NMR (CDCI3, 300MHz) δ 0.80(t, J=7.5Hz, 3H), 0.88 (t, J=7Hz, 3H), 1.23-1.36 (m, 8H), 1.94 (q, J=7.5Hz, 2H), 1.71 (quintet, J=7Hz, 2H), 2.23-2.32 (m, 1H), 2.70-3.09(m, 7H), 3.13-3.32 (m,2H), 3.43(dd, J=3Hz,J=9Hz, 1 H), 3.52-3.58(m,1 H), 3.65(d, J=9Hz, 1 H), 3.80 (s, 3H), 5.96(s, 2H), 6.73 (d, J=7Hz, 1 H), 6.83 (dd, J=1 Hz, J=7Hz, 1 H), 6.87(d, J=9Hz, 2H), 7.01 (d, J=1 Hz, 1 H), 7.32(d, J=9Hz, 2H). MS (DCI/NH3) m/e 589 M+H) + . - 1 83 - Example 305 frans-frans-2-f4-Methoxvphenvn-4-f 1 .3-benzodioxol-5-vπ- 1 -r2-fN- ethyl-N-ethoxycarbonylamino!ethvn-Pvrrolidine-3-carboxylic acid Prepared by the methods detailed in Example 61 , but substituting ethylamine for methylamine in Example 61 B and ethyl chloroformate for isobutyryl chloride in Example 61 C. The crude product was purified by preparative HPLC (Vydac μC18) eluting with a 10-70% gradient of CH3CN in 0.1% TFA. The desired fractions were lyophilized to give the product as a white solid. 1 H NMR (CDCI3. 300 MHz) δ 0.90 (t, 3H, J=7), 1.22 (m, 3H), 3.0-3.2 (m, 4H), 3.42 (m, 2H), 3.78 (s, 3H), 3.82 (m, 4H), 4.10 (q, 2H, J=7Hz), 3.5 (br s, 1 H), 5.97 (dd, 2H, J=1 ,7Hz), 6.72 (d, 1H, J= 8Hz), 6.84 (m, 3H), 7.00 (s, 1 H), 7.42 (d, 2H, J=8Hz). MS (DCI/NH3) m/e 485 (M+H) + . Anal calcd for C26H32N2O7 • 1.2 TFA: C, 54.00; H, 5.30; N, 4.51. Found: C, 55.01 ; H, 5.36; N, 4.56. Example 306 frans. frans-2-f4-Methoxyphenyh-4-f 1 .3-benzodioxol-5-vn-1 -f2-f N- propyl-N-hexanesulfonylamino thyn-pvrrolidine-3-carboxylic acid Using the procedures described in Example 66, the title compound was prepared as a white solid. m.p.59-60°C. 1 H NMR (CDCI3, 300MHz) δ 0.80(t, J=7.5Hz,3H), 0.89(t, J=7Hz, 3H), 1.25-1.36(m, 6H), 1.53(sextet, J=7.5Hz, 2H), 1.72(quintet, J=7Hz, 2H), 2.23-2.32(m, 1 H), 2.72-3.08(m, 7H), 3.15-3.32(m, 2H), 3.43(d, J=9Hz, 1 H), 3.55-3.62(m, 1 H), 3.65 (d, J=10Hz, 1 H), 3.80(s, 3H), 5.96(s, 2H), 6.74(d, J=7.5Hz,1 H), 6.82(d, J=7.5Hz,1 H), 6.87(d, J=9Hz, 2H), 7.01(s,1H), 7.32(d, J=9Hz,2H). MS (DCI/NH3), m/e 575 (M+H) + . Example 307 frans-frans-2-f 4-Ethylphenyh-4-f 1 .3-benzodioxol-5-vn-1 -rN.N-difn- butvπaminocarbonylmethyll-pyrrolidine-3-carboxylic acid. The title compound was prepared using the procedures described in examples 1 and 49, substituting ethyl 4-ethylbenzoylacetate (prepared by the method of Krapcho et al., Org. Syn. 47, 20 (1967) starting with 4'-ethylacetophenone) in procedure 49B. NMR (CDCI3, 300 MHz) δ 7.31 (2H, d, J=8Hz), 7.16 (2H, d, J=8Hz), 7.03 (1 H, d, J=3Hz), 6.86 (1 H, dd, J=8&3Hz), 6.73 (1 H, d, J=9Hz), 5.94 (1 H, d, J=4Hz), 5.92 (1 H, d, J=4Hz), 3.77 (1 H, d, J=9Hz), 3.60 (1 H, m), 3.53-3.23 (5H, m), 3.13-2.90 (4H, m), 2.73 (1 H, d, J=14Hz), 2.62 (2H, q, J=9Hz), 1.45 (2H. m), 1.40- 1.10 (6H, m), 1.02 (2H, m), 0.87 (3H, t, J=7Hz), 0.78 (3H, t, J=7Hz). m/e (DCI, NH 3 ) 509 (MH + ) Anal.calc. for C30H40N2O5 C 70.84, H 7.93, N 5.51. Found C 70.80, H 7.85, N 5.25 . Example 308 frans-frans-2-f4-Methoxvphenyn-4-f 1 .3-benzodioxol-5-vh- 1 -r2-fN- propyl-N-(2-chloroethoxy carbonvlamino thyl1-pyrrolidine-3- carboxvlic acid Prepared by the methods detailed in Example 61 , but substituting propylamine for methylamine in Example 61 B and 2-chloroethyl chloroformate for isobutyryl chloride in Example 61 C. The crude product was purified by trituration with 1 :1 diethyl ether/ hexane. The resulting solid was dissolved in CH3CN and water and lyophilized to give the product as a white solid. 1 H NMR (CDCI3, 300 MHz) δ 0.80 (t, 3H, J=7), 1.22 (m, 3H), 2.15 (m, 1 H), 2.75 (m, 1H), 2.85 (m, 1 H), 3.1 (m, 2H), 3.25 (m, 2H), 3.5 (m, 3H), 3.65 (m, 2H), 3.80 (s, 3H), 4.18 (m, 1H), 4.30 (m, 1H), 5.98 (s, 2H), 6.72 (m, 1H), 6.82 (m, 3H), 7.00 (m, 1 H), 7.30(m, 2H). MS (DCI/NH3) m/e 533 (M+H) + . Anal calcd for C27H33N2O7CI: C, 60.84; H, 6.24; N, 5.26. Found: C, 60.48; H, 6.04; N, 5.10. Example 309 frans-frans-2-f2-Methoxyethyn-4-f 1 .3-benzodioxol-5-yn-1 -rN.N-difn- butyhamino carbonylmethyiypyrrolidine-3-carboxylic acid. The title compound was prepared using the procedures described in example 1 , substituting ethyl 5-methoxy-3-oxopentanoate for ethyl 4- methoxybenzoylacetate in Example 1A. The title compound is a yellow foam. 1 H NMR (CDCI3, 300 MHz) δ 0.91 (t, J=7Hz) and 0.95 (t, J=7Hz, 6H total), 1.28-1.41 (br m, 4H), 1.45-1.63 (br m, 4H), 2.00-2.20 (br m, 2H), 3.06 (br t, J=9Hz, 1 H), 3.30 (s) and 3.20-3.68 (br m, 11H total), 3.72-4.10 (br m, 4H), 5.92 (s, 2H), 6.72 (d, J=8.5Hz, 1H), 6.82 (dd, J=1.5, 8.5Hz, 1 H), 6.91 (d, J=1.5Hz, 1 H); MS (FAB) m/e 463 (M+H) + . Anal calcd for C25H38N2O5 H2O: C, 62.48; H, 8.39; N, 5.83. Found: C, 62.13; H, 8.15; N, 5.69. Examole 310 frans. frans-2-f4-Methoxyphenyn-4-f 1 .3-benzodioxol-5-yn- 1 -f2-f N- ethyl-N-n-pentanesulfonylamino thyn-pvrrolidine-3-carboxvlic acid Using the procedures described in Example 66, the title compound was prepared as a white solid. m.p.57-58°C. 1 H NMR (CDCI3, 300MHz) δ 0.89(t, J=7Hz, 3H), 1.06(t, J=7.5Hz, 3H), 1.26-1.37(m, 4H), 1.72(quintet, J=7.5Hz, 2H), 2.22-2.32(m,1 H), 2.71-2.96(m,5H), 3.08-3.30(m,4H), 3.95(d, J=9Hz, 1 H), 3.53-3.60(m. 1 H), 3.67(d, J=9Hz,1 H), 3.80(s, 1 H), 5.97(s, 2H), 6.73(d, J=gHz, 1 H), 6.82(d, J=gHz,1 H), 6.88(d, J=gHz, 2H),7.02(s,1 H), 7.33(d, J=9Hz, 2H). MS (CDI/NH3) m/e 547 (M+H) + . Example 31 1 frans-frans-2-f4-Methoxvphenvn-4-f 1 .3-benzodioxol-5-yπ-1 -rN.N- dicyclohexylamino carbonylmethvn-pyrrolidine-3-carboxylic acid. The title compound was prepared using the procedures described in example 1. NMR (CD 3 OD, 300 MHz) δ 1.0-2.0 (m, 20H), 3.0-3.1 (m, 2H), 3.80 (s, 3H), 5.95 (s, 2H), 6.75 (d, 1 H, J=8), 6.86 (dd, 1 H, J=2,8), 6.95 (d, 2H, J=9), 7.04 (d, 1 H, J=2), 7.38 (d, 2H, J=9). MS (DCI/NH3) m/z 563. Anal calcd for C33H42N2O6 . 0.5 H2O: C, 69.33; H, 7.58; N, 4.90 . Found: C, 69.42; H, 7.29; N, 4.78. Example 312 frans-frans-2-(4-Methoxyphenvπ-4-f 1 .3-benzodioxol-5-yl)- 1 -r2-f N- propyl-N-tert-butoxycarbonylamino^ethyll-pyrrolidine-3-carboxylic acid. The title compound was prepared using the procedures described in example 61 , substituting propylamine for aqueous methylamine in Example 61 B and di-tert-butyldicarbonate for isobutyryl chloride in Example 61 C. NMR (CD3OD, 300 MHz) suggests presence of rotamers δ 0.81 (t, 3H, J=7), 1.2-1.5 (m, 11 H), 3.78 (s, 3H), 5.92 (dd, 2H, J=1 ,2), 6.74 (d, 1 H, J=8), 6.84 (dd, 1 H, J=2,8), 6.92 (d, 2H, J=9), 6. 9 (bd s, 1 H), 7.35 (d, 2H, J=9). MS (DCI/NH3) m/z 527. Anal calcd for C29H38N2O7 : C, 66.14; H, 7.27; N, 5.32 . Found: C, 66..05; H, 7.36; N, 5.15. Exa pie 31 frans-frans-2-f4-Methoxv-3-fluorophenvn-4-f 1 .3-benzodioxol-5-yn- 1 -f N.N-difn-butvnamino carbonvlmethvn-Dvrrolidine-3-carboxylic acid. The title compound was prepared using the methods described in examples 1 and 43, using 4-methoxy-3-fluoro acetophenone in place of 4-methoxy acetophenone. m.p. 142-143 °C. NMR (CDCI3, 300 MHz) δ 0.82 (t, J=7Hz, 3H), 0.88 (t, J=7Hz, 3H), 1.03-1.50 (m, 8H), 2.82 (d, J=13Hz, 1 H), 2.90-3.13 (m, 4H), 3.20-3.50 (m, 3H), 3.39 (d, J=13H, 1 H), 3.55-3.65 (m, 1 H), 3.82 (d, J=10Hz, 1H), 3.87 (s, 3H), 5.91 (dd, J=2Hz, 4Hz, 2H), 6.72 (d, J=8Hz, 1 H), 6.83-6.91 (m, 2H), 6.99 (d, J=2Hz, 1 H), 7.06 (m, 2H). Anal calcd for C29H37N2O6F : C, 65.89; H, 7.06; N, 5.30 . Found: C, 65.82; H, 7.13; N, 5.29. Example 314 frans.frans-2-f PrøPvn-4-f1.3- benzodioxol-5-vn-1-f2-fN-propy[- pentanesulfonylaminotethvnpyrrolidine-3-carboxylic acid Example 31 A Prooyl pentanesulfonamide Pentane sulfonyl chloride (687 mg, 4.03 mmol) was dissolved in 5 mL CH2CI2 and added to an ice-cooled solution of n-propylamine (0.40 mL, 4.82 mmol) and ethyldiisopropylamine (0.85 mL, 4.88 mmol) in 5 mL CH2CI2 under a nitrogen atmosphere. The reaction was stirred at 0 °C for 30 min, then at 25 °C for 4 h. The solution was partitioned between 20 mL of 1.0 M aqeous NaHSθ4 and 25 mL CH2CI2. The organic phase was washed sequentially with 25 mL H2O and 25 mL brine, then dried (Na2Sθ4), filtered, and concentrated in vacuo to provide 739 mg (3.83 mmol, 95%) of the title compound as a white solid. TLC (25% EtOAc- hexane) Rf 0.23; 1 H NMR (CDCI3, 300 MHz) δ 0.92 (t, J=7Hz, 3H), 0.97 (t, J=7Hz, 3H), 1.28-1.50 (br m, 4H), 1.52-1.68 (m, 2H), 1.75-1.90 (br , 2H), 2.98-3.06 (m, 2H), 3.08 (q, J=6Hz, 2H), 4.10-4.23 (br m, 1H); MS (DCI/NH3) m/e 211 (M+NH 4 ) + . Example 3149B Ethyl trans.trans~4-h .3-benzodioxol-5-ylV1 -(2-bromoethylV2-propy|pyrrolidine-3- carboxvlate The title compound was prepared according the procedure of Example 61 A, substituting the compound of Example 94B for the pyrrolidine mixture. Example 314C Ethylfrans.frans-2-fPrQpvn-4-f1.3-benzodioxol-5-vn-1-f2-fN-prppyl- pentanesulfonvlaminotethvnpvrrolidine-3-carboxvlate A solution of the compound of Example 314A (6.6 mg, 34 μmol) in 0.1 mL 5 DMF was treated with sodium hydride (2 mg, 60% oil dispersion, 1.2 mg NaH, 50 μmol). The resulting mixture was stirred at room temperature for 15 min, then a solution of the compound of Example 189B (9.0 mg, 22 μmol) in 0.1 mL DMF was added, followed b y 0.5 mg of tetra-n-butylammonium iodide. The reaction was sealed under argon and stirred at 60 °C overnight. The reaction was concentrated o under high vacuum, and the residue was partitioned between 2 mL of saturated aqueous NaHCθ3, 1 mL water and 5 mL EtOAc. The organic phase was washed with 1 mL brine, dried by passing through a plug of Na2S04, and the filtrate concentrated in vacuo to an oil. The crude product was purified by preparative TLC (silica gel, 8 x 20 cm, 0.25 mm thickness, eluting with 20% EtOAc-hexane, providing 5 8.4 mg (73%) of the title compound as a wax. Example 314D frans.frans-4-f1.3-benzodioxol-5-yn-2-fPropyn-1-f2-fN-propyl- pentanesulfonylaminotethynpyrrolidine-3-carboxylic acid 0 The title compound was prepared according to the procedure of Example 71 C. 1H NMR (CDCI 3 , 300 MHz) δ 0.88-1.00 (m, 9H), 1.20-1.55 (br m, 6H), 1.55-1.68 (m, 3H), 1.70-1.85 (br m, 2H), 1.00-2.16 (br m, 2H), 2.84-3.26 (br m, 6H), 3.26-3.00 (br m, 6H), 5.05 (s, 2H), 6.76 (d, J=8Hz, 1H), 6.79 (m, 1H), 6.93 (br s, 1 H); HRMS (FAB) calcd for 5 C25H41 N2O6S (M+H) + 497.2685, found 497.2679. Example 315 frans. frans-2-f4-Methoxyphenyn-4-f 1 .3-benzodioxol-5-vπ- 1 -f2-fN- propyl-N-dimethylsulfamoylamino!ethvπ-pyrrolidine-3-carboxylic acid 0 Using the procedures described in Example 66, the title compound was preapred as a white solid. m.p.59-61°C. 1 H NMR (CDC13, 300MHz) δ 0.79 (t, J=7.5Hz, 3H), 1.45(sextet, J=7.5Hz, 2H), 2.22-2.31 (m,1 H), 2.65(s, 6H), 2.70-2.79(m, 1 H), 2.85-3.04(m, 4H), 3.09-3.32(m, 2H), 3.40(d, J=9Hz, 1H),3.55 (t, J=9Hz,1H), 3.65(d, J=9Hz,1 H), 3.81 (s, 3H), 5 5.96(s,2H), 6.75(d, J=gHz, 1H), 6.83(d, J=9Hz, 1 H), 6.88(d, J=9Hz, 2H), 7.02(s, 1H), 7.34(d, J=9Hz, 2H). MS (DCI/NH3) m/e534 (M+H) + . Example 316 frans-frans-2-f4-Methoxphenyh-4-f 1.3-benzodioxol-5-vh-1 -r2-fN- propvl-N-r4-methoxvphenvllsulfonvlamino!propyll-pyrrolidine-3- carboxylic acid 5 Example 316A Ethyl trans-trans and cis-trans 2-f4-Methoχyphenvn-4-M .3- benzodiox-5-vn -1 -(3-bromopropvn Pvrrolidine-3-carboxytate A 2:1 mixture of trans-trans and cis-trans ethyl 2-(4- o methoxyphenyl)-4-(1 ,3-benzodiox-5-yl) -pyrrolidine-3-carboxylate (4.00 g; prepared according to example 1C), 32 ml dibromopropane, and 200 mg sodium iodide, were heated at 100° for 1.25 hrs. The excess dibromopropane was removed in vacuo and the residue was dissolved in toluene. After shaking with potassium bicarbonate, the solution was 5 dried (Na2Sθ4) and the solution concentrated. The residue was chromatographed on silica gel eluting with 5:1 hexane:EtOAc. yielding 5.22 (98%) of the title compound. Example 316B 0 Ethyl trans-trans and cis-trans 2-f4-MethoxyphenvO-4-f 1 .3- benzodiox-5-yn -1 -f3-prppylaminopropvn pvrrolidine-3-carboxylate The compound described in Example 316A (5.22 g) was heated at 80° for 2 hrs.with 35 ml. ethanol, 2.5 g. propylamine and 35 mg. sodium iodide. The solvents were removed in vacuo. The residue was dissolved 5 in toluene, shaken with potassium bicarbonate solution and dried (Na2Sθ4). The soilution was concentated in vacuum to give 4.96 g of the title compound as an orange oil. This was used in the next step without purification. 0 Example 316C frans-frans-2-f4-Methoxphenyn-4-f 1 .3-benzodioxol-5-yh-1 -f2-f N- propyl-N-[4-methoxyphenyl1sulfonylamino!propyn-ρyrrolidine-3- carboxylic acid Using the method described in example 66, the compound prepared 5 in Example 316B was reacted with 4-methoxybenzenesulfonyl chloride in acetonitrile containing diisopropylethylamine. The resulting product was chromatographed on silica gel (30% EtOAc in hexane), and hydrolyzed to the title compound by the method of example 1D. NMR (CDCI3, 300 MHz) δ 0.83 (t, J=7Hz, 3H), 1.40-1.52 (m, 2H), 1.56-1.70 (m, 2H), 2.00-2.11 (m, 1 H), 2.40-2.51 (m, 1 H), 2.69-2.78 (m, 1 H), 2.84-3.03 (m, 4H), 3.19-3.34 (m, 2H), 3.48-3.59 (m, 2H), 3.80 (s, 3H), 3.86 (s, 3H), 5.95 (s, 2H), 6.74 (d, J=8Hz, 1 H), 6.85 (d, J=8Hz, 3H), 6.93 (d, J=8Hz, 2H), 7.02 (d, J=2Hz, 1H), 7.29 (d, J=8Hz, 2H), 7.69 (d, J=8Hz, 2H). Anal calcd for C32H38N2O8S : C, 62.93; H, 6.27; N, 4.59. Found: C, 62.97; H, 6.39; N, 4.45. Example 317 frans-frans-2-f4-Methoχphenvn-4-f 1 .3-benzodioxol-5-yn-1 -f2-(N- propyl-N-propylsulfonylamino)propyll-pyrrolidine-3-carboxylic acid Using the method described in example 66, the propylamino compound prepared in Example 316B was reacted with propanesulfonyl chloride in acetonitrile containing diisopropylethylamine. The resuling product was chromatographed on silica gel (30% EtOAc in hexane) and hydrolyzed to the title compound by the method of example 1D. NMR (CDCI3, 300 MHz) δ 0.85 (t, J=7Hz, 3H), 1.02 (t, J=7Hz, 3H), 1.47-1.60 (m, 2H), 1.65-1.85 (m, 4H), 2.04-2.16 (m, 1H), 2.42-2.57 (m, 1 H), 2.72- 3.11 (m, 5H), 3.25-3.41 (m, 2H), 3.50-3.62 (m, 2H), 3.80 (s, 3H), 5.85 (s, 2H), 6.72 (d, J=8Hz, 1 H), 6.80-6.90 (m, 3H), 7.02 (d, J=2Hz, 1H), 7.30 (d, J=9Hz, 2H). Anal calcd for C28H38N2O7S: C, 61.52; H, 7.01 ; N, 5.12 . Found: C, 61.32; H, 7.01 ; N, 5.01. Example 318 frans.frans-2-f3-Fluoro-4-methoxyphenvn-4-f 1 .3-benzodioxol-5- yh1 -f2-fN-propyl-N-pentanesulfonylamino!ethyn-pyrrolidine-3- carboxylic acid Using the procedures described in Example 313 and Example 66, the title compound was prepared as a white solid. m.p.66-68°C. 1 H NMR (CDCI3, 300MHz) δ 0.81(t,J=7.5Hz, 3H), 0.89(t, J=7Hz, 3H), 1.26-1.35(m, 4H), 1.45(sextet, J=7.5Hz, 2H), 1.68-1.76(m, 2H), 2.25-2.33(m, 1H), 2.72-2.92(m, 5H), 2.97-3.12(m, 2H), 3.16-3.33(m,2H), 3.43(dd, J=3Hz,J=9Hz,1 H), 3.53-3.60(m, 1 H), 3.66(d, J=10Hz, 1 H), 3.88(s, 3H), 5.95(s, 2H), 6.74(d, J=8Hz, 1 H), 6.82(dd, J=1 Hz,J=8Hz,1 H), 6.92(t, J=8Hz,1H), 6.97(d, J=1Hz, 1 H), 7.12(d, J=8Hz, 1 H), 7.18(dd, J=1 Hz,J=12Hz, 1 H). MS (DCI/NH3) m/e 579 (M+H) + . Example 319 frans-frans-2-f4-Pvridinyh-4-f 1 .3-benzodioxol-5-vn-1 -fN.N-difn- butynamino carbonvlmethvn-pvrrolidine-3-carboxvlic acid. The title compound was prepared using the methods described in examples 1 and 43, using methyl 3-oxo-3-(4-pyridyl)propanoate (J. Am. Chem. Soc. 1993, 1 15, 11705) in place of ethyl (4- methoxybenzoyl)acetate. m.p. 131-132 °C. NMR (CDCI 3 , 300 MHz) δ 0.82 (t, J+7Hz, 3H), 0.88 (t, J=7Hz, 3H), 1.05-1.50 (m, 8H), 2.90 (dd, J= 7Hz, 9Hz, 1H), 2.97 (d, J=13Hz, 1H), 3.00-3.25 (m, 4H), 3.32 (m, 1H), 3.39 (d, J=13Hz, 1 H), 3.45-3.52 (m, 1H), 3.67-3.78 (m, 1H), 4.10 (d, J=9Hz, 1 H), 5.92 (dd, J=2Hz, 4 Hz, 2H), 6.75 (d, J=9Hz, 1H), 6.90 (dd, J=9Hz, 2Hz, 1H), 7.02 (d, J=2Hz, 1H), 7.45 (d, J=8Hz, 2H), 8.50 (d, J=8Hz, 2H). Anal calcd for C27H35N3O5 : C, 67.34; H, 7.33; N, 8.73 . Found: C, 67.39; H, 7.45; N, 8.61. Example 32Q frans-frans-2-f4-Methoxyphenyh-4-f1 .3-benzodioxol-5-yh-1 -[2-fN- propyl-N-diethylaminocarbonylamino thvπ-pyrrolidine-3-carboxylic acid. The title compound was prepared using the procedures described in example 61 , substituting propylamine for aqueous methylamine in Example 61 B and diethylcarbamyl chloride for isobutyryl chloride in Example 61 C. NMR (CD3OD, 300 MHz) δ 0.74 (t, 3H, J=7), 1.09 (t, 6H, J=7), 1.33 (m, 2H), 3.17 (q, 4H, J=7), 3.78 (s, 3H), 4.04 (m, 1H), 5.93 (s, 2H), 6.86 (d, 1 H, J=8), 7.06 (dd, 1H, J=2,8), 6.94 (d, 2H, J=9), 7.04 (d, 1 H, J=2), 7.40 (d, 2H, J=9). MS (DCI/NH3) m/z 526. Anal calcd for C29H39N 3 O 6 • 0.1 TFA: C, 65.31 ; H, 7.34; N, 7.82 . Found: C, 65.33; H, 7.43; N, 8.14. Example 321 frans-frans-2-f4-Methoxvphenvn-4-f 1 .3-benzodioxol-5-yh-1 -r3.5- dimethylpiperidinyl- carbonylmethyll-pyrrolidine-3-carboxylic acid. The title compound was prepared using the procedures described in example 1. NMR (CD3OD, 300 MHz) shows mixture of isomers. δ 0.88 (d, 3H, J=7), 0.93 (d, 3H, J=7), 3.82 (s, 3H), 5.95 (s, 2H), 6.82 (d, 1H, J=8), 6.89 (dd, 1H, J=1 ,8), 7.00 d, 2H, J=9), 7.03 (m, 1 H), 7.47 (d, 2H, J=9). MS (DCI/NH3) m/z 4g5. Example 322 frans-frans-2-f4-Methoxv p henvn-4-π .3-benzodioxol-5-yn-1 -fN.N- difs-butvnamino carbonvlmethyn-pyrrolidine-3-carboxylic acid. The title compound was prepared using the procedures described in example 1. NMR (CD3OD, 300 MHz) suggests a mixture of isomers. δ 0.83 (t, 6H, J=8), 1.27 (d, 6H, J=7), 1.6 (m, 2H), 3.7g (s, 3H), 5.93 (s, 2H), 6.75 (d, 1H, J=8), 6.86 (d, 1H, J=8), 6.g4 (d, 2H, J=9), 7.03 (d, 1H, J=2), 7.35 (d, 2H, J=9). MS (DCI/NH3) m/z 511. Example 323 frans-frans-2-f4-Methoxyphenyn-4-f 1 .3-benzodioxol-5-yn-1 -fN-f2- Methylphenvh-N-butylamino carbonylmethyl]-pyrrolidine-3-carboxylic add- The title compound was prepared using the procedures described in example 1. MS (DCI/NH3) m/z 545. Anal calcd for C32H36N2O6 . 0.9 H 2 0: C, 68.53; H, 6.79; N, 4.99 . Found: C, 68.56; H, 6.62; N, 4.71. Example 324 frans-frans-2-f 4-Methoxyphenyh-4-f 1 .3-benzodioxol-5-yh- 1 -rN-f 3- Methylphenyh-N-butylamino carbonylmethyπ-pyrrolidine-3-carboxylic acid. The title compound was prepared using the procedures described in example 1. NMR (CD3OD, 300 MHz) d 0.88 (t, 3H, J=7), 1.2-1.5 (m, 4H), 2.31 (s, 3H), 2.8 (m, 2H), 3.14 (t, 1H, J=10), 3.3 (m, 1H), 3.44 (dd, 1H, J=5,10), 3.53 (m, 1 H), 3.60 (t, 2H, J=7), 3.79 (s, 3H), 3.82 (m, 1 H), 5.93 (s, 2H), 6.74 (d, 1H, J=8), 6.8-6.9 (m, 5H), 7.06 (d, 1 H, J=2), 7.09 (d, 2H, J=9), 7.18 (d, 1 H, J=7), 7.27 (t, 1 H, J=7). MS (DCI/NH 3 ) m/z 545. Anal calcd for C 3 2H3 6 N2O6 . 0.8 H 2 0: C, 68.75; H, 6.78; N, 5.01 . Found: C, 68.70; H, 6.67; N, 4.85. Example 325 frans.frans-4-f1.3-Benzodioxol-5-yn-2-fbenzyloxymethvn-1-ffN.N- dibutylaminocarbonvlmethvnpyrrolidine-3-carboxvlic acid 5 Example 325A Ethyl frans.frans-4-f1.3-Benzodioxol-5-vn-2-fbenzyloxymethvn-1-ffN - dibutvlaminocarbonvlmethvnpvrrolidine-3-carboxylate The procedures of Example 1A-1D were followed, substituting ethyl 4- benzyloxy-3-oxobutyrate for 4-methoxybenzoylacetate in Example 1A, to afford the o title compound as a colorless oil. TLC (30% EtOAc-hexane) Rf 0.18; 1 H NMR (CDCI 3 , 300 MHz) δ 0.88 (t, J=7Hz, 6H), 1.17 (t, J=7Hz, 3H), 1.20-1.34 (br m, 4H), 1.40-1.56 (br m, 3H), 2.85 (t, J=8Hz, 1 H), 2.98-3.30 (m, 5H), 3.39-3.60 (m, 3H), 3.64- 3.75 (m, 2H), 3.92 (d, J-14Hz, 1 H), 4.10 (two overlapping q, J=6.5Hz, 2H), 4.53 (s, 2H), 5.91 ( , 2H), 6.69 (d, J=9Hz, 1H), 6.77 (dd, J=1.5, 9Hz, 1H), 6.91 (d, J=1.5Hz, 5 1 H); MS (DCI/NH3) m/e 553 (M+H)+. Example 325B frans.frans-4-f1.3-Benzodioxol-5-vn-2-fbenzyloxymethvn-1-(fN.N- dibutylaminocarbonylmethvnpyrrolidine-3-carboxylic acid 0 The title compound was prepared according to the procedure of Example 71 C, as a colorless glass. TLC (5% MeOH-CH 2 CI 2 ) Rf 0.13; 1 H NMR (CDCI3, 300 MHz) δ 0.86 (t, J=7Hz), and 0.90 (t, J=7Hz, 6H total), 1.15-1.52 (br m, 8H), 2.96-3.35 (br m, 5H), 3.50-3.75 (br m, 2H), 3.80 (dd, J=3, 13Hz, 1H), 3.88-4.40 (br m, 6H), 4.45 (AB, 2H). 5.90 (s, 2H), 6.70 (d, J=8Hz, 1H), 6.84 (dd, J=1 ,8Hz, 1H), 6.93 (d, J=1Hz, 5 1H), 7.28-7.39 (m, 5H); MS (DCI/NH3) m/e 524 (M+H) + . Example 326 trans.trans-4-h .3-Benzodioxol-5-yn-2-fhvdroxymethvn-1 -ffN.N- dibutylaminocarbonylmethynpyrrolidine-3-carboxvlic acid 0 Example 326A Ethyl frans.frans-4-f1.3-Benzodioxol-5-yn-2-fhydroxymethyn-1-ffN.N- dibutylaminocarbonylmethynpyrrolidine-3-carboxvlate The resultant product from Example 325A (128 mg, 0.232 mmol) and 25 mg 5 of 20% Pd(OH)2 on charcoal in 7 mL EtOH was stirred under 1 atm hydrogen for 48 h. The mixture was filtered through a plug of celite, and the catalyst was washed with 2 x 10 mL EtOH, then the combined filtrate and washes were concentrated under reduced pressure to afford the crude product. Purification by flash chromatography (40%EtOAc-hexane) provided the title compound. Example 326B 5 frans frans-4-f1.3-Benzodioxol-5-vn-2-fhvdroxvmethvn-1-ffN.N- dibutylamino arbonynmethylpyrrolidine-3-carboxylic acid The title compound was prepared according to the procedure of Example 71C. ι o Example 327 frans.frans-4-f1.3-Benzodioxol-5-yn-2-fN-methylpro p enamid-3-yn-1-ffN.N- dibutylaminocarbonvlmethynpyrrolidine-3-carboxylic acid Example 327A 15 Ethyl trans.trans-4-π .3-Benzodioxol-5-vn-2-fformyn-1-ffN.N- dibutylaminocarbonylmethyl)pyrrolidine-3-carboxylate The title compound is made by selective oxidation (e.g. using the Swern oxidation with DMSO, oxalyl chloride, ethyldiisopropylamine or using the Dess- Martin periodinane) of the compound of Example 326A. 0 Example 327B Ethyl trans.trans-4- ■3-Benzodioxol-5-yn-2-fO-tert-butylpropenoat-3-yn-1 -ff N.N- dibutylaminocarbonylmethynpyrrolidine-3-carboxylate The title compound is produced by condensing the compound of Example 25 327A with tert-butyl triphenylphosphoranylidine acetate in CH2CI2 solution. Example 327C Ethyl trans.trans-4-h .3-Benzodioxol-5-yn-2-fpropenoic acid-3-yn-1 - fN.N- dibutylaminocarbonylmethynpyrrolidine-3-carboxylate 30 The title compound is produced by reacting the compound of Example 327B with trifluoacetic acid in CH2CI2 (1 :1). Example 327D Ethyl frans.frans-4-f1.3-Benzodioxol-5-yn-2-fN-methylpropenamid-3-yn-1-ffN N- dibutylaminocarbonylmethynpyrrolidine-3-carboxylate The title compound is produced by condensing the compound of Example 327C with methylamine hydrochloride in the presence of a carbodiimide (e.g. N- ethyl-N-(3-dimethylamino)propylcarbodiimide, DCC). Example 327E frans. frans-4-f1.3-Benzodioxol-5-vn-2-fN-methylpro p enamid-3-vn-1-ffN.N- dibutylaminocarbonylmethvnpyrrolidine-3-carboxylic acid The title compound is produced by reacting the compound of Example 327D with lithium hydroxide according to the procedure of Example 71 C. Example 328 frans. frans-4-f 1.3-Benzodioxol-5-vn-2-f1-hvdroxv-2-propen-3-yn-1-ffN.N- dibutylaminocarbonvlmethvnpvrrolidine-3-carboxvlic acid Example 328A Ethyl trans. frans--4-f 1.3-Benzodioxol-5-yn-2-f 1 -hvdroxy-2-propen-3-yn-1 -f fN.N- dibutylaminocarbonylmethynpyrrolidine-3-carboxylate The title compound is produced by reacting the compound of Example 327C with borane methyl sulfide complex. Example 328B frans.frans-4-f1.3-Benzodioxol-5-yn-2-f1 -hvdrox-2-propen-3-vn-1-ffN.N- dibutylaminocarbonylmethyl)pyrrolidine-3-carboxylic acid The title compound is produced by condensing the compound of Example 328A with lithium hydroxide according to the procedure of Example 71 C. Example 329 frans.frans-4-f1.3-Benzodioxol-5-yn-2-fN-benzylaminomethyn-1-ffN.N- dibutylaminocarbonylmethynpyrrolidine-3-carboxvlic acid Examole 329A Ethyl frans. frans--4-f1.3-Benzodioxol-5-yn-2-fN-benzvlaminomethyn-1-ffN.N- dibutylaminocarbonylmethvnpvrrolidine-3-carboxylate The title compound is produced by condensing the compound of Example 327A with benzylamine in the presence of sodium cyanoborohydride in ethanol. Example 329B frans.frans-4-f1.3-Benzodioxol-5-vn-2-fN-benzylaminomethyn-1-ffN N- riihtJtvlaminocarbonvlmethvnpvrrolidine-3-carboxylic acid The title compound is produced by reacting the compound of Example 329A with lithium hydroxide according to the procedure of Example 71 C. Example 330 frans.frans-4-(1 ■3-Benzodioxol-5-yn-2-fN-acetyl-N-benzylaminomethylV1-ffN.N- dibutylaminocarbonylmethvnpyrrolidine-3-carboxylic acid Example 330A Ethyl frans.frans-4-f1.3-Benzodioxol-5-vn-2-fN-acetyl-N-benzylaminomethyn-1- ffN.N-dibutylaminocarbonylmethynpyrrolidine-3-carboxylate The title compound is produced by reacting the compound of Example 3294A with acetic anhydride in the presence of pyridine or triethylamine. Example 330B frans. frans--4-f 1.3-Benzodioxol-5-yn-2-fN-acetyl-N-benzylaminomethvn-1-ffN.N- dibutvlaminocarbonylmethynpyrrolidine-3-carboxylic acid The title compound is produced by reacting the compound of Example 330A with lithium hydroxide according to the procedure of Example 71 C. Example 331 frans.frans--4-f1.3-Benzodioxol-5-yn-2-fethvnvn-1-ffN.N- dibutylaminocarbonylmethvnpyrrolidine-3-carboxylic acid Example 331 A Ethyl trans.trans-4-n .3-Benzodioxol-5-vn-2-fethvnyn-1 -f f N.N- dibutvlaminocarbonylmethvnpyrrolidine-3-carboxylat6 The title compound is made by employing the procedure of Corey and Fuchs (Tetrahedron Lett. 1972, 3769-72), using the compound of Example 327A. Example 331 B trans.trans-4-n .3-Benzodioxol-5-vn-2-fethvnvn-1 -ffN.N- dibutylaminocarbonylmethvnpyrrolidine-3-carboxylic acid The title compound is produced by reacting the compound of Example 331 A with lithium hydroxide according to the procedure of Example 71 C. Example 332 trans.trans--4-(1 ,3-Benzodioxol-5-yn-2-f 1 -pentvnvn-1-ffN.N- dibutylaminocarbonvlmethynpvrrolidine-3-carboxvlic acid Example 332A Ethyl trans.trans-4-( \ .3-Benzodioxol-5-yn-2-fpentvπvn-1 -f f N.N- dibutylaminocarbonylmethvnpyrrolidine-3-carboxylate The title compound is made by palladium-catalyzed coupling of the compound of Example 206A and propyl iodide, employing the procedure of Taylor, et. al. (J. Org. Chem. 1989, 54(15), 3618-24). Example 332B frans.frans-4-f1.3-Benzodioxol-5-vn-2-f1-pentynyn-1-ffN.N- dibutylaminocarbonylmethynpvrrolidine-3-carboxvlic acid The title compound is produced by reacting the compound of Example 332A with lithium hydroxide according to the procedure of Example 71 C. Example 333 frans-frans-2-f4-Methoxphenyh-4-f 1 .3-benzodioxol-5-yn- 1 -[2-(2.6- dioxopiperidinvh ethyl}-pvrrolidine-3-carboxylic acid The compound of example 61 A is added to a solution of the sodium salt of glutarimide in dimethylformamide. After stirring 24 hours, water is added and the mixture is extracted with ether. The resultant glutarimide is hydrolyzed to the title compound by the method of example 1D. Example 334 frans-frans-2-f4-Methoxyphenyh-4-f 1 .3-benzodioxol-5-yh-1 -fN.N- diphenylaminocarbonylmethyn-Pvrrolidine-3-carboxylic acid. The title compound was prepared according to the procedures described in Example 1. " >H NMR (300 MHz, CD 3 OD) δ 2.83 (dd, 1, J = 8.1 , 9.7), 2.98 (d, 1 , J = 15.4), 3.19 (t, 1 , J = 9.5), 3.4g (d, 1 , J = 15.3), 3.51 (dd, 1 , J = 4.6, g.5), 3.57 (m, 1), 3.7g (s, 3), 3.85 (d, 1 , J = 9.5), 5.90 (s, 2). 6.71 (d, 1 , J = 8.0), 6.84 (m, 3), 7.04 (d, 1 , J = 1.6), 7.14-7.16 (m, 6), 7.19-7.34 (m, 6); MS (DCI/NH3) m/z 551 ; Anal Calcd for C33H3θN2θ6-0.65H2θ.0.35C 2 H5θCOCH 3 : C, 69.77, H, 5.77, N, 4.76. Found: C, 69.75, H, 5.55, N, 4.64. Example 335 frans-frans-2-f4-Methoxyphenyh-4-f 1 .3-benzodioxol-5-yh-1 -[N.N- diisopropylaminocarbonylmethyn-pyrrolidine-3-carboxylic acid. The title compound was prepared according to the procedures described in Example 1. 1 H NMR (300 MHz, CD3OD) δ 0.95 (d, 3, J = 6.5), 1.24 (d, 3, J = 6.4), 1.30 (d, 6, J = 6.8), 2.85 (d, 1 , J = 12.5), 3.04 (dd, 1 , J = 8.1, 9.8), 3.14 (t, 1 , J = 9.7), 3.32-3.55 (m, 3), 3.63 (m, 1), 5.92 (s, 2), 6.75 (d, 1 , J = 8.1), 6.85 (dd, 1 , J = 1.7, 8.1), 6.93 (m, 2), 7.02 (d, 1 , J = 1.7), 7.35 (m, 2). MS (DCI/NH3) m/z 483. Anal Calcd for C27H34N2O6 -0.65 EtOAc: C, 65.86, H, 7.32, N, 5.19. Found: C, 5.74, H, 7.26, N, 5.52. Example 336 frans.frans-2-f 3-Fluoro-4-methoxyphenvh-4-f 1 .3-benzodioxol-5-vh- 1 -f2-N-propyl-N-butanesulfonylamino thyh-pyrrolidine-3-carboxylic acid Using the procedures described in Example 313 and Example 66, the title compound was prepared as a white solid. m.p.65-66°C. 1 H NMR (CDCI3, 300MHz) δ 0.82(t, J=7.5Hz, 3H), 0.92(t, J=7.5Hz, 3H), 1.34- 1.52(m, 4H), 1.72(quintet, J=7.5Hz,2H), 2.25-2.35(m,1 H), 2.72-2.94(m, 5H), 2.97-3.12(m, 2H), 3.19-3.46(m, 2H), 3.44(d, J=9Hz,1H), 3.53- 3.60(m, 1 H), 3.67(d, J=9Hz, 1 H), 3.89(s, 3H), 5.95(s, 2H), 6.74(d, J=8Hz, 1H), 6.82(d, J=8Hz, 1H), 6.92(t, J=9Hz, 1H), 6.97(s, 1 H), 7.12(d, J=9Hz, 1H), 7.18(d, J=12Hz, 1H). MS (DCI/NH3) m/e 565 (M+H) + . Example 337 Using methods described in the above examples, the compounds disclosed in Table 1 can be prepared. Table 1 R ° k "o * ^I 2. 3 ■ . h Table 1 cont. 7. 8. 9. 10. 11 - 12. 14. 15. 13. 16. 17. 18. 19. 20. 21. Table 1 cont. R 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. Table 1 cont. R R R 61. 62. 63. 64. 65. 66. 67. 68. 69. <Q Y^ Qyγ→ ( vγ^ 70. 71. 72. 73. 74. 75. 76. 77. 78. Table 1 cont. 79. 80. 81. 82. 83 - 84. 85. 86 - 87 - 88. 89. 90. 91. 92 " 93' 94. 95. 96. Table 1 cont. 97. 99. 98. 100. 101. 109. 110. 111. 112. 113. 114. 115. 1 16. 117. Table 1 cont. 130. 131. 132. 133. 134. 135. Table 1 cont. 139. 140. 141. 142. 143. 144. 145. 146. 147. 148. 149. 150. 151 - 152. 153. Table 1 cont. 154. 155. 156. 162. 160. 161. 163. 164. 165 166. 167. 168. Table 1 cont. 169. 170. 171 175. 176. 177. 178. 179. 180. 181. 182. 183. 187. 188. 189. Table 1 cont. R 192. 190. 191. 199. 200. 201. 205. 206. 207. Table 1 cont. R R R 211. 212. 213. 214. 215. 216. 217. 218. 219. 220. 221. 222. 226. 227. 1. . 230. 23 235. 236. 237. 244. 245. 246. 250. 251. 252. Table 1 cont. 254. 253. 255. 262. 263. 264. 66. . . 2 Table 1 cont. 271. 272. 273. 277. 278. 279. Table 1 cont. 283. 284. 285. Table 1 cont. 298. 299. 300. 301. 302. 303. 304. 305. 306. 307. 308. 309. 310. 311. 312. Table 1 cont. R R R 313. 314. 31 5- 316. 317. 318. 320. 321. 325. 326. 327. Table 1 cont. R 328. 329. 330. 331. 332. 333. . . 341. 342. 346. 347. 348. 349. 350. 351. 352. 353. 354. 355. 356. 357. Table 1 cont. R 361. 362. 363. 370. 371. 372. Table 1 cont. R R R 376. 377. 378. 382. 383. 384. 385. 386. 387. Table 1 cont. 391. 392. 393. Table 1 cont. Table 1 cont. 421. 422. 423. 432. 430 Table 1 cont. 451. 452. 453. 460. 461. 462. Table 1 cont. 467. 468. 469. 470. Table 1 cont. 502. 503. 504. 507. Table 1 cont. R R R . . 510. 511. 5 51122.. 513. 514. 515. 516. 517. 518. 520. 521. 522. Table 1 cont. 526 - 527. 528 . 529. 530. 531. 532. 533. 534. 535. 536. 537. Table 1 cont. 559. 560. 561. 565. 566. 567. Table 1 cont. 568. 569. 570. 571. 572. 573. 574. 575. 576. 592. 593. 594. 598. 599. 600. 601. 602. 603. Table 1 cont. R 604. 605. 606. 610. 611. 612. 614. 613. 615. Table 1 cont. 4. 622. 623. 62 634. 635. G 36 - 637. 638 - 639. 640. 646. 655. 656. 657. 658. 659. 660. 661. 662. 663. 664. 665 - 666. 667. 668. 669. 682. 683. 684. 705. . 708. 709. 710. 711. 712. 713. 714. 715. Example 338 Using methods described in the above examples, compounds comprising a parent structure selected from those disclosed in Table 2A and an R substituent selected from those disclosed in Table 2B can be prepared. Table 2A Table 2A cont, Table 2 A cont. Table 2A cont. 43. Table 2A cont. Table 2A cont. Table 2A cont. Table 2A cont. Table 2A cont. 118. 119. 120. Table 2 A cont. Table 2A cont. 154. 155. Table 2 A cont. Table 2A cont. 179. Table 2A cont. Table 2A cont. 193. 195. 194. Table 2A cont. Table 2 A cont. 223. 224. 225. 226. 227. Table 2 A cont. 232. 239. 240. Table 2A cont. 241. 242. 243. Table 2A cont. Table 2 A cont. 8. 269. 270. 277. 278. 279. Table 2 A cont. 283. 284. 285. 292. 293. 294. Table 2A cont. 8. 299. 300. Table 2A cont. 313. 314. 315. 319. 320. Table 2 A cont. Table 2 A cont. 337. 339. 338. 350. 351. Table 2A cont. 358. 359. 360. 362. 363. Table 2A cont. 367. 368. 369. 373. 374. 375. Table 2 A cont. 376. 377. 378. 382. 383. 384. 385. 386. 387. Table 2A cont. 390. 388. 389. 397. 398. 403. 404. 405. 412. Table 2A cont. 421. 422. 423. Table 2A cont. Table 2A cont. 450. 448. 449. 454. 455. 456. Table 2A cont. 458. 457. 459. 465. 463. 464. Table 2B 8. 10. 13. 4 - 1 5. 18. 16. 17. 19. 20. 21. Table 2B cont. R 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. 41. 42. Table 2B cont. R R R 43. 44. 45. 46. 47. 48. 52. 53. 54. 58. 60. Table 2B cont. R 65. 66. 73. 74. 75. 76. 77. 78. Table 2B cont. 79 80. 81. 82. 83. 84. 85. 86. 87. 91. 92. 93. 94. 95. 96. 97. 98. 99. Table 2B cont. R R R 103. 104. 105. 106. 107. 108. 109. 110. 111. 115. 116. 117. Table 2B cont. 121. 122. 123. 124. 125. 126. 127. 128. 129. 130. 131. 132. 144. 142. 143. 145. 146. 147. Table 2B cont. 192. Table 2B cont. R 205. 206. 207. 226. 227. 228. 229. 230. 231. 232. 233. 234. Table 2B cont. 241. 242. 243. 244. 245. 246. 249. 247. 248. 250. 252. Table 2B cont. 271. 272. 273. 277. 278. 279. 282. Table 2B cont. 286. 287. 288. 295. 296. 297. . 301. 302. 303. 307. 308. 309. 310. 311. 312. Table 2B cont. 313. 314. 315. Table 2B cont. 336. 334. 335 - 337. 338. 339 - 340. 341 342. 347. 348. 346. 367. 368. 369. 370. 371 - 372 - Table 2B cont. 376. 377. 378. 379. 380. 381. 382. 383. 384. 388. 389. 39α 418. 419. 420. 424. 425. 426. Table 2B cont. R R R 427. 428. 429. 430. 431. 433. 434. 435. 436 - 437' 438. 442' "43. 444. 445. 446. 447. . 449. 450. 457. 458. 459. Table 2B cont. 463. 464. 465. 472. 473 - 474. 475. 476. 477. 481. 482. 483. 484. 485. 486. XrV c irY χV 487. 488. 489. Table 2B cont. 490. 491. 492. 511. 512. 513. 514. 515, 516. 517. 518. 519. 520. 521. 522. Table 2B cont. 530. 531. 529. 535. 536. Sό 537V. Table 2B cont. R R 538. 539. 540. 547. 548. 549. 550. 551. 552. Table 2B cont. 556. 557. 558. 565. 566. 567. 580. 581. 582. 593. 594. 592. 596. 597. . 598. 599. 600. 601 • 602. 603. 611. :o V 612. Table 2B cont. R R 6 622. 623. 625. 626. 627. Table 2B cont. R R R 628. 629. 630. 631. 632. ι o Example 339 Using methods described in the above examples, compounds comprising a parent structure selected from those disclosed in Table 3A and an R substituent selected from those disclosed in Table 3B can be prepared. 1 5 Table 3A Table 3A cont. 21. 19. 20. Table 3B 8. 9. 18. 16. 17. 19. 20. 21. Table 3B cont. R 22. 23. 24. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. 41. 42. Table 3B cont. R R R 43. 44. 45. 46. 47. 48. 52. 53. 54. 55. 56. 57. 58. $ 59. 60. Table 3B cont. R R R ay ?v HsJ αv 61 ° CH3 63. 62. 65. 66. 67. 68. 69. 73. 74. 75. 76. 77. 78. Table 3B cont. 79. 80. 81. 82. 83. 84 85. 86. 87. 91 . 92. 93. 94. 95. 96. 97. 98. 99. Table 3B cont. R R R 103. 104. 105. 106. 107. 108. 109. 110. 111. 115. 116. 117. Table 3B cont. 127. 128. 129 - 130. 131. 132. Table 3B cont. 133. 134. 135. 136. 137. 138. 139. 140. 141. 144. 142. 143. 145. 146. 147. Table 3B cont. R R R 148. 149. 150. 151. 152. 153. 154 - 155. 156. 160. 161. . Table 3B cont. 166. 167. 168. 169. . 171. 175. 176. 177. Table 3B cont. 178. 179. 180. 181. 182. 183. 184. 185. 186. 192. Table 3B cont. 193. 194. 195. 205. 206. 207. 208. 209. 210. 220. 221. 222. Table 3B cont. 223. 224. 225. 226. 227. 228. 229. 230. 23 1 • 232. 233. 234. 236. 237. Table 3B cont. R R R 241. 242. 243. 244. 245. 246. 247. 248 249. 250. 252. Table 3B cont. R R R 266. 267. Table 3B cont. 271. 272. 273. 277. 278. 279. Table 3B cont. 286. 287. 288. 295. 296. 297. 298. 299. 300. 307. 308. 309. 310. 311. 312. Table 3B cont. R R R 313. 314. 315. Table 3B cont. R R R 335. 336. 334. 340. 341 342. 367. 368. 369. 370. 371 - 372. Table 3B cont. Table 3B cont. 427. 428. 429. 430. 431. 432. 433. 434. 435. 36' 437' 438. 442 - 443. 444. Table 3B cont. 445. 446. 447. 448. 449. 450. 457. 458. 459. Table 3B cont. 460. 461. 462. 463. 464. 465. 472. 473. 474. 487. 488. 489. Table 3B cont. R R R 490. 491. 492. 505. 506. 521. 522. Table 3B cont. n R R 524. 525. 523. 526. 527. 528. 530. 531. 529. Table 3B cont. R R 538. 539. 547. 548. 549. 550. 551. 552. Table 3B cont. R R R 556 557. 558. 567. Table 3B cont. 571. 572. 573. 577. 578. 580. 581. 582. Table 3B cont. 598. 599. 600. 601. 602. 603. Table 3B cont. 622. 623. 624. 625. 626. 627. Table 3B cont. 628. 629. 630. 631. 632. Example 340 trans. frans-4-M .3-Benzodioxol-5-vn-2- 4-methoxyphenyn-1 -f;N- (3-methylbut-1 -vh-N-phenyhaminocarbonylmethvh-pyrrolidlne-3- carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CD3OD) δ 0.85 (d, J=6 Hz, 6H), 1.25 (q, J=7 Hz, 2H), 1.42-1.56 (m, 1 H), 3.43-3.85 (m, 9H), 3.88s (3), 5.95 (s, 2H), 6.80 (d, J=7 Hz, 1 H), 6.86 (dd, J=9 Hz, 1 H), 6.89-7.00 (m, 2H), 6.97 (d, J=1 Hz, 1 H), 7.04 (d, J=9 Hz, 2H), 7.37 (d, J=9 Hz, 2H), 7.40- 7.47 (m, 3H). MS (C.I.) m7e C (53.12, 53.11), H (4.63, 4.80), N (3.33, 3.28). Example 341 trans. trans-4-( \ .3-Benzodioxol-5-vn-2-r / 4-methoxvphenvn-1 -I N- butyl-N-U-methylphenynaminocarbonylmethyh-pyrrolidine-3- carboxylic aςjd Using the procedures described in Example 1 , the title compound was prepared. H NMR (300 MHz, CD3OD) δ 0.87 (t, J=7 Hz, 3H), 1.20- 1.47 (m, 4H), 2.37 (s, 3H), 2.83 (q, J=7 Hz, 2H), 3.06-3.25 (m, 2H), 3.40- 3.50 (m, 1H), 3.51-3.63 (m, 3H), 3.80 (s, 3H), 3.87 (d, J=9 Hz, 1H), 5.92 (s, 2H), 6.74 (d, J=8 Hz, 1H), 6.80-6.86 (m, 3H), 6.89 (d, J=8 Hz, 2H), 7.04 (d, J=2 Hz, 1H), 7.12 (d, J=8 Hz, 2H), 7.19 (d, J=8 Hz, 2H). MS (DCI) m/e 545 (M+H)+. Analysis calcd for C32H36N2O6: C, 70.57; H, 6.66; N, 5.14. Found: C, 70.20; H, 6.81 ; N, 5.03. Example 342 frans.frans-4-M .3-Benzodioxol-5-vl^2- 4-DroDoxvphenvl -.f(7N.N- dibutylamino^carbonynmethvhpvrrolidine-3-carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H (300MHz, CDCI3 ) δ 7.30 (2H, d, J=9), 7.03 (1H, d, J=2), 6.83 (3H, m), 6.72 (1 H, d, J=9), 5.95 (1H, d, J=2), 5.93 (1H, d, J=2), 3.88 (2H, t, J=7), 3.73 (1H, d, J=12), 3.58 (1H, m), 3.53-3.20 (4H, m), 3.10-2.90 (4H, m), 2.72 (1H, d, J=15), 1.79 (2H, q, J=8), 1.50-1.05 (8H, m), 1.02 (3H, t, J=7), 0.87 (3H, t, J=7), 0.80 (3H, t, J=7). MS (DCI/NH3) m/e 539 (M+H)+. Anal calcd for C31 H42N2O6 • 0.5H2O: C, 67.98; H ,7.91 ; N, 5.11. Found: C.68.24; H, 7.70; N, 5.03. Example 343 frans.frans-4-M .3-Benzodioxol-5-vh-2-r4-DroDvlDhenvh-1 -fif.fN.N- dibutylamino^carbonvnmethvhDvrrolidine-3-carboxvlic acid Using the procedures described in Example 1 , the title compound was prepared. ^ H (300MHz, CDCI3 ) δ 7.31 (2H, d, J=9), 7.13 (2H, d, J=9), 7.03 (1H, d, J=2), 6.84 (1H, dd, J=6, 2), 6.73 (1 H, d, J=9), 5.95 (1H, d, J=2), 5.93 (1H, d, J=2), 3.76 (1H, d, J=10), 3.60 (1H, m), 3.55-3.20 (4H, m), 3.13-2.88 (4H, m), 2.75 (1 H, d, J=15), 2.55 (2H, t, J=8),1.62 (2H, q, J=8), 1.50-1.00 (8H, m), 0.92 (3H, t, J=7), 0.85 (3H, t, J=7), 0.78 (3H, t, J=7). MS (DCI/NH3) m/e 523 (MH+). Anal calcd for C31 H42N2O5 O.25 H2θ : C, 70.63; H, 8.13; N, 5.31. Found: C, 70.55; H, 8.08; N, 5.18. Example 344 frafis-frans-2-r4-Methoxvphenvn-4-f 1 .3-benzodioxol-5-yn- 1 -r3-fN- proDyl-N-n-pentanesulfonylamino ) propyl1pyrrolidine-3-carboxylic acid Using the procedures described in Example 316, the title compound was prepared. 1 H NMR (300MHz, CDCI3) δ 0.85 (t, J=7Hz, 3H), 0.90 (t, J=7Hz, 3H), 1.3-1.4 ( , 4H), 1.5-1.6 (sextet, J=7, 2H), 1.65-1.8 (m, 4H), 2.05-2.15 (m, 1H), 2.43-2.56 (m, 1 H), 2.72-3.1 (m, 7H), 3.27- 3.4 (m, 2H), 3.5-3.6 (m, 2H), 3.80 (s, 3H), 5.95 (s, 2H), 6.73 (d, J=8Hz, 1H), 6.8-6.9 (m, 1 H), 6. 85 (d, J= 9Hz, 2H), 7.02 (d, J=2Hz, 1H), 7.80 (d, J=9Hz, 2H). Example 5 frans.frans-4-n .2-Dihvdrobenzofuran-5-yh-2-(4-ethylphenvn-1 - f.ffN.N-dibutvlamino^carbonynmethynpvrrolidine-3-carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H (300MHz, CDCI3 ) δ 7.40 (3H, m), 7.22 (2H, d, J=8), 7.13 (1H, dd, J=8, 3), 6.72 (1 H, d, J=9), 5.28 (1 H, d, J=12), 4.55 (2H, t, J=9), 4.15 (1 H, d, J=18), 4.03 (2H, m), 3.75 (2H, m), 3.40 (2H, m), 3.20 (2H, t, J=9), 3.15 (1 H, m), 3.10-2.90 (2H, m), 2.63 (2H, q, J=9), 1.47 (2H, m), 1.31 (4H, m), 1.12 (3H, t, J=8), 1.10 (2H,m), 0.92 (3H, t, J=9), 0.80 (3H, t, J=9). MS (DCI/NH3) m/e 507 (M+H+). Anal calcd for C31 H42N2O4 • 1.0 TFA: C ,63.86 ; H, 6.98; N, 4.51. Found: C, 63.95; H, 7.12; N, 4.43. Example 346 frans.frans-4-M .3-Benzodioxol-5-yn-2-ι / 4-methoxyphenyn- 1 -(.ff N-f3- pentyn-N-phenylamino)carbonvhmethynpyrrolidine-3-carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CD3OD) δ 0.93 (t, J=7.3 Hz, 3H), 0.94 (t, J=7.3 Hz, 3H), 1.33 (m, 4H), 2.72 (d, J=15.2 Hz, 1 H), 2.81 (m, 1 H), 3.11-3.23 (m, 2H), 3.45-3.57 (m, 2H), 3.79 (s, 3H), 3.83 (d, J=9.8 Hz, 1 H), 4.54 (m, 1 H), 5.92 (s, 2H), 6.73 (d, J=7.8 Hz, 1 H), 6.83 (m, 3H), 6.98 (bs, 2H), 7.04 (d, J=1.7 Hz, 1 H), 7.07 (2), 7.37 (m, 3H). MS (DCI) m/e 545 (M+H+). Anal calcd for C32H33N2O6 • 0.35H2O: C, 69.76; H, 6.71 ; N, 5.08. Found: C, 69.72; H, 6.66; N, 4.94. Example 347 frans.frat7S-4-π .3-Benzodioxol-5-yn-2-f4-methoxyphenyn- 1 -(r(N- butyπ-N-f3-trifluoromethvlphenyhamino^carbonvπmethvnpyrrolidine- 3-carboxvlic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CD3OD) δ 0.87 (t, J=6.6 Hz, 3H), 1.17- 1.45 (m, 4H), 2.65 (d, J=16.5 Hz, 1H), 2.72 ( , 1 H), 3.10 (t, J=9.5 Hz, 1H), 3.21-3.27 (m, 1H), 3.40 (dd, J=4.1 , 9.9 Hz, 1H), 3.54 (m, 1H), 3.61- 3.74 (m, 3H), 3.77 (s, 3H). 5.93 (s, 2H), 6.73-6.85 (m, 4H), 7.02 (m, 3H), 7.33 (d. J=7.5 Hz, 1H). 7.40 (s, 1H), 7.58 (t, J=7.8 Hz, 1H), 7.69 (d, J=7.5 Hz, 1H). MS (DCI) m/e 599 (M+H+). Anal calcd for C32H33F3N2O6: C, 64.21 ; H, 5.56; N, 4.68. Found: C, 64.09; H, 5.63; N, 4.57. Example 348 trans. frans-4-M .3-Benzodioxol-5-vn-2-f4-methoxvphenyn-1 -fN- propyl-N-r4-morpholinylcarbony aminocarbonvlmethyn-pyrrolidine-3- carboxvlic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CD3OD) δ 0.78 (t, J=7 Hz, 3H), 1.43 (q, J=7 Hz, 2H), 2.07-3.01 (m, 1 H), 2.76 (dd, J=7, 9 Hz. 2H), 2.77-3.00 (m, 5H), 3.05 (3.70, J=m Hz, 11 H), 3.76 (s, 3H), 5.88 (s, 2H). 6.67 (d, J=8 Hz, 1H), 6.80 (dd, J=7 Hz, 1H), 6.83-6.90 (m, 2H), 6.98 (d, J=2 Hz, 1H), 7.32- 7.39 (m, 2H). MS m/e calc'd for (M+H) C29H39N3O7: (M+H) 540.2710,. Found (M+H) 540.2713. Example 349 trans. fraπs-4-M .3-Benzodioxol-5-vn-2-r4-methoxvDhenyn-1 -(c/s- 2.6-dimethylpiperidin-1 -vncarbonylmethyn-pyrrolidine-3-carboxvlic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CD3OD) δ 0.94 (d, J=7 Hz, 3H), 1.15d (7, 3H), 1.10-1.70 (m, 6H), 1.70-1.90 (m, 1H), 2.9. (d, J=13 Hz, 1 H), 3.00-3.20 (m, 2H), 3.50 (3.70, J=m Hz, 2H), 3.79 (s, 3H), 3.80-4.00 (m, 1 H), 4.10-4.65 (m, 2H), 5.95 (s, 2H), 6.70 (7.10, J=m Hz, 5H), 7.35 (m, 2H). MS m/e calc'd for (M+H)+ C28H35 2O6. (M+H) 495.2495. Found (M+H) 495.2493. Example 350 trans. frans-2-.f4-Methoxvmethoxvphenvn-4-.f i ,3-benzodioxol-5-yl)- 1 -f2-(N-propyl-N-n-pentanesulfonvlamino thvnDyrrolidine-3- cafboxyliς acid Using the procedures described in Example 1 , the title compound was prepared and isolated as a white solid, m.p. 57-59 °C. 1 H NMR (CDCI3, 300 MHz) δ 0.78 (t, J=7Hz, 3H), 0.90 (t, J=7Hz, 3H), 1.28-1.36 (m, 4H), 1.93 (sextet, J=7Hz, 2H), 1.72 (t, J=7Hz, 2H), 2.20-2.32 (m, 1 H), 2.72-3.10 (m, 7H), 3.18-3.41 (m, 2H), 3.43 (dd, J=3Hz, J=9Hz, 1 H), 3.48 (s, 3H), 3.52-3.59 (m. 1 H), 3.68 (d, J=9Hz, 1 H), 5.15 (s, 2H). 5.94 (s,2H), 6.73 (d, J=8Hz, 1 H), 6.82 (dd, J=1 Hz, J=8Hz, 1 H), 6.98-7.02 (m, 3H), 7.32 (d, J=9Hz, 2H). MS (DCI/NH3) m/e 591 (M+H)+. Example 351 frans.frans-4-M .3-Benzodioxol-5-yn-2-(4-methoxvphenvn-1-ffι / N-r2- butyπ-N-Dhenylamino^carbonynmethvnpyrrolidine-3-carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CD3OD) δ 0.79-0.89 (m, 6H), 1.14-1.21 (m, 1 H), 1.25-1.40 (m, 1 H), 2.64 (dd, J=4.6, 15.4 Hz, 1 H), 2.76 (t, J=9.0 Hz. 1H), 3.05-3.13 (m, 2H), 3.37-3.49 (m, 2H), 3.70 (s, 3H), 3.80 (d, J=9.8 Hz, 1 H), 4.53 (m, 1 H), 5.83 (m, 2H), 6.65 (d, J=8.1 Hz, 1 H), 6.72 (- 6.76, J=m Hz, 3H), 6.87 (m, 2H), 6.95 (d, J=1.7 Hz, 1 H), 7.03 (m, 2H), 7.29 (m, 3H). MS (DCI) m/e 531 (M+H+). Anal calcd for C31 H34N2O6 ■ 0.4H2O: C, 69.23; H, 6.52; N, 5.21. Found: C, 69.19; H, 6.52; N, 5.03. Example 352 frans. frans-4-M .3-Benzodioxol-5-yn-2-(4-methoxyphenyn- 1 -(.f-f N-ιf 2- propyn-N-phenvlamino)carbonvnmethvnpvrrolidine-3-carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CD3OD) δ 0.99 (d, J=6.8 Hz, 6H), 2.71 (d, J=15.6 Hz, 1 H), 2.84 (m, 1 H), 3.13-3.18 (m, 2H), 3.45-3.58 (m, 2H), 3.79 (s, 3H), 3.88 (d, J=9.8 Hz, 1 H), 4.80 (m, 1 H), 5.92 (s, 2H), 6.74 (d, J=8.1 Hz, 1H), 6.83 (m, 3H), 6.96 (br s, 2H). 7.04 (d. J=1.7 Hz, 1 H), 7.13 (m, 2H), 7.38 (m, 3H). MS (DCI) m/e 517 (M+H+). Anal calcd for C30H32N2O6 • 0.4H2O • O.O8CH3CO2C2H5: C, 68.65; H, 6.28; N, 5.28. Found: C, 68.64; H, 6.35; N, 5.14. Example 353 frans.frans-4-(4-ProDoxvphenvn-2-(4-methoxvDhenvn-1 -tttN N- dibutylamino arbonynmethvnpvrrolidine-3-carboxyliπ aniri Using the procedures described in Example 1 , the title compound was prepared. 1 H (300MHz, CDCI3 ) δ 7.42 (2H, d, J=10Hz), 7.38 (2H, d, J=10Hz), 6.92 (2H, d, J=10Hz), 6.88 (2H, d, J=10Hz), 5.13 (1 H, bd, J=12Hz), 4.02 (2H, m), 3.90 (2H, t, J=8Hz), 3.80 (3H, s), 3.71 (3H, m), 3.40 (2H, m), 3.19 (1 H, m), 3.10-2.90 (2H, m), 1.80 (2H, m), 1.48 (2H, m), 1.29 (4H, m), 1.13 (2H, m), 1.03 (3H, t. J=8Hz), 0.92 (3H, t, J=9Hz), 0.82 (3H, t, J=9Hz). MS (DCI/NH3) m/e 525 (MH+). Anal calcd for C31 H44N205- 1 TFA : C, 62.06 H 7.10; N, 4.39 . Found: C, 62.43; H, 7.28; N, 4.39. Example 354 frans. frans-4-M .3-Benzodioxol-5-vn-2-(4-methoxvphenyn- 1 - fπ .2.3.4-tetrahvdroquinolin-1 -vncarbonyπmethvnpyrrolidine-3- carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CD3OD) δ 1.88 (quintet, J=6.5 Hz, 2H), 2.67 (t, J=6.4 Hz, 2H), 2.87 (t, J=8.6 Hz, 1 H), 3.14 (m, 2H). 3.42 (dd. J=4.6, 9.7 Hz, 1 H), 3.53-3.70 (m, 3H), 3.72-3.78 (m, 1 H), 3.77 (s, 3H), 3.86 (d, J=9.6 Hz, 1 H), 5.91 (s, 2H), 6.73 (d, J=8.1 Hz, 1 H), 6.83 (m, 3H), 6.98 (d, J=1.1 Hz, 1 H), 7.02-7.23 (m, 6H). MS (DCI) m/e 515 (M+H+). Anal calcd for C30H30N2O6 • O.3H2O • 0.15 CH3CO2C2H5: C, 68.93; H, 6.01 ; N, 5.25. Found: C, 68.91 ; H, 5.86; N, 5.19. Example 355 trans.t rans-2-ι , 3.4-Dimethoxyphenyn-4-M .3-benzodioxol-5-yn-1 - (N.N-di.fn-butynamino carbonvnmethyn-pyrrolidine-3-carboxylic acid Using the procedures described in Example 1 , the title compound was prepared and isolated as a white solid, m.p. 64-65 °C. 1 H NMR (CDCI3, 300MHz) δ 0.79 (t, J=7Hz, 3H), 0.88 (t, J=7Hz, 3H),1.07 (sextet, J=7Hz, 2H), 1.20-1.35 (m. 4H), 1.43 (sextet, J=7Hz, 2H), 2.83 (d, J=13.5Hz, 1 H), 2.94-3.17 (m, 4H), 3.22-3.42 (m. 1 H), 3.40-3.48 (m, 3H), 3.58-3.65 (m, 1H), 3.82 (s, 3H), 3.85 (s, 4H),5.92 (s, 2H), 6.73 (d, J=8Hz, 1H), 6.81 (d, J=8Hz, 1H), 6.86-6.96 (m. 3H), 7.07 (d, J=3Hz, 1H). MS (DCI/NH3) m/e 541 (M+H)+. Example 356 frans.frans-2-f3.4-DimethoxvDhenvn-4-f 1 .3-benzodioxol -5-vh-1 -r2- (N-propyl-N-n-pentanesulfonvlamino^ethynpvrrolidine-3-carboxylic 3Cid Using the procedures described in Example 1 , the title compound was prepared and isolated as a white solid, m.p. 75-86 °C. 1 H NMR (CD3OD, 300 MHz) δ 0.75 (t, J=7Hz, 3H), 0.82 (t, J=7Hz, 3H), 1.32-1.43 (m, 6H), 1.65-1.77 (m, 2H), 3.0-3.09 (m, 4H), 3.23-3.27 (m, 2H), 3.44 (t. J=6Hz, 1H), 3.47-3.56 (m, 2H), 3.78 (d, J=9Hz, 1 H), 3.83-3.93 (m, 2H), 3.87 (s, 3H), 3.92 (s, 3H), 4.63 (d, J=13Hz. 1H), 5.97 (s, 2H), 6.82 (d, J=7Hz, 1H), 6.93 (d, J=7Hz, 1H), 7.06 (d, J=7Hz, 1 H), 7.08 (d, J=3Hz, 1H), 7.16 (dd, J=3Hz, J=7Hz, 1 H), 7.27 (d, J=3Hz. 1 H). MS (DCI/NH3) m/e 591 (M+H)+. Example 357 frans.frans-2-(3.4-Dimethoxyphenvn-4-M .3-benzodioxol-5-yn-1 -f2- (N-Dropyl-N-n-hexanesulfonylamino)ethyl1pyrrolidine-3-carboxylic acid Using the procedures described in Example 1 , the title compound was prepared and isolated as a white solid, m.p. 65-66 °C. " Η NMR (CDCI3, 300 MHz) δ 0.80 (t, J=7Hz, 3H), 0.89 (t, J=7Hz, 3H), 1.23-1.48 (m, 6H), 1.43 (sextet, J=7Hz, 2H), 1.72 (sextet,J=7Hz, 2H), 2.25-2.35 (m. 1H), 2.73-3.10 (m, 7H), 3.19-3.32 (m, 2H), 3.45 (dd, J=3Hz, J=9Hz, 1 H), 3.53-3.59 (m, 1 H), 3.68 (d, J=9Hz, 1 H),3.87 (s, 6H), 5.95 (s, 2H), 6.74 (d, J=8Hz, 1H), 6.79-6.86 (m, 2H), 6.92-6.97 (m, 2H), 7.02 (s, 1H). MS (DCI/NH3) m/e 605 (M+H)+. Exampie 358 frans. rans-2-f4-Methoxyphenvn-4-M .3-benzodioxol-5-vn-1 -f2- {phthalimidoϊethvn-pvrrolidine-3-carboxylic acid The compound of Example 1C (250 mg), N-bromoethylphthalimide (206 mg), and diisopropylethylamine (175 mg) were dissolved in 1 mL of acetonitrile and heated for 2.5 hours at 95 °C. Toluene was added, and the mixture was washed with KHCO3 solution. The solution was dried (Na2Sθ4) and concentrated. The crude product was purified by chromatography on silica gel eluting with 3:1 EtOAc-hexane to give 216 mg of an intermediate ethyl ester which was hydrolyzed by the method of Example 1 D to give 130 mg of the title compound as a white powder. H NMR (300 MHz, CDCI3) δ 3.12-3.26 (m, 2H), 3.60-3.75 (m, 2H), 3.70 (s, 3H), 3.98-4.12 (m, 2H), 4.45-4.55 (m, 1 H), 4.69 (d, J=9Hz, 1 H), 4.76- 4.88 (m, 1 H), 5.96 (s, 2H), 6.55 (d, J=8Hz, 1H), 6.60-6.70 (m, 3H), 6.79 (d, J=8Hz, 1 H), 7.05-7.45 (m, 5H), 7.75 (d, J=7Hz, 1H). Example 359 frans. frans-4-M .3-Benzodioxol-5-vh-2-r4-methoxvDhenvn- 1 -ffι / N-ιf2- pentyh-N-phenylamino^carbonvπmethyπpyrrolidine-3-carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CD3OD) δ 0.86-0.98 ( , 6H), 1.17-1.22 (m, 1H), 1.23-1.41 (m, 3H), 2.70 (dd, J=1 1.2, 15.3 Hz, 1 H), 2.83 (m, 1 H), 3.10-3.21 (m, 2H), 3.45-3.60 (m, 2H), 3.79 (s, 3H), 3.86 (m, 1 H), 4.74 (m, 1H), 5.91 (m, 2H), 6.73 (dd, J=1.1 , 7.7 Hz. 3H), 6.82 (m, 2H), 7.04- 7.14 (m, 3H), 7.36 (m, 3H). MS (DCI) m/e 545 (M+H+). Anal calcd for C32H36N2O6 ■ 0.25 CH3CO2C2H5: C, 69.95; H, 6.76; N, 4.94. Found: C, 70.03; H, 6.54; N, 4.78. Example 360 trans, frans-4-r 1 .3-Benzodioxol-5-yh-2- -methoxyphenvh-1 -if N- butyl-N-ιf2-naDhthvπaminocarbonylmethvn-pyrrolidine-3-carboxylic add Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CD3OD) δ 0.83 (t, J=7 Hz, 3H), 1.23- 1.39 (m, 4H), 1.40-1.55 (m, 3H), 2.60-2.72 (m, 2H), 3.00-3.80 (m, 5H), 3.66 (s, 3H), 5.87 (s, 2H), 6.39 (d, J=9 Hz, 2H), 6.74-6.85 (m, 3H), 7.17 (d, J=2 Hz, 1 H), 7.40 (dd, J=8 Hz, 1 H), 7.52-7.62 (m, 3H), 7.80-7.90 (m, 1H), 7.90-8.00 (m, 2H). MS (DCI) m/e 581 (M+H)+. Analysis calcd for C35H36N2O6 • 0.3 H2O: C, 71.73; H, 6.29; N, 4.78. Found: C, 71.74; H, 6.26; N, 4.72. Example 361 trans. trans-2-( 4-Propoxyphenvn-4-M .3-benzodioxol-5-yn-1 -r2-fN- propvl-N-n-pentanesulfonylamino)ethvnpvrrolidine-3-carboxylic acid Using the procedures described in Example 66, the title compound was prepared and isolated as a white solid, m.p. 53-54 °C. 1 H NMR (CDCI3, 300MHz) δ 0.79 (t, J=7Hz, 3H), 0.89 (t, J=7Hz, 3H), 1.03 (t, J=7Hz, 3H), 1.24-1.34 (m, 4H), 1.43 (sextet, J=7Hz, 2H), 1.67-1.75 (m, 2H), 1.80 (sextet, 2H), 2.23-2.33 (m, 1 H). 2.72-2.93 (m, 5H), 3.05 (septet, J=7Hz, 2H), 3.15-3.35 (m, 2H), 3.42 (d, J=9Hz, 1 H), 3.54-3.62 (m, 1H), 3.67 (d, J=9Hz, 1H), 4.90 (t, J=7Hz, 2H), 5.95 (s, 2H). 6.73 (d, J=8Hz, 1H), 6.85 (d, J=8Hz, 2H), 7.02 (s, 1 H), 7.32 (d, J=8Hz. 2H). MS (DCI/NH3) m/e 589 (M+H)+. Example 362 frans. frans-4-n .3-Benzodioxol-5-yn-2-ιf 4-methoxyphenyn- 1 -r(2- methylindolin-1 -yncarbonyhmethyhpvrrolidine-3-carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CD3OD) δ mixture of indole C2 diastereomers, 0.95 (m, 1.5 (CH3 )), 1.05 (d, 6.3H, 1.5 (CH3)), 2.62 (m, 1 H), 3.01 (m, 2H), 3.14-3.25 (m, 1 H), 3.37-3.52 (m, 1.5H), 3.56-3.80 (m, 2H), 3.65 (S, 1.5 (CH3O)), 3.76 (s, 1.5 (CH3O)), 3.93 (m, 0.5H), 4.05-4.13 (m, 0.5H,). 4.42 (m, 0.5H), 4.65-4.74 (m, 1 H), 5.91 (m, 2H), 6.72 (d, J=8.1 Hz, 0.5H), 6.75 (m, 0.5H), 6.85 (m, 2H), 6.92 (d. J=8.5 Hz, 1 H), 7.00-7.06 (m, 2H), 7.14 (t, J=7.7 Hz, 1 H), 7.21 (t, J=6.6 Hz, 1 H), 7.38 (m, 2H), 7.99 (m, 1H). MS (DCI) m/e 515 (M+H+). Anal calcd for C30H30N2O6 • 0.35H2O • 0.3 CH3CO2C2H5: C, 68.47; H, 6.10; N, 5.12. Found: C, 68.46; H, 5.97; N, 5.07. Eyample 363 frans. frans-4-n .3-Benzodioxol-5-yn-2-r4-methoxyphenvn- 1 - - hydroxy-3-propvlhex-1 -vhpyrrolidine-3-carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CD3OD) δ 1.06 (m, 6H), 1.26-1.60 (m, 9H), 3.16 (dd, J=10.9, 12.6 Hz, 1 H), 3.18 (d, J=11 Hz, 1 H), 3.44 (d, J=2.0 Hz, 1 H), 3.61 (t, J=11 Hz, 1 H), 3.73 (t, J=11.0 Hz. 1 H), 3.85 (m, 1 H), 3.96-4.17 (m, 2H), 4.02 (s, 1.5 (CH3O diastereomer)), 4.03 (s, 1.5 (CH3O diastereomer)), 6.15 (s, 2H). 7.01 (d, J=8.1 Hz. 0.5H). 7.00 (d, J=8.1 Hz, 0.5H), 7.10 (m, 1 H), 7.23 (m, 3H), 7.77 (m, 2H). MS (DCI.) m/e 484 (M+H+). Anal calcd for C28H37NO6 ■ 0.33 H3PO4: C, 65.34; H, 7.44; N, 2.72. Found: C, 65.30; H, 7.40; N, 2.60. Example 364 frans. frans-4-M .3-Benzodioxol-5-yn-2-r4-methoxyphenvn- 1 - fN-f4- heρtyπ-N-(f3.4-dimethoxybenzyhamino^carbonvhmethyπDyrrolidine-3- carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CD3OD) δ1 :1 mixture of rotamers, 0.61 (t. J=7.1 Hz, 1.5H), 0.72 (7.3, 1.5H), 0.76 (t, J=7.1 , 1.5, 0.83, t, 7.3 Hz, 1.5H), 1.05-1.60 (m, 8H). 2.84-3.10 (m, J=2.5, 3.18, t, 9.7 Hz. 0.5H). 3.41-3.52 (m, 2H). 3.47-3.69 (m, 2H), 3.66 (s, 1.5H), 3.73 (s, 1.5H), 3.77 (s, 1.5H), 3.78 (s, 1.5H), 3.79 (s. 1.5H), 3.86 (d, J=9.8 Hz. 0.5H), 4.19 (d, J=17.7 Hz, 0.5H), 4.29 (d, J=15.2 Hz, 0.5H), 4.40-4.49 (m, 0.5H), 4.47 (d, J=15.3 Hz, 0.5H), 4.60 (d, J=17.6 Hz, 0.5H), 5.93 (m, 2H), 6.46 (dd, J=1.7, 8.2 Hz, 0.5H), 6.52 (d. J=2.0 Hz, 0.5H), 6.74 (m, 2.5H), 6.80 (s. 1 H). 6.83- 6.88 (m, 1 H), 6.92 (m, 1.5H), 7.03 (dd, J=1.7, 6.8 Hz. 1 H), 7.19 (m, 1H), 7.36 (m, 1H). MS (DCI) m/e 647 (M+H+). Anal calcd for C37H46N2O8: C, 68.71 ; H, 7.17; N, 4.33. Found: C, 68.41 ; H, 7.26; N, 4.11. Example 365 frans. frans-4-f 1 .3-Benzodioxol-5-yn-2-(4-methoxvDhenvn- 1 - . πndolin-1 -yl)carbonvπmethvhpyrrolidine-3-carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CD3OD) δ2.97 (dd, J=8.1 , 9.5 Hz, 1 H), 3.10 (t, J=8.1 Hz, 2H), 3.16-3.22 (m, 2H), 3.51-3.68 (m, 3H), 3.73 (m, 3H), 3.83-4.05 (m. 3H), 5.90 (m, 2H), 6.73 (d, J=8.1 Hz, 1 H), 6.86 (m, 3H), 6.99 (dt. J=1.1 , 7.4 Hz. 1 H). 7.08 (d, J=0.7 Hz, 1 H), 7.11 (m, 1H), 7.18 (d. J=7.1 Hz, 1 H), 7.38 (d, J=8.5 Hz, 2H), 8.02 (8.1 , 1 H). MS (CI.) m/e 501 (M+H+). Anal calcd for C29H28N2O6 • 0.5 H2O - 0.15 CH3CO2C2H5: C, 68.01; H, 5.82; N, 5.36. Found: C, 68.03; H, 5.65; N, 5.25. Example 366 trans, frans-4-π ■3-Benzodioxol-5-vh-2- ( 4-methoxyphenyh-1 -(N- butyl-N-ιf2-chlorθDhenyπaminocarbonylmethyhpyrrolidine-3- carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CD3OD) δθ.89 (dt, J=7 Hz, 3H), 1.23- 1.51 (m, 4H), 2.52-4.00 (m, 8H), 3.78 (d. J=6 Hz, 3H), 5.92 (d, J=6 Hz, 2H), 6.70-6.87 (m, 4H), 7.02-7.21 (m, 4H), 7.27-7.52 (m, 3H). MS (DCI) m/e 565 (M+H)+. Analysis calcd for C31 H32N2O6CI • O.6H2O: C, 64.66; H, 5.99; N, 4.86. Found: C, 64.59; H, 6.00; N, 4.64. Example 367 trans. trans-2-( 4-Methoxphenyl )-4-M .3-benzodioxol-5-vh-1 - (3.4.5-trimethoxybenzvnpyrrolidine-3-carboxylic acid The compound resulting from Example 1C (0.25 g) was reacted with 0.169 g of 3,4,5-trimethoxybenzyl chloride and 0.175 g of diisopropylethylamine in 1 mL of acetonitrile for 2 hours at room temperature. The resulting ester was isolated and then hydrolyzed by the method of Example 1D to give 0.193 g of the title compound, m.p. 108-110 °C. 1 H NMR (300 MHz, CDCI3) δ2.75 (t, J=9Hz, 1 H), 2.95-3.05 (m, 2H), 3.20 (d, J=11 Hz, 1H). 3.45-3.55 (m, 1 H), 3.7-3.8 (m, 2H), 3.84 (s, 3H), 5.95 (dd, J=2Hz, 6Hz, 2H), 6.55 (s, 2H), 6.70 (d, J=8Hz, 1 H), 6.30-6.35 (m, 1 H), 6.90 (d, J=9Hz, 2H), 7.13 (d, J=2Hz, 1H), 7.43 (d, J=9Hz, 2H). Example 368 frans. frans-4-f 1 .3-Benzodioxol-5-yn-2-(4-methoxvphenvh-1 -f N- butyl-N-ιf3-chlorophenvhaminocarbonylmethvn-pyrrolidine-3- carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CD3OD) δ θ.89 (t, J=7 Hz, 3H), 1.20- 1.42 (m, 4H), 3.42-3.87 (m, 9H), 3.9 (s, 3H), 5.96 (s, 2H), 6.75 (7.10, J=m Hz. 7H). 7.33-7.50 (m, 4H). MS (CI.) m/e 565(M+H). Analysis calcd for C3l H33N2θ6CM .0CF3COOH: C. 58.37; H, 5.05; N, 4.13. Found: C, 58.41; H, 4.99; N, 4.08. Example 369 frans. frans-2-(4-Methoxphenyπ-4-t; i .3-benzodioxol-5-yπ-1 -r2-fdi-n- butylamino)pyrimidin-4-vnpyrrolidine-3-carboxylic acid The compound resulting from Example 1C (0.25 g) was reacted with 0.11 g of 2,4-dichloropyrimidine and 0.175 g of diisopropylethylamine in 1 mL of acetonitrile for 2 hours at room temperature to give 0.218 g of ethyl 2-(4-methoxphenyl)-4-(1 ,3- benzodioxol-5-yl)- 1 -(2-chloro-4-pyrimidyl)-pyrrolidine-3- carboxylate. This compound was reacted with 1 mL of dibutylamine in 2 mL of toluene at 125 °C for 17 hours. The resulting ethyl ester was hydrolyzed by the method of Example 1 D to give 0.142 g of the title comopund as a white powder. 1 H NMR (300 MHz, CDCI3) δO.75-0.90 (broad, 6H). 1.1-1.3 (br. 4H). 1.35-1.55 (br, 4H), 3.05 (m, 1 H), 3.3-3.5 (br, 2H), 3.55-3.67 (m, 2H), 3.75 (s, 3H), 4.6 (br, 1 H), 5.2 (br, 1H), 5.45 (br, 1 H), 5.87 (s, 2H), 6.3 (br, 1 H), 6.67 (d, J=8Hz, 1 H), 6.7-6.85 (m. 4H), 7.10 (d, J=9Hz, 2H). Example 370 frans. frans-4-M .3-Benzodioxol-5-yn-2-f4-methoxvphenvn- 1 -f r.f N-r2- methylbut-2-yl )-N-phenylamino^carbonvhmethynpyrrolidine-3- carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CD3OD) δ 0.90 (t, J=7.5 Hz, 3H), 1.12 (S, 3H), 1.14 (s, 3H), 2.06 (q, J=7.5 Hz, 2H), 2.73 (d, J=15.3 Hz, 1 H), 2.91 (t. J=9.5 Hz, 1 H), 3.11 (d, J=15.6 Hz. 1 H), 3.21 (t, J=8.8 Hz, 1 H), 3.50- 3.61 (m. 2H), 3.80 (s. 3H). 4.00 (d, J=10.2 Hz, 1 H), 5.91 (s, 2H), 6.74 (d, J=7.8 Hz, 1 H), 6.85 (m, 3H), 6.93 (m, 1 H), 6.98 (m. 1 H), 7.03 (d, J=1.7 Hz, 1 H). 7.17 (m. 2H), 7.36 (m. 3H). MS (DCI) m/e 545 (M+H+). Anal calcd for C32H36N2O6. C. 70.57; H, 6.66; N, 5.14. Found: C, 70.17; H, 6.53; N, 4.97. Example 371 frans. rans-2- -EthvlPhenvn-4-ιf5-indanvn- 1 -f N .N- riihntvlamino arbonvlmethyhpyrrolidine-3-carboxvlic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H (300MHz, CDCI3) δ 7.25 (3H, m), 7.21 (1H, d, 3Hz), 7.17 (3H, m), 3.80 (1 H, d, 10Hz), 3.65 (1 H, ddd, 6, 5, 3Hz), 3.4 (4H, m), 3.10 (2H, m), 2.98 (2H, m), 2.88 (5H, m), 2.79 (1 H, d, 16Hz), 2.62 (2H, q, 7Hz), 2.05 (2H, m), 1.42 (2H, m), 1.32 (1 H, m), 1.21 (3H, t, 7Hz), 1.05 (2H, sext, 7Hz), 0.87 (3H, t, 7Hz). 0.79 (3H, t, 7Hz). MS (DCI, NH3) m/e 505 (M+H+). Anal calcd for C32H44N2O3: C, 76.15; H, 8.79; N 5.55. Found: C, 75.96; H, 8.75; N, 5.36. Example 372 trans. rans-2-.f3.4-Difluorophenyn-4-M .3-benzodioxol-5-yn-1 -( ' f'. N.N- dibutylamino^carbonvhmethyh-pyrrolidine-3-carboxylic acid Using the procedures described in Example 1 , the title compound was prepared and isolated as a white solid, m.p. 62-63 °C 1 H NMR (CDCI3, 300 MHz), δ 0.83 (t, J=7Hz, 3H), 0.88 (t, J=7Hz, 3H), 1.13 (sextet, J=7Hz, 2H), 1.20-1.32 (m,3H), 1.36-1.49 (m,3H), 2.85-2.93 (m,2H), 2.98-3.23 (m, 4H), 3.36-3.45 (m, 3H), 3.58-3.66 (m 1 H), 3.94 (d, J=8Hz, 1 H), 5.93 (s, 2H), 6.72 (d, J=7.5Hz, 1 H), 6.84 (dd, J=1Hz, J=7.5Hz, 1 H), 6.98 (d. J=7.5Hz, 1 H), 7.08-7.15 (m, 2H), 7.22-7.28 (m, 1 H). MS (CDI/NH3) m/e517 (M+H)+. Example 373 frans. frans-2-(3.4-Difluoro p henvh-4-n .3-benzodioxol-5-vπ- 1 -[2- / N- Dropyl-N-n-pentanesulfonylamino thyllpyrrolidine-3-carboxylic acid Using the procedures described in Example 1 , the title compound was prepared and isolated as a white solid, m.p. 71-72 °C 1 H NMR (CDCI3, 300 MHz) δ 0.82 (t, J=7Hz, 3H), 0.90 (t, J=7Hz, 3H), 1.25-1.38 (m, 4H), 1.46 (sextet, J=7Hz, 2H), 1.74 (quintett, J=7Hz, 2H), 2.26-2.36 (m, 1 H), 2.72-2.95 (m, 5H), 2.98-3.12 (m, 2H), 3.15-3.34 (m, 2H), 3.45 (dd, J=3Hz, J=9Hz, 1 H), 3.53-3.60 (m, 1 H), 3.71 (d, J=9Hz, 1 H), 5.96 (s, 2H), 6.75 (d, J=9Hz, 1 H), 3.82 (dd„ J=2Hz, J=9Hz, 1 H), 5.96 (d, J=2Hz, 1 H), 7.09-7.18 (m, 2H), 7.23-7.34 (m, 1 H). MS (CDI/NH3) m/e567 (M+H)+. Example 374 frans. frans-4-M .3-Benzodioxol-5-vl^2-.fethoxvmethyl -(7(:N . N- dibutylaminotearbonvnmethvhpvrrolidine-3-carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. TLC (10% MeOH-CH2Cl2) Rf = 0.53. 1 H NMR (CDCI3, 300 MHz, rotameric forms) δ 0.70 (t, J=7Hz), 0.80 (t, J=7Hz) and 0.96-1.04 (m, 6H total), 1.04-1.75 (m, 11 H), 1.34-1.53 (br m, 4H), 2.65 (AB) and 2.80-3.08 (m, 2H total), 3.10-3.82 (br m, 12H), 4.03 (m) and 4.22-4.45 (br m, 2H total), 5.90 (s) and 5.91 (s, 2H total), 6.65-6.84 (m) and 6.93 (m) and 6.99 (m, 3H total). MS (FAB) m/e 463 (M+H)+. Anal calcd for C25H38N206 - 1.5 H2O: C, 61.33; H, 8.44; N, 5.72. Found: C, 61.28; H, 7.78; N, 5.62. Example 375 frans. frans-4-M .3-Benzodioxol-5-vn-2-(n-butvn- 1 -^(N. N- dibutylamino arbonyπmethvπpyrrolidine-3-carboxylic acid Using the procedures described in Example 1 , the title compound was prepared and isolated as a colorless wax. TLC (10% MeOH-CH2Cl2) Rf = 0.37. 1 H NMR (CDCI3, 300 MHz, rotameric forms) δ 0.71 (t, J=7Hz) and 0.77-1.05 (m, 9H total), 1.05-1.20 (m, 2H), 1.20-1.72 (br , 13H), 2.48-2.52 (m, 1 H), 2.87-3.00 (m, 1 H), 3.05-3.60 (m, 5H), 3.60-3.80 (br m, 2H), 3.88-4.05 (br m, 1 H), 4.28 (br d, J=15Hz, 1 H total), 5.90 (s) and 5.92 (s, 2H total), 6.67-6.82 (m, 3H total). MS (FAB) m/e 461 (M+H)+. Anal calcd for C26H40N2O5 • 1 -75 H2O: C, 63.45; H, 8.90; N, 5.69. Found: C, 63.18; H, 8.22; N, 5.60. Example 376 frans. frans-4-f 1 .3-Benzodioxol-5-vn-2-f2-methylbutvh-1 -frfN.N- dibutylamino^carbonvhmethvhpvrrolidine-3-carboxvlic acid Using the procedures described in Example 1 , the title compound was prepared and isolated as a colorless glass. TLC (10% MeOH- CH2CI2) Rf = 0.49. 1 H NMR (CDCI3, 300 MHz, rotameric forms and mixture of diastereomers) δ 0.69 (br t, J=7Hz) and 0.75-2.15 (several br m, approx. 26H total), 2.48-2.65 (br m, 1 H), 2.87-3.01 (br m, 1 H), 3.06-3.82 (br m, 7H), 3.90-4.40 (br m, 2H), 5.90 (s) and 5.92 (s, 2H total), 6.67-6.90 (m, 3H total). MS (FAB) m/e 475 (M+H)+. Example 377. frans. frans-4-r i .3-Benzodioxol-5-yn-2-ι / 3-methylbutyπ-1 -^fN.N- dibutylamino^carbonvhmethyhpyrrolidine-3-carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. TLC (10% Me0H-CH2Cl2) Rf = 0.41. " Η NMR (CDCI3, 300 MHz, rotameric forms) δ 0.73 (t, J=7Hz) and 0.77-1.05 (m, 12H total). 1.07-1.75 (m, approx. 14H plus H2O). 2.48-2.63 (m, 1 H), 2.87-3.05 (m, 1 H), 3.05-3.60 (several br m, 5H), 3.62-4.02 (br m, 2H), 4.29 (br d. J=15Hz, 1H), 5.89 (s) and 5.93 (s, 2H total), 6.65-6.90 (m, 3H total). MS (FAB) m e 475 (M+H)+. Example 378 frans. frans-2-ι / 4-Methoxyphenvπ-4-( 1 .3-benzodioxol-5-vh-1 - 2-ιfN- propyl-N-( N-methyl-N-propylamino)sulfonvπamino thvMpyrrolidine- 3-carboxylic acid Using the procedures described in Example 66, the title compound was prepared and isolated as a white solid, m.p. 58-59 °C. 1 H NMR (CDCI3, 300MHz) o 0.78 (t, J=7Hz, 3H), 0.90 (t, J=7Hz, 3H), 1.27 (sextet, J=7Hz, 2H), 1.48 (m. 4H), 2.22-2.30 (m, 1 H), 2.62 (s, 3H), 2.68-2.78 (m, 1 H), 2.84-3.03 (m, 5H), 3.08-3.31 (m, 3H),3.39 (dd, J=3Hz, J=9Hz,1 H), 3.50-3.58 (m, 1H), 3.63 (d, J=9Hz, 1H),3.79 (s, 3H), 5.95 (s, 2H), 3.73 (d, J=8Hz, 1H), 6.83 (dd, J=2Hz, J=8Hz, 1 H), 3.87 (d. J=9Hz, 2H), 7.01 (d, J=2Hz, 1 H), 7.33 (d, J=9Hz, 2H). MS (DCI/NH3) m/e 576 (M+H)+. Example 379 frans.frans-2.4-Dir3.4-difluorophenyn- 1 -(((N . N- dibutylamino^carbonvnmethvn p vrrolidine-3-carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300MHz, CDCI3 ) δ 7.35 (2H, m), 7.18 (4H, m), 4.87 (1 H, d, J=12), 4.00-3.60 (5H, m), 3.60-3.10 (3H, m), 3.10-2.90 (2H, m), 1.45 (2H, m), 1.29 (4H, m), 1.15 (2H, m), 0.91 (3H, t. J=9), 0.83 (3H, t, J=9). MS (DCI/NH3) m/e 509 (M+H+). Anal calcd for C27H32F4N2θ3- 0.75 TFA: C, 57.62; H, 5.56; N, 4.72. Found: C, 57.72; H, 5.67; N, 4.66. Example 380 frans. frans-4-(f3.4-DimethvlPhenvn-2-f4-methoxvphenvn- 1 -f^N .N- dibutylamino^carbonyhmethvnpyrrolidine-3-carboxyiic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CDCI3 ) δ 7.43 (2H, d, J=9), 7.25 (1 H, bs), 7.18 (1 H, dd, J=8, 3), 7.1 1 (1 H, d, J=9), 6.90 (2H, d, J=10), 5.48 (1 H, d, J=12), 4.26 (IH, d. J=18), 4.16 (2H, m), 3.83 (2H, m), 3.81 (3H, s), 3.56 (1 H, bd, J=18), 3.37 (1 H, m), 3.20 (1 H, m), 2.96 (2H, m), 2.24 (3H, s), 2.22 (3H, s), 1.47 (2H, m), 1.27 (4H, m), 1.10 (2H, m), 0.93 (3H, t, J=9), 0.81 (3H, t, J=9). MS (DCI/NH3) m/e 495 (M+H+). Anal calcd for C30H42N2O4- 1.25 TFA: C, 61.26; H, 6.84; N, 4.40. Found: C, 61.16; H, 7.05; N, 4.38. Example 381 frans.frans-2.4-Dif3-fluoro-4-methoxyphenyn- 1 -(.f(N.N- dibutylaminotearbonvnmethvl )pvrrolidine-3-carboxvlic acid Using the procedures described in Example 1 , the title compound was prepared. H NMR (300MHz, CDCI3 ) δ 7.20 (2H, m), 7.17 (2H, m), 6.93 (2H, m), 5.48 (1 H, m), 4.26 (1 H, m), 4.16 (2H, m), 3.83 (2H. m), 3.87 (6H, s), 3.56 (1 H, m), 3.37 (1 H, m), 3.20 (1 H, m), 2.96 (2H, m), 1.47 (2H, m), 1.27 (4H, m), 1.10 (2H, m), 0.93 (3H, t, J=9), 0.81 (3H, t, J=9). MS (DCI/NH3) m/e 533 (M+H+). Anal calcd for C29H38F2N205- 0.75 H2O: C, 63.78; H, 7.29; N, 5.13. Found: C, 63.77; H, 7.08; N, 4.99. Example 382 frans. frans-4-f 1 .3-Benzodioxol-5-vn-2-(4-methoxvphenvl )- 1 -ff fN-f2- pentyn .N-f3-methylphenyl )amino^carbonvhmethvnpyrrolidine-3- carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CD3OD) δ 0.90 (m, 3H), 0.95 (t, J=7.3 Hz, 3H), 1.13-1.37 (m, 4H), 2.30 (s, 3H), 2.34 (s (CH3 rotamer)), 2.73- 2.91 (m, 2H), 3.17-3.26 (m, 2H), 3.32-3.62 (m, 2H), 3.77-4.08 (m, 1 H), 3.80 (s, 3H), 4.71 (m, 1 H), 5.92 (m, 2H), 6.61-6.84 (m, 6H), 7.04-7.16 (m, 3H), 7.23-7.29 (m, 2H). MS (DCI) m/e 559 (M+H+). Anal calcd for C33H38N2O6 ■ 0.35 H2O ■ 0.05 CH3CO2C2H5: C, 70.03; H, 6.92; N, 4.92. Found: C, 70.08; H, 6.82; N, 4.95. Example 383 trans. trans-4-( \ .3-Benzodioxol-5-yπ-2-(:4-methoxyphenvh-1 -.fN- butyl-N-M -naphthynaminocarbonylmethvhpyrrolidine-3-carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CD3OD) δ 0.87 (t, J=7 Hz, 3H), 1.20- 1.40 (m, 2H), 1.40-1.60 (m, 2H), 2.42-2.80 (m, 2H), 2.85-4.00 (m, 6H), 3.77 (d, J=1.5 Hz, 3H), 4.05-4.20 (m, 1 H), 5.94 (d, J=2 Hz, 2H), 6.6 (dd, J=9, 10 Hz, 1 H), 6.70-6.85 (m, 4H), 6.95-7.02 (m, 2H), 7.17 (dd, 8H, 1/2), 7.25 (dd, 8H, 1/2), 7.38-7.60 (m, 4H), 7.87-8.00 (m, 2H). MS (E.S.I.) m/e (M+H) 581. Analysis calcd for C35H36N2O6 ■ 1.4 H2O: C, 69.38; H, 6.45; N, 4.62. Found: C, 69.36; H, 6.07; N, 4.41. Example 384 frans.frans-2-f4-Methoxyρhenvn-4- 1 .3-benzodioxol-5-vn-1 -r2-fN- phenyl-N-n-hexanesulfonylamino thyllDyrrolidine-3-carboxylic acid Using the procedures described in Example 66, the title compound was prepared and isolated as a tan solid, m.p. 67-68 °C 1 H NMR (CD3OD, 300 MHz) δ 0.88 (t, J=7Hz. 3H), 1.25-1.40 (m, 6H), 1.73 (quintet, J=7Hz, 2H), 2.13-2.23 (m, 1 H). 2.64-2.88 (m, 3H), 3.02 (sextet, J=8Hz, 2H), 3.44-3.53 (m, 2H), 3.58 (d, J=9Hz, 1 H), 3.56-3.75 (m, 1H), 3.78 (s, 3H), 3.88-3.98 (m, 1 H), 5.93 (s, 2H), 6.72 (d, J=9Hz, 1 H). 5.78- 5.84 (m, 3H), 6.96 (d, J=2Hz, 1 H), 7.20 (d, J=9Hz, 2H), 7.27-7.36 (m, 5H). MS (DCI/NH3) m/e 609 (M+H)+. Example 385 frans. frans-4-M .3-Benzodioxol-5-vl ) -2-r4-methoxy p henvn- 1 -f2- methyl- 1 .2.3.4-tetrahydroquinolin- 1 -vncarbonylmethvnpyrrolidine-3- carboxvlic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CD3OD) δ 1.03 (m, 3H), 1.10-1.45 (m, 1 H), 2.10-2.85 (m, 4H), 2.90-4.00 (m, 7H), 3.76 (s, 1.5H), 3.77 (s, 1.5H, isomer), 5.90 (m, 2H), 6.70-7.40 (m, 1 1 H). MS (DCI) m/e 529 (M+H)+. Analysis calcd for C31 H32N2O6 • 0.3 H2O: C, 69.73; H, 6.15; N, 5.25. Found: C, 69.74; H, 6.10; N, 5.01. Example 386 frans.frans-4-f 1 .3-Benzodioxol-5-vn-2- -methoxvphenvh- 1 -r3- butyl-heot-2-en-1 -vhpyrrolidine-3-carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CD3OD) δ 0.86 (t, J=7.0 Hz, 3H), 0.90 (t, J=7.0 Hz, 3H), 1.20-1.41 (m, 8H), 1.95-2.06 (m, 4H), 3.24 (d. J=11.0 Hz, 1 H), 3.51-3.59 (m, 3H), 3.60-3.71 (m, 1 H), 3.77-3.84 (m, 1 H), 3.81 (s. 3H), 4.45 (d, J=11.0 Hz, 1H), 5.52 (t, J=7.4 Hz, 1 H), 5.93 (s, 2H), 6.77 (d, J=8.1 Hz, 1 H), 6.87 (dd, J=1.8, 8.1 Hz, 1 H), 6.99 (m, 3H), 7.46 (m, 2H). MS (DCI) m/e 494 (M+H+). Anal calcd for C30H39NO5: C, 72.99; H, 7.96; N, 2.84. Found: C, 72.73; H, 7.89; N, 2.64. Example 387 trans, frans-2-f 3-Fluoro-4-methoxyphenyn-4-(: i .3-benzodioxol-5-vn- 1 -r2-tN-propy[-N-n-hexanesulfonvlaminoϊethvnpyrrolidine-3- carboxylic acid Using the procedures described in Example 66, the title compound was prepared and isolated as a white solid, m.p. 63-65 °C. 1 H NMR (CDCI3, 300MHz) b 0.82 (t, J=7Hz, 3H), 0.88 (t, J=6Hz, 3H), 1.23-1.47 (m, 6H), 1.44 (sextet, J=7Hz, 2H), 1.71 (quintet, J=6Hz, 2H), 2.24-2.34 (m, 1 H), 2.70-2.93 (m, 5H), 2.96-3.12 (m, 2H), 3.15-3.35 (m, 2H), 3.43 (dd, J=3Hz, J=9Hz, 1 H), 3.52-3.59 (m, 1 H), 3.66 (d, J=9Hz, 1H), 3.87 (s, 3H), 5.95 (s, 2H), 6.74 (d, J=8Hz, 1 H), 6.82 (d, J=8Hz, 1 H), 6.42 (t, J=8Hz, 1H), 6.96 (s, 1H), 7.12 (d, J=9Hz, 1 H), 7.17 (d, J=12Hz, 1H). MS (DCI/NH3) m/e 593 (M+H)+. Example 388 frans. frans-4-M .3-Benzodioxol-5-vn-2- l f4-methoxvphenyh-1 -/f3- pyridyhmethynpvrrolidine-3-carboxvlic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CD3OD) δ 2.87 (m, 2H), 3.04 (dd, J=3.2, 9.7 Hz, 1 H), 3.21 (d, J=13.7 Hz, 1 H), 3.51 (m, 1 H), 3.76-3.85 (m, 2H), 3.79 (s, 3H), 5.90 (m, 2H), 6.71 (m, 1 H), 6.79 (dd, J=1.7 Hz, 7.8H), 6.94 (m, 3H), 7.36-7.45 (m, 3H), 7.81 (m, 1 H), 8.39 (m, 1 H), 8.46 (dd, J=1.4 Hz, 1H). Anal calcd for C25H24N2O5 • 0.70 H2O • 0.05 CH3CO2C2H5: C, 67.34; H, 5.79; N, 6.23. Found: C, 67.31 ; H, 5.63; N, 5.90. Example 389 trans. trans-2-(n-Hexy\)-4-( \ .S-benzodioxol-S-vn- I YN. N- dibutylaminocarbonylmethyl)pyrrolidine-3-carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (CDCI3, 300 MHz) δ 0.82-1.00 (m, 9H), 1.20-1.40 (m, 12H), 1.45-1.60 (m, 4H), 1.70-1.90 (br m, 2H), 3.10-3.46 (m, 6H), 3.65 (t, J=10.8 Hz. 1 H), 3.76 (t, J=11.0 Hz, 1 H), 3.92-4.06 (m, 2H), 4.14-4.34 (m, 2H), 5.94 (s, 2H), 6.73 (d, J=8.1 Hz, 1 H), 6.79 (dd, J=8.1 , 1.8 Hz, 1H), 6.87 (d, J=1.8 Hz, 1H). MS(DCI/NH3) m/e 489 (M+H)+. Anal calcd for C28H44N2O5 ■ 0.9 TFA: C, 60.53; H, 7.65; N, 4.74. Found: C, 60.62; H, 7.69; N, 4.61. Example 390 frans. frans-4-M ■3-Benzodioxol-5-vh-2- ( 4-methoxyphenvn- 1 - (N-(:2- pentvh-N-(4-fluoro-3- methylphenvhamino carbonvπmethvπpyrrolidine-3-carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CD3OD) δ 0.92 ( , 3H), 0.97 (t, J=7.1 Hz, 3H), 1.13-1.40 (m, 4H), 2.22 (m, 3H), 2.58-2.74 (m, 1 H), 2.78-2.87 (m, 1 H), 3.09-3.25 (m, 2H), 3.39-3.60 (m, 2H), 3.70-3.90 (m, 1 H), 3.80 (s, 3H), 4.70 (m, 1 H), 5.93 (m, 2H), 6.70-6.76 (m, 1 H), 6.75 (dd, J=1.4, 8.1 Hz, 1H), 6.80-6.94 (m, 4H). 6.96-7.13 (m, 4H). MS (DCI.) m/e 577 (M+H+). Anal calcd for C33H37FN2O6 • 0.25 H2O: C, 68.20; H, 6.50; N, 4.82. Found: C, 68.21 ; H, 6.46; N, 4.74. Example 391 frans.frans-4-π .3-Benzodioxol-5-vn-2-f4-methoxv p henvn-1 - .2- pyridyhmethvnpvrrolidine-3-carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CD3OD) δ 2.97 (dd, J=7.9, 9.7 Hz, 1 H), 3.04 (t, J=9.6 Hz, 1H), 3.18 (dd. J=4.4 Hz, 9.9H), 3.47 (d, J=14.0 Hz, 1 H), 3.59 (m, 1 H), 3.78 (s, 3H), 3.96 (d, J=9.9 Hz, 1 H), 3.97 (d, J=13.6 Hz, 1H), 5.90 (m, 2H), 6.73 (d, J=8.1 Hz, 1 H), 6.83 (dd, J=1.7, 7.9 Hz, 1 H), 6.92 (m, 2H), 6.96 (d, J=1.8 Hz, 1 H), 7.28 (m, 1H), 7.44 (m, 2H), 7.53 (d, J=8.1 Hz, 1 H), 7.80 (dt, J=1.8, 7.7 Hz, 1 H), 8.42 (m, 1 H). MS (DCI) m/e 433 (M+H+). Anal calcd for C25H24N2O5 ■ 0.35 H2O: C, 68.43; H, 5.67; N, 6.38. Found: C, 68.44; H, 5.61 ; N, 6.24. Example 392 trans. frans-2-(3-Phenylpropyh-4-M .3-benzodioxol-5-yn- 1 -ιf N.N- dibutylaminocarbonylmethvπ-pyrrolidine-3-carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (CDCI3, 300 MHz) δ 0.89-0.97 (m, 6H), 1.22-1.36 (m, 4H), 1.41-1.55 (m, 4H). 1.63-1.95 (m, 4H), 2.62 (dt, J=7.2, 2.1 Hz, 2H), 3.05-3.44 (m, 7H), 3.53-3.60 (m, 2H), 3.65-3.76 (m, 1 H), 3.82-3.90 ( , 1 H), 3.96-4.10 (m, 1 H), 5.92 (s, 2H), 6.71 (d, J=8.1 Hz, 1 H), 6.77 (dd, J=8.1 , 1.5 Hz, 1 H), 6.86(d, J=1.2 Hz, 1 H), 7.10-7.28 (m, 5H). MS(DCI/NH3) m/e 523 (M+H)+. Anal calcd for C31 H42N2O5 • 0.6 TFA: C, 65.43; H, 7.26; N, 4.74. Found: C, 65.28; H, 7.29; N, 4.50. Example 393 frans-frans-2-ι , 4-Methoxv-3-fluorophenyh-4-f7-methoxy- 1 .3- benzodioxol-5-vh- 1 -r( , N .N-dif n- butynamino^carbonylmethvnpyrrolidine-3-carboxylic acid Using the procedures described in Example 1 , the title compound was prepared and isolated as a white solid, m.p. 115-1 17 °C 1 H NMR (300 MHz, CDCI3) δ 0.82 (t, J=7Hz, 3H), 0.88 (t, J=7Hz, 3H), 1.05-1.5 (m, 8H), 2.85 (d, J=13Hz, 1 H), 2.90-3.17 (m, 5H), 3.20-3.35 (m, 1H), 3.35- 3.50 (m, 3H), 3.55-3.65 (m, 1 H), 3.84 (d, J=10Hz, 1 H), 3.87 (s, 3H), 3.92 (s, 3H), 5.94 (dd, J=4Hz, 2Hz. 2H), 6.62 (s, 1H), 6.70 (s, 1 H), 6.90 (t, J=8Hz, 1H), 7.05-7.20 (m, 2H). Example 394 frans-frans-2-M ■4-Benzodioxan-6-y -4-ι'7-methoxy-1 .3- benzodioxol-S-yπ- l -ftfN.N-dif n- butynamino arbonvlmethvnpvrrolidine-3-carboxylic acid o Using the procedures described in Example 1 , the title compound was prepared and isolated as a white solid, m.p. 107-110 °C 1 H NMR (300 MHz, CDCI3) δ 0.82 (t, J=7Hz, 3H). 0.88 (t, J=7Hz, 3H), 1.05-1.50 (m, 8H), 2.75 (d, J=13Hz, 1 H), 2.90-3.12 (m, 4H), 3.32-3.60 (m, 5H), 3.69 (d, J= 8Hz, 1 H). 3.90 (s, 3H), 4.23 (s, 4H), 5.95 (dd, J=4Hz, 2Hz, 2H), 6.62 5 (s, 1 H), 6.70 (s, 1H), 6.78-6.93 (m ,3H). Example 395 frans.frans-4-M .3-Benzodioxol-5-vπ-2-f4-methoxyρhenvh- 1 -f 3- butyl-2-fluoro-hept-2-en-1 -ynpyrrolidine-3-carboxylic acid 0 Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CD3OD) δ 0.84 (t, J=7.0 Hz, 3H), 0.88 (t, J=7.0 Hz, 3H), 1.16-1.37 (m, 8H), 1.83 (t, J=8.5 Hz, 2H), 2.03-2.08 (m, 2H), 2.76-2.92 (m, 2H), 3.02 (t, J=9.3 Hz, 1 H), 3.32-3.42 (m, 2H), 3.50 (m, 1 H), 3.71 (d, J=9.2 Hz, 1 H), 3.78 (s, 3H), 5.91 (m, 2H), 6.72 (d, 5 J=7.8 Hz, 1H), 6.83 (dd, J=1.7, 8.1 Hz. 1 H). 6.90 (m, 2H), 7.02 (d, J=1.7 Hz, 1 H), 7.34 (m, 2H). MS (DCI) m/e 512 (M+H+). Anal calcd for C30H38FNO5: C, 70.43; H, 7.49; N, 2.74. Found: C, 70.58; H, 7.54; N, 2.66. 0 Example 396 frans. frans-2-('3-Fluoro-4-ethoxyphenvn-4-π .3-benzodioxol-5-yπ- 1 - r2-(N-propyl-N-n-pentanesulfonylamino ethvnpyrrolidine-3-carboxylic Using the procedures described in Example 66, the title compound 5 was prepared and isolated as a white solid, m.p. 65-66 °C 1 H NMR (CDCI3, 300 MHz) δ 0.82 (t, J=7Hz, 3H), 0.90 (t, J=7Hz, 3H), 1.26-1.36 (m, 4H), 1.41-1.52 (m, 5H), 1.73 (quintet, J=7Hz, 2H), 2.23-2.33 (m, 1 H), 2.69-2.96 (m, 5H), 2.97-3.12 (m, 2H), 3.16-3.37 (m, 2H), 3.43 (d, J=9Hz, 1 H), 3.52-3.59 (m, 1H), 3.66 (d, J=9Hz, 1 H), 4.08 (q, J=7Hz, 2H), 5.95 (s, 2H), 6.74 (d, J=8Hz, 1 H), 6.82 (d, J=8Hz. 1 H), 6.92 (t, J=8Hz. 1 H), 6.97 (s. 1H), 7.07 (d. J=8Hz, 1H), 7.15 (d, J=12Hz, 1 H). MS (DCI/NH3) m/e 593 (M+H)+. Example 397 frans. frans-2-.f4-Methoxv-3-fluorophenyπ-4-(7-methoxy-1 .3- benzodioxol-5-vh-1 -r(;N-butyl-N- propylamino)carbonylmethvnpyrrolidine-3-carboxylic acid Using the procedures described in Example 1 , the title compound was prepared and isolated as a white solid, m.p. 118-120 °C. 1 H NMR (300 MHz, CDCI3) δ 0.70-0.90 (4 triplets, J=7Hz), 1.05-1.55 (m, 8H), 2.80-3.50 (m, 9H), 3.55-3.65 (m, 1 H), 3.82 (d, J= 10Hz. 1 H), 3.85 (s, 3H), 3.92 (s, 3H), 5.96 (s, 2H), 6.62 (s, 1 H), 6.70 (s, 1 H), 6.90 (t, J=8Hz, 1H), 7.08-7.22 (m, 2H). Example 398 frans. frans-4-M .3-benzodioxol-5-y I V2-(4-methoxyphenvπ- 1 -(f N- butyl-N-f4-chlorophenvnaminocarbonvlmethvnpyrrolidine-3- carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CD3OD) δ 0.87 (t, J=7 Hz, 3H), 1.20- 1.50 (m, 4H), 2.66-4.00 (m, 9H), 3.81 (s, 3H), 5.95 (s, 2H), 6.77 (d, J=7 Hz, 1H), 6.85 (d, J=8 Hz, 3H), 7.05 (m, 5H), 7.33-7.42 (m, 2H). MS (CI,) m/e 565 (M+H). Analysis calcd for C31 H33N2O6CI ■ 0.25 H3PO4: C, 63.16; H, 5.77; N, 4.75. Found: C, 63.14; H, 5.59; N, 4.53. Example 399 trans. trans-4-( λ ■3-Benzodioxol-5-yh-2- -methoxyphenvh- 1 -f4- methyl-1 .2.3.4-tetrahydroouinolin-1 -yncarbonylmethvhPyrrolidine-3- carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CD3OD) δ 1.27 (d, J=7 Hz, 1.5H), 1.28 (d, 7H, 1.5-diastereomer), 1.39-1.55 (m, 1 H), 2.02-2.15 (m, 1 H), 2.60- 3.25 (m, 5H), 3.33-4.00 (m, 5H), 3.78 (s, 3H), 5.92 (d, J=3 Hz, 2H), 6.73 (dd, J=8 Hz, 1 H), 6.75-6.90 (m, 3H), 6.91-7.35 (m, 7H). MS (DCI) m/e 529 (M+H)+. Analysis calcd for C31 H32N2O6: C, 70.44; H, 6.10; N, 5.30. Found: C, 70.16; H, 6.04; N, 5.04. Example 400 frans.frans-2-ιf3-Fluoro-4-methoxvPhenvh-4-M .3-benzodioxol-5-vn- 1 -[2-f N-propyl-N-.2-ι piperidin-1 - ynethanesulfonylamino^ethyHpyrrolidine-3-carboxylic acid Using the procedures described in Example 66, the title compound was prepared and isolated as a white solid, m.p. 95-96 °C 1 H NMR (CDCI3, 300MHz) δ 0.82 (t, J=7Hz, 3H), 1.43-1.55 (m, 4H), 1.63-1.72 (m, 4H), 2.29-2.38 (m, 1 H), 2.64-2.78 (m, 5H), 2.87 (t, J=8Hz. 1 H), 2.95- 3.04 (m, 5H), 3.20-3.30 (m, 1 H), 3.32-3.43 (m, 4H), 3.54-3.63 (m, 1H), 3.78 (d, J=8Hz, 1H), 3.87 (s, 3H), 5.92 (s, 2H), 6.72 (d, J=8Hz, 1 H), 6.78 (dd, J=2Hz, J=8Hz, 1H), 6.88 (t, J=8Hz, 1H), 6.94 (d, J=2Hz, 1H), 7.08- 7.20 (m, 2H). MS (DCI/NH3) m/e 620 (M+H)+. Example 401 frans.frans-2-tn-Heptvn-4-M .3-benzodioxol-5-yn- 1 -(N .N- dibutylaminocarbonylmethyl )pyrrolidine-3-carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. H NMR (CDCI3, 300 MHz) δ 0.83-0.98 (s, 9H), 1.18-1.40 (m, 14H), 1.44-1.60 (m, 4H), 1.72-1.96 (br m, 2H), 3.12-3.45 (m, 6H), 3.65 (t, J = 10.5 Hz, 1 H), 3.76 (t, J = 11.2 1 H), 3.90-4.06 (m, 2H), 4.13- 4.33 (m, 2H), 5.93 (s, 2H), 6.73 (d, J = 7.8 Hz, 1 H), 6.79 (dd, J = 7.8, 1.7 Hz, 1 H), 6.87 (d, J = 1.7 Hz, 1 H). MS(DCI/NH3) m/e 503 (M+H)+. Anal calcd for C29H46N2O5 • 0.75 TFA: C, 62.28; H, 8.01 ; N, 4.76. Found: C, 62.20; H, 7.99; N, 4.50. Example 402 frans. frans-4-n .3-Benzodioxol-5-vn-2-ιf4-methoxvphenvh- 1 -r3- methyl-1.2.3.4-tetrahydroquinolin-1 -vncarbonylmethyhpyrrolidine-3- carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CD3OD) δ 0.99 (d, 1.5H), 1.03 (d, J=6 Hz, 1.5H, second diastereomer), 2.60-4.00m (12), 3.78 (s, 1.5H), 3.79 (s, 1.5H, second diastereomer), 5.92 (s, 1 H), 5.93 (s, 1 H, diastereomer), 6.65-7.40 (m, 11 H). MS (DCI) m/e 529 (M+H)+. Analysis calcd for C31 H32N2O6 ■ 0.8 H2O: C, 68.57; H, 6.24; N, 5.16. Found: C, 70.44; H, 6.10; N, 5.30. Example 403 frans. frans-4-M .3-Benzodioxol-5-vn-2-f4-methoxyphenvn- 1 -( < N- butyl-N-r4-fluorophenvhaminocarbonylmethvnpyrrolidine-3- carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. ^ H NMR (300 MHz, CD3OD) δ 0.87 (t, J=7 Hz, 3H). 1.2-1.47 (m, 4H), 2.7 (d, J=12 Hz, 1H), 2.80 (t, J=9 Hz, 1 H), 3.09 (t, J=9 Hz, 1 H), 3.25 (d, J=15 Hz, 1 H), 3.40-3.47 (m, 1 H), 3.49-3.65 (m, 3H), 3.75 (d, J=12 Hz, 1 H), 3.80 (s, 3H), 5.94 (s, 2H), 6.72-6.86 (m, 4H), 7.00-7.15 (m, 7H). MS (DCI) m/e 549 (M+H)+. Analysis calcd for C31 H33N2O6F • 0.4 H2O: C, 66.99; H, 6.13; N, 5.04. Found: C, 66.99; H, 5.94; N, 4.9g. Example 404 frans. frans-1 -/N-Butvl-N-f3-methvlphenvnaminocarbonvlmethvn-2- f4-methoxyphenvn-4-('5-benzofuranvnpvrrolidine-3-carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. ^ H NMR (300MHz, CDCI3) δ 7.66 (1 H, bs), 7.60 (1 H, d, J=3Hz), 7.45 (2H, s), 7.15 (4H, m), 6.75 (5H, m), 3.96 (1 H, d, J=10Hz), 3.78 (3H, s), 3.74 (1 H, m), 3.59 (3H, ), 3.21 (1 H, t, J=9Hz), 3.19 (1 H, d, J=16Hz), 2.92 (1 H, t, J=9Hz), 2.70 (1 H, d, J=16Hz), 2.29 (3H, s), 1.41 (2H, m), 1.24 (2H, m), 0.85 (3H, t, J=7Hz). MS (DCI, NH3) m/e 541 (M+H+). Anal, calcd for C33H34N2O • 1 H2O: C, 71.21 ; H, 6.52; N 5.03. Found: C, 71.31 ; H, 6.30; N, 4.98. Example 405 frans. frans-1 -(N-Butyl-N-r3-methylphenynaminocarbonylmethvn-2- (4-fluorophenvn-4-(5-benzofuranvnpyrrolidine-3-carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CDCI3) δ 7.67 (1 H, bs), 7.60 (1 H, d, J=3Hz), 7.45 (2H, m), 7.18 (3H, m), 7.12 (1 H, d, J=7Hz), 6.93 (2H, m), 6.76 (1 H, d, =3Hz), 6.70 (2H, bd), 4.02 (1 H, m), 3.77 (1 H, m), 3.59 (3H, m). 3.29 (1 H, m), 3.19 (1 H, m), 2.94 (1 H, m), 2.71 (1 H, m), 2.30 (3H, s), 1.45 (2H, m), 1.26 (2H, sext, =7Hz), 0.84 (3H, t, =7Hz). MS (DCI, NH3) m/e 529 (M+H+). Anal, calcd for C33H34N2O5 • 0.2 HOAc: C, 71.98; H, 6.30; N 5.18. Found : C, 71.68; H, 5.89; N, 5.25. Example 406 frans.frans-4-n .3-Benzodioxol-5-vn-2-U-methoxyDhenvh-1 - fN. N- (di-f3-methylphenvhamino^carbonvπmethyπpyrrolidine-3-carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CD3OD) δ 2.27 (s, 6H), 2.81 (dd, J=8.1. 9.5 Hz, 1 H), 2.98 (d, J=15.3 Hz, 1 H), 3.20 (t, J=16.6 Hz, 1 H), 3.47-3.60 (m, 3H), 3.80 (s, 3H). 3.85 (d, J=9.5 Hz, 1 H), 5.91 (s, 2H), 6.73 (d, J=7.8 Hz, 1H), 6.85 (m, 3H), 6.95 (m, 4H), 7.05 (d, J=1.7 Hz, 1 H), 7.06-7.24 (m, 6H). MS (DCI) m/e 579 (M+H+). Anal calcd for C35H34N2O6 ■ 0.15 H2O • 0.20 CH3CO2C2H5: C, 71.79; H, 6.04; N, 4.68. Found: C, 71.81 ; H, 5.79; N, 4.51. Example 407 trans.trans-4-( \ .2-Dihydrobenzofuran-5-yπ-2- 4-methoxyphenyn-1 - ((f.fN-butyl-N-r3-methvlphenvnamino^carbonynmethyhpvrrolidine-3- carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H (300MHz, CDCI3 ) δ 7.73 (2H, m), 7.40-7.10 (4H, m), 6.92 (2H, m), 6.72 (2H, d, J=9), 6.63 (1 H, m), 5.40 (1 H, m), 4.55 (2H, t, J=9), 4.30-4.10 (3H, m), 3.84 (3H, s), 3.82 (1 H, m), 3.65 (1H, m), 3.39 (1 H, m), 3.21 (2H, t. J=9), 3.10-2.90 (2H, m), 2.26 (3H, s), 1.55 (2H, m), 1.45 (2H, m), 0.92 (3H, t, J=9). MS (DCI/NH3) m/e 543 (M+H+). Anal calcd for C33H38N2O5 • 0.65 H2O: C, 71.50; H, 7.15; N, 5.05 . Found: C, 71.47; H, 6.96; N, 4.83. Example 408 trans. frans-2- ( 3-Fluoro-4-methoxvphenvn-4-M .3-benzodioxol-5-vn- 1 - 2-rN-propvl-N-r2-rN. N- dimethylamino ethanesulfonvlamino ) ethvl}pyrrolidine-3-carboxylic acid Using the procedures described in Example 66, the title compound was prepared and isolated as a white solid, m.p. 81-82 °C 1 H NMR (CDCI3, 300 MHz) δ 0.80 (t, J=7Hz, 3H), 1.43 (sextet, J=7Hz, 2H), 2.15- 2.24 (m, 1 H), 2.36 (s, 6H), 2.66-2.76 (m, 1 H), 2.83-3.04 (m, 6H), 3.18- 3.41 (m, 5H), 3.55-3.63 (m, 1 H), 3.72 (d, J=8Hz, 1 H), 3.85 (s, 3H), 5.90 (d, J=6Hz. 2H). 6.67 (d, J=8Hz, 1 H), 6.78 (dd, J=2Hz, J=8Hz, 1 H), 6.84 (t, J=8Hz, 1H), 7.94 (d, J=2Hz, 1 H), 7.09 (d, J=8Hz, 1 H), 7.20 (dd, J=2Hz, J=12Hz, 1H). MS (DCI/NH3) m/e 580 (M+H)+. Example 409 trans. frans-1 -(N. N-Dibutylaminocarbonylmethvπ-2-ι / 4-f luorophenyh- 4-(5-benzofuranvhpyrrolidine-3-carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CDCI3) δ 7.88 (1 H, bs), 7.80 (2H, m), 7.61 (1 H, d, J=3Hz), 7.55 (1 H, bd. J=8Hz), 7.46 (1H, d, J=8Hz). 7.07 (2H. t, J=8Hz). 6.76 (1H, d. =3Hz), 5.53 (1 H, bd, J=11Hz), 4.18 (2H, m), 3.91 (3H, m), 3.55 (1 H, d, J=16Hz), 3.30 (3H, m), 3.12 (1 H, dd, J=10&9Hz), 2.95 (1H, m), 1.51 (2H, m), 1.31 (4H, m), 1.12 (2H, m), 0.92 (3H, m), 0.83 (3H, t, =7Hz). MS m/e (DCI, NH3) 595 (M+H+). Example 410 frans. frans-4-M .2-Dihvdrobenzofuran-5-vn-2-f4-ethvlphenvn- 1 -t:ffN- butyl-N-<f3-methylphenynamino^carbonvnmethynpyrrolidine-3- carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CDCI3 ) δ 7.35 (2H, m), 7.20-7.00 (7H, m), 6.70 (2H, d, J=9), 5.38 (1 H, m), 4.55 (2H, t, J=9), 4.05 (1 H, m), 3.64 (2H, m), 3.45 (1 H, m), 3.21 (2H, t, J=9), 2.95 (1H, m), 2.75 (1H, m), 2.63 (2H, q, J=8), 2.38 (2H, m), 2.27 (3H, s), 1.43 (2H, m), 1.30 (2H, m), 1.22 (3H, t, J=9), 0.89 (3H, t, J=9). MS (DCI/NH3) m/e 541 (M+H+). Anal calcd for C34H40N2O4 ■ 1.6 AcOH: C, 70.17; H, 7.34; N, 4.40. Found: C, 70.11 ; H, 7.06; N, 4.80. Example 411 frans.frans-4-π .2-Dihydrobenzofuran-5-yh-2-(4-fluorophenyn-1 - f7(N.N-dibutvlamino arbonvnmethvnpvrrolidine-3-carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CDCI3 ) δ 7.40 (2H, m), 7.28 (1H, bs). 7.18 (1H, dd, J=8, 3), 7.00 (2H, t, J=9), 6.72 (1H, d, J=9), 4.53 (2H, t, J=9), 3.92 (1 H, m), 3.65 (1 H, m), 3.42 (3H, m), 3.19 (2H, t, J=9), 3.15- 2.90 (6H, m), 1.43 (3H, m), 1.25 (3H, m), 1.10 (2H, m), 0.90 (3H, t. J=8), 0.83 (3H, t, J=8). MS (DCI/NH3) m/e 497 (M+H+). Anal calcd for C29H37FN2O4 ■ 0.25 H2O: C, 69.51 ; H, 7.54; N, 5.59. Found: C, 69.45; H, 7.60; N, 5.44. Example 412 frans.frans-4-M .2-Dihydrobenzofuran-5-vn-2-(4-fluorophenvn-1 - fιff N-butyl-N-f3-methylphenyπamino^carbonvπmethvπpyrrolidine-3- carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. " Η NMR (300 MHz, CDCI3 ) δ 7.28 (1 H, bs), 7.25-7.00 (5H, m), 6.91 (2H, m), 6.72 (3H, d, J=9), 4.54 (2H, t, J=9), 4.00 (1H. m), 3.60 (3H, m), 3.45 (1 H, m), 3.19 (2H, t, J=9), 3.11 (2H, m), 2.84 (1H, m). 2.67 (1H, bd, J=18), 2.26 (3H,s), 1.42 (2H, m), 1.25 (2H, ), 0.88 (3H, t, J=8). MS (DCI/NH3) m/e 531 (M+H+). Anal calcd for C32H35FN2O4 • 0.25 H2O: C, 71.82; H, 6.69; N, 5.23. Found: C, 71.66; H, 6.55; N, 5.03. Example 413 frans.frans-4-nndan-5-yπ-2-(4-methoxyphenyn- 1 -fιf ( N.N- dibutylamino^carbonyhmethynpyrrolidine-3-carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. H NMR (300 MHz, CDCI3 ) δ 7.32 (3H, ), 7.18 (2H, m), 6.85 (2H, d, J=9), 3.83 (1 H, m), 3.79 (3H, s), 3.67 (1H, m), 3.50-3.20 (4H, m), 3.20-2.92 (4H, m), 2.87 (5H, m), 2.79 (1 H, bd, J=15), 2.06 (2H, m), 1.43 (2H, m), 1.27 (4H, m), 1.08 (2H, m), 0.88 (3H, t, J=8), 0.82 (3H, t, J=8). MS (DCI/NH3) m/e 507 (M+H+). Anal calcd for C31 H42N2O4: C, 73.49; H, 8.36; N, 5.53. Found: C, 73.18; H, 8.29; N, 5.17. Example 414 frans.frans-2-f4-Methoxvphenvn-4-(3.4-difluorophenyh- 1 -ffN-btJtyl- N-f3-methvlPhenvnamino^carbonvlmethvi1pvrrolidine-3-carhoyylir acid Using the procedures described in Example 1 , the title compound was prepared. H NMR (300MHz, CDCI3) δ 0.86 (t, J=7Hz, 3H), 1.10-1.35 (m, 2H), 1.35-1.52 (m, 2H), 2.29 (s, 3H), 2.63 (d, J=13Hz, 1 H), 2.76 (t, J=7Hz, 1 H), 3.06-3.20 (m, 2H), 3.42-3.53 (m, 1 H), 3.50-3.64 (m, 3H), 3.80 (s, 3H), 3.86 (d, J=9Hz, 1 H), 6.66-6.82 (m, 4H), 7.02-7.22 (m, 6H), 7.30-7.40 (m, 1 H). Example 415 frans. frans-1 -rN-Butyl-N- 3-chloroDhenvnaminocarbonylmethyh-2- (4-fluorophenyn-4-(5-benzofuranvnpvrrolidine-3-carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CDCI3) δ 7.64 (1 H, d, J=2Hz), 7.61 (1H, d, J=3Hz), 7.47 (1 H, d, J=8Hz), 7.41 (1 H, dd, J=8&3Hz), 7.30 (1 H, dt, J=8&2Hz), 7.21 (1 H, d. J=8Hz), 7.19 (2H, m), 7.00 (1 H, bs), 6.94 (2H, t, =8Hz), 6.83 (1 H, bd, J=8Hz). 6.74 (1H, dd, J=2&1 Hz), 3.96 (1 H, d, 3.18 (1 H, d, J=16Hz), 2.92 (1 H, dd, J=10&9Hz), 2.69 (1 H, d, J=16Hz), 1.41 (2H, m), 1.23 (2H, m), 0.87 (3H. t, J=7Hz). MS (DCI, NH3) 549, 551 (M+H+). Anal, calcd for C31 H30CIFN2O: C, 67.82; H, 5.51 ; N, 5.10. Found: C, 67.43; H, 5.33; N, 4.78. Example 416 frans. frans-4-ι / 1 .3-Benzodioxol-5-yh-2- 4-methoxyphenyn- 1 -if ((N- propyl-N-f4-phenoxybenzvnamino)carbonyhmethynpyrrolidine-3- carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CDCI3 ) δ (rotamer) 7.40-7.20 (5H, m), 7.13 (2H, m), 6.98 (2H, m), 6.93-6.60 (7H, m), 5.93 (1 H, d. J=2), 5.88 (5.85) (1 H, d, J=2), 4.90 (4.50) (1 H, d, J=15), 4.10 (4.25) (1 H, d, J=15), 3.77 (3.73) (3H, s), 3.72 (1 H, m), 3.60 (1 H, m), 3.53-3.20 (3H, m), 3.15- 2.75 (4H, m), 1.60-1.20 (2H, m), 0.83 (0.64) (3H, t, J=8). MS (DCI/NH3) m/e 623 (M+H+). Anal calcd for C37H38N2O7 0.25 H2O: C, 70.85; H, 6.19; N, 4.47. Found: C, 70.68; H, 6.10; N, 4.42. Example 417 frans. frans-4-π .2-Dihvdrobenzofuran-5-vh-2-(4-ethvlPhenyn-1 -^. / N- (2-pent y n-N-(4-fluoro-3- methylphenvnamino^carbonyhmethvnpyrrolidine-3-carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CDCI3 ) δ 7.30 (1 H, bs), 7.20-7.00 (5H, m), 6.87 (1 H, m), 6.73 (2H, d, J=9), 6.57 (1 H, m), 4.81 (1 H, m), 4.55 (2H, t, J=9), 3.92 (1 H, bd, J=11), 3.60 (1 H, m), 3.43 (1 H, m), 3.18 (2H, t, J=9), 3.17 (1 H, m), 3.06 (1 H, dd, J=15, 6), 2.88 (1 H, dd, J=11 , 9), 2.61 (2H, q, J=8), 2.59 (1 H, m), 2.18 (3H. m). 1.40-1.10 (4H ,m). 1.22 (3H, t, J=9), 1.00-0.80 (6H, m). MS (DCI/NH3) m/e 573 (M+H+). Anal calcd for C35H41 FN2O4 O.75 H2O: C, 71.71 ; H, 7.31 ; N, 4.78. Found: C, 71.56; H, 7.33; N, 4.56. Example 418 frans. frans-2-ι / 4-Methoxphenvn-4-M .3-benzodioxol-5-yn- 1 -r2-(N- propyl-N-r2-pyrimidinvnamino^ethyl]pyrrolidine-3-carboxylic acid Ethyl 2-(4-methoxyphenyl)-4-(1 ,3-benzodioxol-5-yl)-1 -[2-(N- propylamino)propyl]pyrrolidine-3-carboxylate, prepared by the procedures of Example 61 B (300 mg), 138 mg of 2-bromopyrimidine, and 150 mg of diisopropylethylamine were heated at 95 °C for 15 hours in 2 mL of acetonitrile. The resulting intermediate trans-trans ethyl ester was isolated by chromatography on silica gel eluting with 5-10% ETOAc in CH2CI2 and hydrolyzed with NaOH in ethanol/water to give 95 mg of the title compound. 1 H NMR (300 MHz, CDCI3) δ 0.82 (t, J=7Hz, 3H), 1.50 (sextet, J=7Hz, 2H), 2.15-2.30 (m, 1 H), 2.75-2.97 (m, 3H), 3.40-3.55 (m ,4H), 3.60-3.70 (m, 3H), 3.75 (s, 3H). 5.95 (s, 2H), 6.34 (t, J=4Hz, 1H), 6.65 (d, J=8Hz, 1H), 6.75-6.82 (m, 1 H), 6.78 (d, J=9Hz, 2H), 6.96 (d, J=2Hz, 1 H), 7.27 (d, J=9Hz, 2H), 8.20 (d, J=4Hz, 2H). Example 419 frans.frans-4-M .3-Benzodioxol-5-vh-2-r4-methoxvnhβnvh- 1 -f 3- butyl-2-chloro-hept-2-en-1 -vl )Pvrrolidine-3-carboxvlir; arid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CD3OD) δ 0.84 (t, J=6.8 Hz, 3H), 0.88 (t, J=6.7 Hz, 3H), 1.19-1.39 (m, 8H), 2.05-2.09 (m, 2H), 2.17-2.23 (m, 2H), 2.78 (dd. J=6.6, 9.2 Hz, 1 H), 2.95 (t. J=9.2 Hz, 1 H), 3.32-3.37 (m. 2H), 3.49 (m, 1 H), 3.70 (d, J=9.2 Hz, 1 H), 3.77 (s, 3H), 5.91 (m, 2H), 6.72 (d, J=8.1 Hz, 1 H), 6.85 (dd. J=1.9, 8.1 Hz, 1 H), 6.89 (m, 2H). 7.08 (d. J=1.5 Hz, 1 H), 7.36 (m, 2H). MS (DCI) m/e 528 (M+H+). Anal calcd for C30H38CINO5 • 0.25 H2O: C, 67.66; H, 7.29; N, 2.63. Found: C, 67.62; H, 7.18; N, 2.40. Example 420 trans. frans-4-M .2-Dihydrobenzofuran-5-vh-2-f4-methoxyphenyl )-1 - (7/N-r2-pentvn-N-(4-fluoro-3- methylphenyhamino^carbonvhmethyπpyrrolidine-3-carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CDCI3 ) δ 7.28 (1 H, bs), 7.15 (3H, m), 6.90 (1 H. m), 6.77 (2H, dd, J=9, 3), 6.71 (2H, d, J=9), 6.56 (1H, m), 4.80 (1H, ). 4.53 (2H, t. J=9), 3.92 (1 H. m). 3.79 (3H. s), 3.60 (1 H, m), 3.45 (1H, m), 3.19 (2H, t, J=9), 3.18 (1 H, m), 3.03 (1 H, dd, J=15, 6), 2.85 (1 H, m), 2.55 (1 H, m), 2.18 (3H, m), 1.40-1.05 (4H, m), 1.00-0.80 (6H, m). MS (DCI/NH3) m/e 575 (M+H+). Anal calcd for C34H39FN2O5 • 0.35 H2O: C, 70.29; H, 6.89; N, 4.82. Found: C, 70.37; H, 6.92; N, 4.30. Example 421 frans.frans-4-M .2-Dihydrobenzofuran-5-vh-2-r4-methoxvphenyh-1 - dffN-butyl-N-<f3-chlorophenvnamino^carbonyπmethvnpyrrolidine-3- carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CDCI3 ) δ 7.29 (1 H, d, J=3), 7.25-7.05 (5H, m), 6.98 (1 H, bs), 6.80 (2H, m), 6.72 (2H, d, J=9), 4.53 (2H, t, J=9), 3.85 (1 H, d, J=10), 3.79 (3H, s), 3.58 (3H, m), 3.42 (1 H, dd, J=10, 6), 3.18 (4H, m), 2.87 (1 H, m), 2.66 (1 H, m), 1.40 (2H, m), 1.25 (2H, m), 0.86 (3H, t, J=9). MS (DCI/NH3) m/e 563 (M+H+). Anal calcd for C32H35CIN2O5 • 0.25 H2O: C, 67.72; H, 6.30; N, 4.94. Found: C, 67.72; H, 6.21 ; N, 4.55. Example 422 frans.frans-4-f 1 .3-Benzodioxol-5-vn-2-(5-ethvlfuran-2-yh-1 -(.f.fN.N- dibutylaminotearbonyπmethyπpyrrolidine-3-carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. " Η NMR (300 MHz, CDCI3 ) δ 7.77 (1H, bs), 7.11 (1H, d, J=3), 7.02 (1 H, dd, J=9, 3), 6.82 (1 H, d, J=9), 6.52 (1 H, d, J=4), 6.08 (1 H, d, J=4), 5.98 (2H, s), 5.80 (1H, d, J=6), 4.70 (1 H, bd, J=15), 4.37 (2H, m), 3.70 (2H, m), 3.39 (2H, m), 3.20 (1 H, m), 3.10-2.82 (2H, m), 2.76 (2H, q, J=8), 1.45 (2H, m), 1.32 (3H, t, J=9), 1.30-1.10 (6H, m), 0.87 (3H, t, J=9), 0.85 (3H, t, J=9). MS (DCI/NH3) m/e 499 (M+H+). Anal calcd for C28H38N2O6 • 1.75 HCl: C, 59.80; H, 7.12; N, 4.98. Found: C, 59.51 ; H, 6.96; N, 4.88. Example 423 trans. frans-4-M .2-Dihydrobenzofuran-5-yπ-2-.f4-fluorophenyh-1 - ( • ( • (NY2-pentvn-N-f4-fluoro-3- methylphenvπamino carbonyπmethyhpyrrolidine-3-carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CDCI3 ) δ 7.30-7.10 (4H, m), 6.92 (3H, m), 6.73 (2H, d, J=9), 6.59 (1 H, m), 4.80 (1 H, m), 4.53 (2H. t, J=9), 4.00 (1H, bd, J=10), 3.62 (1H, m), 3.45 (1H, m), 3.22 (1 H, m), 3.21 (2H, t, J=9), 3.02 (1 H, dd, J=15, 6), 3.85 (1 H, t, J=10), 2.58 (1 H, bd, J=18), 2.20 (3H, bs), 1.40-1.30 (3H, m), 1.15 (1 H, m), 1.00-0.80 (6H, m). MS (DCI/NH3) m/e 563 (M+H+). Anal calcd for C33H36 2N2O4: C, 70.44; H, 6.45; N, 4.98. Found: C, 70.06; H, 6.47; N, 4.71. Example 424 frans. frans-4-M .2-Dihydrobenzofuran-5-yh-2-f:4-fluorophenyh-1 - (((N-butyl-N-(3-chlorophenynamino)carbonyhmethyl )pyrrolidine-3- carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CDCI3 ) δ 7.30 (2H, m), 7.25-7.10 (4H, m), 6.95 (3H, m), 6.82 (1 H, bd, J=9), 6.73 (1 H, d, J=9), 4.55 (2H, t, J=9), 3.g2 (1H, bd, J=11), 3.60 (3H, m), 3.43 (1H, dd, J=g, 6), 3.21 (2H, t, J=9), 3.16 (2H, m), 2.87 (1H, m).2.69 (1H, m), 1.42 (2H, m), 1.26 (2H, m), 0.87 (3H, t, J=9). MS (DCI/NH3) m/e 551 (M+H+). Anal calcd for C31H32CIFN2O4 • 0.25 H2O: C, 67.02; H, 5.90; N, 5.04. Found: C, 66.98; H, 5.71; N, 4.76. Example 425 frans.frans-4-n.2-Dihvdrobenzofuran-5-yn-2- 4-ethylphenvh-1-ttfN- butyl-N-f3-chlorophenynamino^carbonynmethvnpyrrolidine-3- carboxylic acid Using the procedures described in Example 1, the title compound was prepared. 1 H NMR (300 MHz, CDCI3 ) δ 7.30 (1H, m), 7.21 (1H, d, J=9), 7.15 (2H, m), 7.09 (4H, bs), 6.96 (1H, bs), 6.80 (1H, bd, J=9), 6.73 (1H. d, J=9), 4.54 (2H, t, J=9).3.89 (1H, bd, J=11), 3.60 (3H. m), 3.43 (1H, m), 3.22 (2H, t, J=9).3.18 (2H, m), 2.92 (1H, m), 2.72 (1H, m), 2.62 (2H, q, J=8). 1.41 (2H, m), 1.26 (2H, m), 1.23 (3H, t, J=9), 0.87 (3H, t, J=9). MS (DCI/NH3) m/e 561 (M+H+). Anal calcd for C33H37CIN2O4 • 0.25 H2O: C, 70.08; H, 6.68; N, 4.95. Found: C, 70.13; H, 6.59; N, 4.65. Example 426 frans.frans-1-rN-Butyl-N-f3-chlorophenvncarboxamidomethyn-2-r4- methoxyphenyn-4-f5-benzofuranvnpyrrolidine-3-carboxylic acid Using the procedures described in Example 1, the title compound was prepared. 1 H NMR (300 MHz, CDCI3) δ 7.67 (1H, bs), 7.60 (1H, d, J=3Hz), 7.48 (1H, d, =8Hz), 7.42 (1H, dd, J=8&3Hz), 7.29 (1H, dt, J=8&3Hz), 7.21 (1H, d, =8Hz), 7.14 (2H, m), 6.99 (1H, bs), 6.76 (4H, m), 3.88 (1H, d, J=10Hz), 3.75 (1H, ddd, J=6, 5&3Hz), 3.59 (2H, m), 3.53 (1H, dd, J=10&3Hz), 3.22 (1H, t, J=9Hz), 3.19 (1H, m), 2.96( 1H, m), 2.70 (1H, d, J=16Hz), 1.42 (2H, m), 1.26 (2H, m), 0.87 (3H, t, J=7 z). MS (DCI, NH3) m/e 563, 561 (M+H+). Anal, calcd for C32H33CIN2O5 ■ 0.5 H2O: C, 67.42; H, 6.01; N, 4.91. Found: C, 67.45; H, 5.82; N, 4.68. Example 427 frans. frans-4-π .3-Benzodioxol-5-yn-2-f4-methoxvphenyh- 1 -fιf fN- cyclohexyl-N-butylamino^carbonynmethyhpyrrolidine-3-carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CDCI3) (rotamer) δ 0.78 (0.86) (t, 3H, J=7Hz), 0.90-1.90 (envelope, 14H), 2.69 (2.80) (d, 1 H, J=12Hz), 2.9-3.8 (envelope, 10H), 3.78 (3.80) (s, 3H), 5.92 (s, 2H), 6.72 (d, 1H, J=9Hz) 6.86 (m, 3H) 7.03 (d, 1 H, J=6Hz), 7.34 (m, 2H). MS (DCI/NH3) m/e 537 (M+H)+. Anal, calc'd for C31 H40N2O6 • 1 H2O: C, 67.13; H, 7.63; N, 5.05. Found: C, 67.09; H, 7.34; N, 4.92. Example 428 frans. frans-4-(1 .3-Benzodioxol-5-yn-2- -ethvlPhenvn-1 -f N-f3- methylphenyπ-N-butylamino^carbonyhmethvπpyrrolidine-3-carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CDCI3) δ 0.86 (t, 3H, J=7Hz), 1.22 (t, 3H, J=7Hz), 1.25 (m, 2H), 1.43 (m, 2H), 2.26 (s, 3H), 2.6 (q, 2H, J=7Hz). 2.68 (d, 1 H. J=12Hz), 2.86 (t, 1 H, J=8Hz), 3.19 (q, 2H, J=7Hz), 3.44 (dd, 1 H, J= 3Hz.10Hz), 3.59 (m, 3H), 3.94 (d, 1 H, 9Hz), 5.92 (s, 2H), 6.75 (m, 3H), 6.86 (dd, 1H, J= 2Hz, 8Hz), 7.08 (m, 6H), 7.17 (t, 1 H, J= 8Hz). MS (DCI/NH3) m/e 543 (M+H)+. Anal, calc'd for C33H38N2O5 • 0.60 H2O: C, 71.61 ; H, 7.14; N, 5.06. Found: C, 71.57; H, 6.80; N, 4.87. Example 429 frans.frans-4-(Benzofuran-5-vπ-2- 4-ethylphenvn- 1 -f-f ( ' N-f3- methylphenyl)-N-butylamino)carbonyhmethyπpyrrolidine-3-carboxylic acjci Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CDCI3) δ 0.90 (t, 3H, J=7Hz), 1.30 (t, 3H. J=7Hz), 1.31 (m, 2H), 1.43 (m, 2H), 2.27 (s, 3H), 2.73 (q, 2H, J=7Hz), 3.15 (d, 2H, J=17Hz), 3.61 (t, 2H, J= 8Hz), 3.82 (m, 2H), 4.00 (t, 1 H, 12Hz), 4.26 (m, 2H), 5.53 (br d. 1 H), 6.54 (br s, 2H), 6.76 (d, 1 H, J= 2Hz), 7.14 (m, 3H), 7.28 (s, 1H), 7.40 (m, 3H), 7.48 (d, 1 H, J= 8Hz), 7.63 (d, 1 H, J=2Hz), 7.73 (s, 1H). HRMS. calc'd for C34H39N2O4 (M+H)+: 539.2910. Found: 539.2891 Example 430 frans. frans-4-M .4-Benzodioxan-6-vn-2-f4-ethvl p henyn- 1 -tttN-(3- methylphenvh-N-butylamino^carbonvhmethvhPyrrolidine-3-carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CDCI3) δ 0.87 (t, 3H, J=7Hz), 1.22 (t, 3H, J=7Hz), 1.24 (m, 2H), 1.42 (m, 2H), 2.30 (s, 3H), 2.61 (q, 2H, J=7Hz), 2.67 (d, 1 H, J=14Hz), 2.86 (t, 1 H, J= 8Hz), 3.18 (q, 2H, J=7Hz), 3.41 (dd, 1 H, J=4,10Hz), 3.59 (m, 3H), 3.93 (d, 1 H, J=10Hz), 4.25 (m, 4H), 6.74 (br s, 2H), 6.80 (d, 1 H, J=8Hz), 6.93 (dd, 1 H, J=2Hz,8Hz), 6.99 (d, 1 H, J=2Hz), 7.07 (m, 5H), 7.17 (t, 1H, J=8Hz). MS (DCI/NH3) m/e 557 (M+H)+. Anal. calc'd for C34H40N2O5 • 0.40 H2O: C. 72.42; H, 7.29; N, 4.97. Found: C, 72.49; H, 7.16; N, 4.62. Example 431 frans. frans-2-f 3-Fluoro-4-methoxvphenvh-4-(1 .3-benzodioxol-5-yn- 1 -r2-(f N-propyl-N-2-mesitylenesulfonylamino)ethyπpyrrolidine-3- carboxylic acid Using the procedures described in Example 66, the title compound was prepared and isolated as a white solid, m.p. 80-82 °C 1 H NMR (CDCI3, 300 MHz) δ 0.69 (t, J=7Hz, 3H), 1.37 (sextet, J=7Hz, 2H), 2.09- 2.17 (m, 1 H), 2.24 (s, 3H), 2.53 (s, 6H), 2.54-2.64 (m, 1 H), 2.73-2.86 (m, 2H), 3.02 (sextet, J=7Hz, 2H), 3.13-3.28 (m, 3H)), 3.44-3.53 (m, 1 H), 3.57 (d, J=9Hz, 1H), 3.89 (s, 3H), 5.94 (s, 2H), 6.74 (d, J=8Hz, 1 H). 6.78 (dd, J=2Hz, J=8Hz, 1 H), 6.85 (s, 2H), 6.92 (d, J=8Hz, 1 H), 9.94 (d, J=2Hz. 1H), 7.06 (d, J=8Hz, 1 H), 7.13 (dd, J=2Hz, J=12Hz, 1 H). MS (DCI/NH3) m/e 627 (M+H)+. Example 432 frans. frans-2-f 4-Methoxyphenyh-4-(3.4-difluorophenyn- 1 -frN-butyl- N-ιf3-chlorophenyhamino carbonylmethyllpyrrolidine-3-carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CDCI3) δ 0.86 (t, J=7Hz, 3H), 1.18-1.32 (m, 2H), 1.35-1.48 (m, 2H), 2.64 (d, J=13Hz, 1H), 2.71 (t, J= 7Hz, 1 H), 3.08-3.18 (m, 2H), 3.42-3.48 (m, 1 H), 3.53-3.64 (m, 3H), 3.77 (s, 3H), 3.80 (d, J=9Hz, 1 H), 6.73-6.85 (m, 3H), 6.94 (s, 1 H), 7.04-7.40 (m, 7H). Example 433 frans. frans-2-f3-Fluoro-4-methoxyphenyn-4-π .3-benzodiQxol-5-yn- 1 -f2-(N-propyl-N-t3-chloropropanesulfonynamino thvnpyrrolidine-3- carboxvlic acid Using the procedures described in Example 1 , the title compound o was prepared. 1 H NMR (CD3OD, 300 MHz) δ 0.80 (t, 3H, J=7), 1.47 (bd hex, 2H, J=8), 2.15 (pen, 2H, J=7), 2.32 (m, 1H), 2.7-3.2 (m, 8H), 3.46 (dd, 1 H, J=4, 10), 3.57 (m, 1H), 3.64 (t, 2H, J=6), 3.67 (d, 1 H, J=9), 3.86 (s, 3H), 5.92 (s, 2H), 6.74 (d, 1 H, J=8), 6.84 (dd, 1 H, J=2, 8), 6.96 (d, 1 H, J=2), 7.06 (t, 1 H, J=9), 7.18 (m, 2H). MS (DCI/NH3) m/e 585 (M+H; 5 35ci)+; 587 (M+H; 37ci)+. Ana) calcd for C27H34N2O7CIFS: C, 55.43; H, 5.86; N, 4.79. Found: C, 55.65; H, 5.81; N, 4.70. Example 434 frans. frans-2-ιf3-Fluoro-4-methoxyρhenyh-4-ιf 1 .3-benzodioxol-5-yl )- 0 1 - 2-(N-isobutyl-N-f3-chloroproρanesulfonyhamino^ethvhρyrrolidine- 3-carboxylic acid Using the procedures described in Example 66, the title compound was prepared. 1 H NMR (CD3OD, 300 MHz) δ 0.79 (d, 3H, J=7), 0.84 (d, 3H, J=7),1.68 (hept, 1 H, J=7), 2.18 (pen, 2H, J=7), 2.8-3.4 (m, 10H), 3.5-3.8 5 (m, 3H), 3.65 (t, 2H, J=6), 3.90 (s, 3H), 5.94 (s, 2H), 6.77 (d, 1 H, J=8), 6.87 (dd, 1H, J=2, 8), 6.99 (d, 1 H, J=2), 7.13 (t, 1H, J=9), 7.27 (m, 2H). MS (DCI/NH3) m/e 599 (M+H)+. Anal calcd for C28H36N2O7CIFS • 0.3 TFA: C, 54.24; H, 5.78; N, 4.42. Found: C, 54.19; H, 5.71 ; N, 4.01. 0 Example 435 frans. frans-2-Propoxymethyl-4-M .3-benzodioxol-5-yh- 1 -(N .N- dibutylaminocarbonylmethvOpyrrolidine-3-carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (CDCI3, 300 MHz) δ 0.87-0.98 (m, 9H), 1.21-1.39 5 ( . 4H), 1.43-1.57 (m, 4H), 1.58-1.70 (m, 2H), 3.13-3.29 (m, 4H), 3.34- 3.43 (m, 3H), 3.45-3.55 (m, 3H), 3.69 (dd, J = 10.2, 4.5 Hz, 1 H), 3.80- 4.20 (m, 4H), 5.93 (s, 2H), 6.73 (d, J = 7.8 Hz, 1 H), 6.84 (dd, J = 8.2, 1.7 Hz, 1H), 6.93 (d, J = 1.7 Hz, 1 H). MS(DCI/NH3) m e 477 (M+H)+. Anal calcd for C-26H40N2O6-0.50 TFA: C, 60.77; H, 7.65; N, 5.25. Found: C, 60.73; H, 7.74; N, 5.22. Example 436 frans. frans-2- ( 3-Fluoro-4-methoxvphenvπ-4-n .3-benzodioxol-5-yn- 1 -r2-f N- p ro p yl-N-f4-methvlbutanesulfonynamino ethyl1pyrrolidine-3- carboxylic acid o Using the procedures described in Example 66, the title compound was prepared and isolated as a white solid, m.p. 65-67 °C 1 H NMR (CDCI3, 300MHz) δ 0.82 (t, J=7Hz, 3H), 0.88 (d, J=5Hz, 6H), 1.46 (sextet, J=7Hz, 2H), 1.56-1.64 (m, 3H), 2.24-2.33 (m, 1 H), 2.68-2.93 (m, 5H), 2.98-3.12 (m, 2H), 3.15-3.35 (m. 2H), 3.43 (dd, J=3Hz, J=9Hz, 1 H), 3.52- 5 3.58 (, 1 H), 3.65 (d, J=12Hz, 1H), 3.87 (s, 3H), 5.95 (s, 2H), 6.73 (d, J=8Hz. 1 H), 6.82 (dd, J=2Hz, J=8Hz, 1 H), 6.92 (t, J=8Hz, 1 H), 6.97 (d. J=2Hz, 1 H). 7.10 (d, J=9Hz, 1 Hz) , 7.16 (dd, J=2Hz, J=12Hz, 1 H). MS (DCI/NH3) m/e 579 (M+H)+. 0 Example 437 frans. frans-2-f4-Methoxy-3-fluorophenvn-4-f7-methoxy-1 .3- benzodioxol-5-vn-1 -. r 2-fN-propyl-N-(n- pentanesulfonvnamino thvHpyrrolidine-3-carboxylic acid Using the procedures described in Example 66, the title compound 5 was prepared. 1 H NMR (300MHz, CDCI3) δ 0.81 (t, J=7Hz, 3H). 0.90 (t, J=9Hz, 3H), 1.25-1.35 (m, 4H). 1.44 (sextet, J=7Hz, 2H), 1.67-1.78 (m, 2H), 2.22-2.34 (m, 1H), 2.30-2.95 (m, 5H), 2.95-3.10 (m, 2H), 3.15-3.33 (m, 2H), 3.45 (dd, J=3Hz, 9Hz, 1 H), 3.47-3.56 (m, 1 H), 3.65 (d, J=9Hz, 1 H), 3.88 (s, 3H), 3.94 (s, 3H), 5.95 (s, 2H), 6.55 (s, 1 H), 6.65 (s, 1 H), 0 6.92 (t, J=7H, 1H), 7.11 (d, J=9Hz,1 H), 7.17 (d, J=12Hz, 1 H). Example 438 frans.frans-2-f3-Fluoro-4-methoxyphenvn-4-f 1 .3-benzodioxol-5-yn- 1 -r2-f N-proDVI-N-f2.2.3.3.3- pentafluoropropoxyethanesulfonynamino^ethvnpyrrolidine-3- carboxylic acid Using the procedures described in Example 66, the title compound was prepared and isolated as a white solid, m.p. 63-64 °C 1 H NMR (CDCI3, 300MHz) δ 0.82 (t, J=7Hz, 3H), 1.45 (sextet, J=7Hz, 2H), 2.24- 2.33 (m, 1 H), 2.70-2.82 (m, 1 H), 2.85-3.09 (m, 5H), 3.14-3.28 (m, 4H), 3.43 (dd, J=3Hz, J=9Hz, 1 H), 3.52-3.58 (m, 1 H), 3.65 (d, J=9Hz, 1 H), 3.87 (s, 3H), 3.92-3.98 (m, 3H), 5.94 (s, 2H), 6.74 (d, J=8Hz, 1 H), 6.82 (dd, J=2Hz, J=8Hz, 1H), 6.92 (t, J=8Hz, 1H), 6.97 (d, J=2Hz, 1H), 7.10 (d, J=9Hz, 1H), 7.17 (dd, J=2Hz, J=12Hz, 1 H). MS (DCI/NH3) m/e 685 (M+H)+. Example 439 trans. frans-2-f 1 .4-Benzodioxan-6-vn-4-f7-methoxy-1 ,3-benzodioxol- 5-yn-1 -r2-f N-propyl-N-f n-pentanesulfonvnamino)ethyπpyrrolidine-3- carboxylic acid Using the procedures described in Example 66, the title compound was prepared. 1 H NMR (CDCI3) δ 0.81 (t, J=7Hz, 3H), 0.90 (t, J=7Hz, 3H), 1.23-1.36 (m, 4H), 1.45 (sextet, J=7Hz, 2H), 1.65-1.78 (m, 2H), 2.20- 2.30 (m, 1 H), 2.30-2.95 (m, 5H), 2.95-3.10 (m, 2H), 3.15-3.35 (m, 2H), 3.42 (dd, J=3Hz, 9Hz, 1 H), 3.46-3.56 (m, 1H), 3.59 (d, J=9Hz, 1 H), 3.91 (s, 3H), 4.24 (s, 4H), 5.95 (s, 2H), 6.57 (s, 1 H), 6.68 (s, 1 H), 6.82 (d. J=8Hz, 1 H), 6.88 (dd, J=2Hz, 8Hz, 1H), 6.95 (d, J=2Hz, 1 H). Example 440 trans, frans-4-f 1 .3-Benzodioxol-5-vlY2-f4-methoxyphenvn-1 -f f fN- butyl-N-f4-methoxybenzvnamino^carbonynmethynpyrrolidine-3- carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CDCI3 ) δ (rotamer) 7.32 (1 H, d, J=10). 7.22 (1 H, m), 7.10 (1 H, d, J=9), 7.03 (6.98) (1 H, d, J=3). 6.90-6.80 (4H, m), 6.79 (2H, d. J=9), 6.77 (1H, t, J=8), 5.85 (2H, s), 4.92 (4.10) (1H, d, J=15), 4.42 (4.22) (1 H, d, J=15), 3.81 (1 H, m), 3.79 (3.78) (3H, s), 3.76 (3H, s). 3.62 (1 H, m), 3.43 (2H, m), 3.30-2.70 (5H, m), 1.42 (1 H, m), 1.23 (2H, m), 1.01 (1 H, m), 0.83 (0.75) (3H, t, J=8). MS (DCI/NH3) m/e 575 (M+H+). Anal calcd for C33H38N2O7 ■ 0.5 H2O: C, 67.91 ; H, 6.73; N, 4.80. Found: C. 67.78; H, 6.44; N. 4.55. Example 441 frans.frans-2-f3-Fluoro-4-methoxvDhenvl )-4-f 1 .3-benzodioxQl-5-yn. 1 -f2-fN-isobutyl-N-fpentanesulfonvlamino thvnpvrroliriinft-3- carboxylic acid Using the procedures described in Example 66, the title compound was prepared. H NMR (CD3OD. 300 MHz) δ 0.76 (d, 3H, J=7), 0.84 (d. 3H, J=7), 0.92 (t, 3H, J=7), 1.36 (m, 4H),1.70 (m, 3H), 2.90 (m, 2H), 3.02 (m, 2H), 3.1-3.8 (m, 7H), 3.84 (d, 2H. J=8), 3.91 (s, 3H), 5.96 (s, 2H), 6.80 (d. 1 H, J=8), 6.88 (dd, 1 H, J=2, 8), 7.00 (d, 1 H, J=2), 7.19 (t, 1 H. J=9). 7.35 (m. 2H). MS (DCI/NH3) m/e 593 (M+H)+. Anal calcd for C30H41 N2O7F • 0.5 TFA: C, 57.31 ; H, 6.44; N, 4.31. Found: C, 57.08; H, 6.15; N, 3.95. Example 442 frans. frans-4-f 1 .3-Benzodioxol-5-yn-2-f4-methoxyphenyn- 1 -f N- butyl-N-f3-fluorophenylamino)carbonvlmethvnpvrrolidine-3- carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CD3OD) δ 0.87 (t, J=7 Hz, 3H), 1.10- 1.30 (m, 4H), 2.70-2.90 (m, 2H), 3.13 (t, J=8 Hz, 1 H), 3.40-3.90 (m, 6H), 3.79 (s, 3H), 5.93 (s, 2H), 6.75 (d, J=8 Hz, 1 H), 6.80-7.20 (m, 9H), 7.40 (m, 1H). MS (DCI) m/e 549 (M+H)+. Anal calcd for C31 H33N2O6F • 0.8 H2O: C, 66.13; H, 6.19; N, 4.g8. Found: C, 66.21 ; H, 5.83; N, 4.84. Example 443 frans. frans-4-f 1 .3-Benzodioxol-5-y H-2-f4-f luorophenyn-1 -f N-butyl- N-f3-chlorophenylamino arbonylmethynpyrrolidine-3-carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CD3OD) δ 0.87 (t, J=7 Hz, 3H), 1.20- 1.50 (m, 4H), 2.65-2.85 (m, 2H), 3.05-3.85 (m, 7H), 5.93 (s, 2H), 6.75 (d, J=8 Hz, 1 H), 6.85 (dd, J=8 Hz, 1 H), 6.90-7.10 (m, 4H), 7.10-7.25 (m, 3H), 7.33-7.45 (m, 2H). MS (DCI) m/e 553 (M+H)+. Anal calcd for C30H30N2O5FCI: C, 65.16; H. 5.47; N, 5.07. Found: C, 65.37; H, 5.41 ; N, 4.98. Example 444 frans. frans-4-f 1 .3-Benzodioxol-5-y n-2-f 4-methoxy p henvn- 1 -f f f N- butyl-N-f3.4-dimethoxybenzvnamino carbonynmethvnpyrrolidine-3- carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CDCI3 ) δ (rotamer) 7.33 (1H, d, J=10), 7.23 (1 H, m), 7.03 (6.97) (1H, d, J=3), 6.90-6.60 (6H, m), 6.47 (1 H, m), 5.93 (2H, m), 4.83 (4.09) (1 H, d, J=15), 4.45 (4.22) (1 H, d, J=15). 3.83 (3.86) (3H. s). 3.79 (1H, m), 3.77 (3.76) (3H, s), 3.75 (3.65) (3H, s), 3.60 (1 H, m), 3.43 (2H, m), 3.28 (1 H, m), 3.20-2.70 (4H, m), 1.43 (1H, m), 1.23 (2H, m), 1.02 (1 H, m), 0.84 (0.77) (3H, t, J=8). MS (DCI/NH3) m/e 605 (M+H+). Anal calcd for C34H40N2O8: C, 67.53; H, 6.67; N, 4.63. Found: C, 67.28; H, 6.63; N, 4.38. Example 445 trans. trans-4-( \ .3-Benzodioxol-5-yn-2-f4-methoxyphenvn- 1 -f(f N- butyl-N-(2-methoxybenzynamino)carbonynmethvnpyrrolidine-3- carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CDCI3 ) δ (rotamer) 7.33 (1H, d, J=10), 7.11 (2H, m), 7.03 (1 H, dd, J=8, 3), 6.90-6.60 (7H, m), 5.93 (2H, m), 4.83 (4.15) (1H, d, J=15), 4.47 (4.30) (1H, d, J=15), 3.81 (1H, m), 3.78 (3.73) (3H, s), 3.72 (3H, s), 3.59 (1H, ), 3.43 (2H, m), 3.30 (1 H, m), 3.20-2.70 (4H, m), 1.42 (1H, m), 1.23 (2H, m), 1.01 (1 H, m), 0.83 (0.77) (3H, t, J=8). MS (DCI/NH3) m/e 575 (M+H+). Anal calcd for C33H38N2O7: C, 68.97; H, 6.66; N, 4.87. Found: C, 68.70; H, 6.56; N, 4.61. Example 446 frans.frans-4-f1.3-Benzodioxol-5-vn-2-f4-methoxyphenyn-1-fffN- butyl-N-f3-methoxybenzvnamino)carbonynmethvnpyrrolidine-3- carboxylic acid Using the procedures described in Example 1, the title compound was prepared. 1 H NMR (300 MHz, CDCI3 ) δ (rotamer) 7.31 (1H, d, J=10), 7.13 (1H, d, J=8), 7.16 (1H, dt, J=8, 3), 7.03 (1H, dd, J=10, 2), 6.90-6.60 (6H, m), 6.50 (1H, m), 5.84 (2H, m), 4.82 (4.ig) (1H, d, J=15), 4.50 (4.23) (1H, d, J=15), 3.78 (3.76) (3H, s), 3.77 (1H, m), 3.75 (3.67) (3H, s), 3.58 (1H, m), 3.57-3.35 (2H, m), 3.25 (1H, m), 3.20-2.70 (4H, m), 1.43 (1H, m), 1.23 (2H, m), 1.02 (1H, m), 0.84 (0.77) (3H, t, J=8). MS (DCI/NH3) m/e 575 (M+H+). Anal calcd for C33H38N2O7: C, 68.87; H, 6.66; N, 4.87. Found: C, 68.72; H, 6.55; N, 4.60. Example 447 frans. frans-2-f 3-Fluoro-4-methoxyphenyn-4-f1 ,3-benzodioxol-5-yn- 1-f2-fN-f2-methoxyethvn-N-f3- chloropropanesulfonynamino thynpvrrolidine-3-carboxylic acid Using the procedures described in Example 66, the title compound was prepared. 1 H NMR (CD3OD, 300 MHz) δ 2.15 (pen, 2H, J=7), 2.33 (m, 1H), 2.81 (m, 2H); 2.93 (t, 1H, J=9); 3.1-3.6 (m, 10H), 3.24 (s, 3H); 3.65 (t, 2H, J=6), 3.70 (d, 1H, J=9), 3.87 (s, 3H), 5.92 (s, 2H), 6.74 (d, 1H, J=8), 6.84 (dd, 1H, J=2, 8), 6.97 (d, 1H, J=2), 7.07 (t, 1H, J=9), 7.17 (m, 2H). MS (DCI/NH3) m/e 601 (M+H)+. Anal calcd for C-27H34N2O8CIFS: C, 53.95; H, 5.70; N, 4.66. Found: C, 53.65; H, 5.49; N, 4.26. Example 448 frans.frans-2-f3-Fluoro-4-methoxyphenvn-4-f1.3-benzodioxol-5-yn- 1-f2-fN-f2-methoxyethyn-N- (pentanesulfonvnamino thvnpyrrolidine-3-carboxylic acid Using the procedures described in Example 66, the title compound was prepared. " Η NMR (CD3OD, 300 MHz) δ 0.93 (m, 3H), 1.34 (m, 4H), 1.69 (m, 2H), 2.33 (m, 1H), 2.75-3.1 (m, 7H), 3.23 (s, 3H). 3.3-3.6 (m, 6H), 3.70 (d, 1H, J=9), 3.86 (s, 3H), 5.92 (s, 2H), 6.74 (d, 1H, J=8), 6.84 (dd, 1H, J=2, 8), 6.97 (d, 1H, J=2), 7.07 (t, 1H, J=9), 7.18 (m, 2H). MS (DCI/NH3) m/e 595 (M+H)+. Anal calcd for C29H39 2O8FS: C, 58.57; H, 6.61 ; N, 4.71. Found: C, 58.21 ; H, 6.29; N. 4.2g. Example 449 frans. frans-4-f 1 .3-Benzodioxol-5-vn-2-f4-methoxvphenyn-1 -ff fN-4- heptyh-N-f4-fl uoro-3- methylphenylamino ) carbonvnmethvnpyrrolidine-3-carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. H NMR (300 MHz, CD3OD) δ 0.89 (m, 6H), 1.18-1.36 (m, 8H), 2.15 (bs, 1.5 (CH3 rotamer)), 2.28 (bs, 1.5 (CH3 rotamer)), 2.64 (t, J=14.9 Hz, 1 H), 2.82 (m, 1 H), 3.07-3.29 (m, 2H), 3.32-3.41 (m, 1H), 3.53-3.60 (m, 1 H). 3.70-3.79 (m, 1 H), 3.79 (s, 3H), 4.68 (m, 1 H), 5.92 (m, 2H), 6.69-6.90 (m, 6H), 6.93-7.07 (m, 4H). MS (DCI) m/e 605 (M+H+). Anal calcd for C35H41. FN2O6: C, 69.52; H, 6.83; N, 4.63. Found: C, 69.31 ; H, 6.78; N, 4.35. Example 450 frans.frans-4-f 1 .3-Benzodioxol-5-yn-2-f4-methoxvphenyn- 1 -fff N-f 5- nonyh-N-f4-fluoro-3- methylphenynamino)carbonynmethynpyrrolidine-3-carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CD3OD) δ 0.81 -0.90 (m, 6H), 1.30 (m, 12H), 2.14 (s, 1.5 (CH3 rotamer)), 2.30 (s, 1.5 (CH3 rotamer)), 2.60 (t. J=14.8 Hz, 1H), 2.80 (m, 1 H), 3.09-3.24 (m, 2H), 3.33-3.42 (m, 1H), 3.50-3.55 (m, 1 H), 3.65-3.77 (m, 1 H), 3.79 (s, 3H), 4.64 (m, 1 H), 5.93 (m, 2H), 6.70-6.84 (m, 5H), 6.91-7.13 (m, 5H). MS (DCI) m/e 633 (M+H+). Anal calcd for C37H45FN2O6. C, 70.23; H, 7.17; N, 4.43. Found: C, 70.14; H, 7.13; N, 4.10. Example 451 frans. frans-4-f 1 .3-Benzodioxol-5-yn-2-f4-methoxyphenyn-1 -ff N-f 5- nonylaminotoarbonynmethynpyrrolidine-3-carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CD3OD) δ 0.80 (t, J=7.0 Hz, 3H), 0.84 (t, J=7.1 Hz, 3H), 1.15-1.55 (m, 12H), 2.88 (d, J=15.9 Hz, 1 H), 3.07 (m, 2H), 3.26 (d, J=16.3 Hz, 1 H), 3.36 (dd, J=4.4, 9.8 Hz, 1 H), 3.64 (m, 1 H), 3.76 (m, 1H), 3.7g (s, 3H), 3.gβ (d, J=8.5 Hz, 1 H), 5. 3 (m, 2H), 6.77 (d, J=7.8 Hz, 1 H), 6.85 (dd, J=1.7, 8.1 Hz, 1 H), 6.83 (m, 2H), 6.99 (d, J=1.7 Hz, 1H), 7.3g (m, 2H). MS (DCI) m/e 525 (M+H+). Anal calcd for C30H46 2O6 ■ 0.35 H2O: C, 67.86; H, 7.73; N, 5.28. Found: C, 67.87; H, 7.63; N, 5.11. Example 452 trans. trans-4-( .3-Benzodioxol-5-yn-2-f4-methoxyphenvn-1 -f/N- butyl-N-f2-fluorophenvnamino ) carbonylmethvnpyrrolidine-3- carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CD3OD) δ 0.87 (dt, J=7 Hz, 3H), 1.15- 1.32 (m, 4H), 3.77 (d, J=2 Hz, 3H), 2.65-5.92 (m, 9H), 5.93 (d, J=4 Hz, 2H), 6.70-6.90 (m, 4H). 7.00-7.45 (m, 7H). MS (DCI) m/e 549 (M+H)+. Anal calcd for C31 H33N2O6 • 0.4 H2O: C, 66.99; H, 6.13; N, 5.04. Found: C, 67.01 ; H, 6.23; N, 4.68. Example 453 trans, frans-2-f 4-Methoxphen vn-4-f 1 .3-benzodioxol-5-vn-1 -f2-f N- propyl-N-f2-benzothiazolynaminoϊethyπpyrrolidine-3-carboxylic acid The title compound was prepared by the method of Example 418, substituting 2-chlorobenzothiazole for 2-bromopyrimidine. 1 H NMR (300 MHz, CDCI3) δ 0.88 (t, J=7Hz, 3H), 1.59 (sextet, J=7Hz, 2H), 2.25- 2.37 (m, 1 H), 2.85-2.97 (m, 3H), 3.28-3.36 (m, 2H), 3.50-3.58 (m, 3H), 3.60-3.65 (m, 1 H), 3.67 (d, J=9Hz, 1 H),3.71 (s, 3H), 5.87 (d. J=2Hz, 1 H), 5.91 (d, J=2Hz, 1 H), 6.57 (d, J=8Hz, 1H), 6.73 (dd. J=2Hz, 9Hz, 1H), 6.76 (d, J=8 Hz, 2H), 6.91 (d, J=2Hz, 1 H), 7.01 (t, J=8Hz, 1 H), 7.22 (t, J=8Hz, 1 H), 7.29 (d, J=8Hz, 2H), 7.40 (d, J=7Hz, 1 H), 7.55 (d, J=7Hz, 1 H). Example 454 frans. frans-2-f2-Ethoxyethvn-4-f 1 .3-benzodioxol-5-yn- 1 -f N . N- dibutylaminocarbonylmethynpyrrolidine-3-carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (CDCI3, 300 MHz) δ 0.91 (t, J = 7.4 Hz, 3H), 0.94 (t, J = 7.4 Hz, 3H), 1.19 (t, J = 7.0 Hz, 3H), 1.24-1.38 (m, 5H), 1.46-1.60 (m, 4H), 2.03-2.12 (m, 2H), 3.07 (t, J = 8.0 Hz, 1 H), 3.07-3.34 (m, 6H), 3.43-3.52 (m, 3H), 3.59-3.74 (m, 3H), 3.80-4.01 (m, 2H), 5.93 (s, 2H), 6.72 (d, J = 8.1 Hz, 1H), 6.79 (dd, J = 8.2 Hz, 1.7 Hz, 1H), 6.87 (d, J = 1.7 Hz, 1H). MS(DCI/NH3) m/e 477 (M+H)+. Anal calcd for C26H40 2O6 • 0.4 TFA: C, 61.64; H, 7.80; N, 5.36. Found: C, 61.63; H, 7.84; N, 5.29. Example 455 frans. frans-2-f4-Methoxy-3-fluorophenyn-4-f 1 .3-benzodioxol-5-vn- 1 -r2-fN-propyl-N-f2-f morpholin-4- ylethvnsulfonylamino)ethyPpyrrolidine-3-carboxylic acid Ethyl 2-(4-methoxy-3-fluorophenyl)-4-(1 ,3-benzodioxol-5-yl)- 1 -[2-(N-propyl-N-[2-vinylsulfonyl]amino)ethyl]pyrrolidine-3- carboxylic acid, prepared by the procedures of Example 125, was reacted with excess morpholine for 4 hours at room temperature. Chromatography on silica gel eluting with EtOAc gave a 65% yield of an intermediate ethyl ester which was hydrolyzed to the title compound with NaOH in ethanol/water. 1 H NMR (300 MHz, CDCI3) δ 0.81 (t, J=7Hz, 3H), 1.46 (sextet, J=7Hz, 2H), 2.43-2.52 (m, 4H), 2.70-2.92 (m, 5H), 2.97-3.33 (m, 6H), 3.60 (dd, J=3Hz, 9Hz, 1 H), 3.51-3.59 (m, 1H), 3.62- 3.70 (m, 5H), 3.88 (s, 3H), 5.95 (s, 2H), 6.72 (d, J=8Hz, 1H), 6.70 (dd. J=2Hz, 8Hz, 1H), 6.90 (t, J=9Hz, 1H), 6.96 (d, J=2Hz, 1H), 7.10 (d, J=8Hz, 1H), 7.18 (dd, J=2Hz, 12Hz, 1 H). Example 456 frans. frans-2-f 3- Fluoro-4-methoxyphenyn-4-f 1 .3-benzodioxol-5-yn- 1 -r2-f N-proDvl-N-f (2.2.2- trifluoroethoxyethane^sulfonvnamino^ethyllpyrrolidine-3-carboxylic acid Using the procedures described in Example 66, the title compound was prepared and isolated as a white solid, m.p. 95-96 °C 1 H NMR (CD3OD, 300MHz) δ 0.80 (t, J=7Hz, 3H), 1.35-1.48 (m, 2H),3.07 (sextet, J=7Hz, 2H), 3.23-3.55 (m, 8H), 3.80-3.87 (m, 2H), 3.93 (s, 3H), 3.94- 4.02 (m, 4H), 4.66 (d, J=12Hz, 1 H), 5.96 (s, 2H), 6.83 (d, J=8Hz, 1H), 6.94 (d, J=8Hz, 1H),7.06 (d, J=2Hz, 1H), 7.23 (t, J=9Hz, 1H), 7.43 (d, J=gHz, 1H), 7.49 (dd, J=2Hz,J=12Hz, 1H). MS (DCI/NH3) m/e 635 (M+H)+. Example 457 frans. frans-4-f 1 .3-Benzodioxol-5-vn-2-f4-fluoroDhenyn-1 -f N-butyl- N-f3-methylphenynaminocarbonvlmethvnpvrrolidine-3-carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CD3OD) δ 0.87 (t, J=7 Hz, 3H), 1.20- 1.50 (m, 4H), 2.31 (s, 3H), 2.65-2.80 (m, 2H), 3.18 (t, J=7 Hz, 1 H), 3.25 (d, J=10 Hz, 1 H), 3.35-3.65 (m, 4H), 3.79 (d, J=10 Hz, 1 H), 5.93 (s, 2H), 6.74 (d, J=7 Hz, 1 H), 6.80-6.90 (m, 3H), 6.91-7.09 (m, 3H), 7.10-7.35 (m, 4H). MS (DCI) m/e 533 (M+H)+. Anal calcd for C31 H33N2O5F: C, 69.91 ; H, 6.25; N, 5.26. Found: C, 69.56; H, 6.26; N, 5.23. Example 458 frans.frans-2-f3-Fluoro-4-methoxvphenvn-4-f 1 .3-benzodioxol-5-vn- 1 -f2-fN-f2-methoxyethyn-N-f butanesulfonylamino^ethvnpyrrolidine- 3-carboxylic acid Using the procedures described in Example 66, the title compound was prepared. 1 H NMR (CD3OD, 300 MHz) δ 0.94 (m, 3H), 1.23 (hex, 2H, J=8), 1.69 (m, 2H), 3.08 (m,2H), 3.20 (s, 3H), 3.3-3.5 (m, 10H), 3.77 (m, 2H), 3.92 (s, 3H), 4.60 (m, 1 H), 5.96 (s, 2H), 6.81 (d, 1 H, J=8), 6.88 (dd, 1 H, J=2, 8), 6.99 (d, 1 H, J=2), 7.22 (t, 1 H, J=9), 7.38 (m, 2H). MS (APCI) m/e 581 (M+H)+. Anal calcd for C28H37N2O8FS - 1.1 TFA: C, 51.37; H, 5.44; N, 3.97. Found: C, 51.27; H, 5.35; N, 4.11. Example 459 trans, frans-2-f 3-Fluoro-4-methoxvphenvn-4-f 1 .3-benzodioxol-5-yn- 1 -r2-fN-proρyl-N-f2-methvlproDanesulfonvnamino^ethyl1pyrrolidine- 3-carboxylic acid Using the procedures described in Example 66, the title compound was prepared and isolated as a white solid, m.p. 77-78 °C. 1 H NMR (CDCI3, 300MHz) δ 0.83 (t, J=7Hz, 3H),1.06 (d, J=6Hz, 6H),1.45 (q, J=7Hz, 2H), 2.20 (septet, J=6Hz, 1 H), 2.26-2.36 (m, 1 H), 2.62-2.78 (m, 3H), 2.85-2.95 (m, 2H), 2.97-3.10 (m, 2H), 3.15-3.35 (m, 2H), 3.43 (dd, J=3Hz, J=9Hz, 1 H), 3.53-3.62 (m, 1 H), 3.66 (d, J=9Hz, 1 H), 3.88 (s, 3H), 5.95 (s, 2H), 6.74 (d, J=8Hz, 1 H), 6.82 (dd, J=2Hz, J=8Hz, 1 H), 6.92 (t, J=8Hz, 1H), 6.97 (d, J=2Hz, 1 H), 7.12 (d, J=9Hz, 1 H), 7.18 (dd, J=2Hz, J=12Hz, 1H). MS (DCI/NH3) m/e 565 (M+H)+. Example 460 frans.frans-4-f 1 .3-Benzodioxol-5-vn-2-f4-methoxv p henyn- 1 -f f (N- butyl-N-f4-nitrobenzynamino^carbonvnmethvnpyrrolidine-3- carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CDCI3 ) δ (rotamer) 8.11 (2H, m),7.32 (3H, dd, J=8, 2), 7.16 (7.07) (1 H, bd, J=10), 6.08 (6.94) (1H, d, J=2), 6.85 (2H, d, J=9), 6.83-6.70 (2H, m), 5.99 (5.97) (2H, d, J=2), 5.02 (4.18) (1 H, d, J=15), 4.63 (4.38) (1 H, d, J=15), 3.79 (3.77) (3H, s), 3.72 (1 H, d, J=10), 3.61 (1 H, m), 3.48 (1 H, bd, J=15), 3.43-3.20 (2H, m), 3.06 (2H, m), 2.90 (1H, m), 3.70 (1H, bd, J=14), 1.43 (1H, m), 1.23 (2H, m), 1.02 (1 H, m), 0.84 (0.78) (3H, t, J=8). MS (DCI/NH3) m/e 590 (M+H+). Anal calcd for C32H35N3O8: C, 65.18; H, 5.98; N, 7.13. Found: C, 65.89; H, 5.85; N, 6.85. Example 461 trans, frans-2-f 4-Ethylphenyn-4-f 3.4-difluorophenvn-1 -fN.N- dibutylaminocarbonylmethvnpyrrolidine-3-carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (CD3OD. 300 MHz) δ 0.78 (t, 3H, J=7), 0.87 (t, 3H, J=7), 1.02 (hex, 2H, J=7), 1.22 (t, 3H, J=7), 1.27 (m, 2H), 1.45 (m, 2H, J=7), 2.63 (q, 2H, J=7), 2.77 (d, 1 H, J=14), 2.94 (dd, 1 H, J=7, 9), 3.05 (m, 3H), 3.3-3.5 m, 3H), 3.44 (d, 1H, J=14), 3.66 (m, 1H), 3.75 (d, 1H, J=10), 7.20 (td, 2H, J=1 ,8), 7.22 (m, 2H), 7.32 (td, 2H, J=1 ,8), 7.43 (ddd, 1 H, J=2,8,12). MS (DCI/NH3) m/e 501 (M+H)+. Anal calcd for C29H38N2O3F2 • 0.6 H2O: C, 68.11 ; H, 7.73; N, 5.48. Found: C, 68.03; H, 7.53; N, 5.37. Example 462 frans. frans-4-f I . S-Benzodioxol-S-vn^-M-methoxyphenvn-l -fN- butyl-N^-fluoro-S-methylphenvnaminocarbonylmethvnpyrrolidine- 3-carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CD3OD) δ 0.87 (t, J=7 Hz, 3H), 1.20- 1.50 (m, 4H), 2.21 (d, J=2 Hz, 3H), 2.64 (d, J=14 Hz, 1 H), 2.75 (dd, J=10 Hz, 1H), 3.05 (t, J=7 Hz, 1 H), 3.25 (d, J=15 Hz, 1 H), 3.35-3.70 (m, 5H), 3.77 (s, 3H), 5.82 (s, 2H), 6.70-6.92 (m, 6H), 6.96-7.10 (m, 4H). MS (DCI) m/e 563 (M+H)+. Anal calcd for C32H35N2O6F ■ 0.5 H2O: C, 67.24; H, 6.35; N, 4.00. Found: C, 67.16; H, 6.06; N, 4.81. Example 463 frans.frans-4-f 1 .3-Benzodioxol-5-yn-2-f4-methoxyphenvn- 1 -fN- butyl-N-ff3-iso p ropvnphenvnamino^carbonvlmethvn-pyrrolidine-3- carboxylic acid o Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CD3OD) δ 0.87 (t, 3H), 1.17 (d, J=7 Hz, 6H). 1.20-1.50 (m, 4H), 2.63 (d, J=15 Hz, 1 H), 2.75 (t, J=7 Hz, 1 H), 2.85 (m, 1 H), 3.00 (t, J=7 Hz, 1H), 3.25 (d, J=15 Hz, 1 H), 3.40-3.70 (m, 5H), 3.75 (s, 3H), 5.80 (s, 2H), 6.65-6.80 (m, 3H), 6.71 (dt, J=7 Hz, 3H), 7.07 5 (m, 3H), 7.20-7.35 (m, 2H). MS (DCI) m/e 573 (M+H)+. Anal calcd for C34H40N2O6 • 0.15 H3PO4: C, 69.52; H, 6.94; N, 4.77. Found: C, 63.31 ; H, 6.72; N, 4.43. Example 464 0 frans.frans-4-f 1 .3-Benzodioxol-5-vn-2-f4-methoxvphenyn-1 -fN- butyl-N-f3-ethylphenynaminocarbonylmethvnpyrrolidine-3-carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CD3OD) δ 0.87 (m, J=7 Hz, 3H), 1.16 (t, 5 J=7 Hz, 3H), 1.20-1.47 (m, 4H), 2.50 (q, J=7 Hz, 2H), 2.70-2.85 (m, 2H), 3.13 (t, J=7 Hz, 1H), 3.20-4.5 (m, 6H), 3.78 (s, 3H), 3.83 (d, J=8 Hz, 1 H), 5.92 (s, 2H), 6.72 (d, J=8 Hz, 1H), 6.80-6.90 (m, 5H), 7.02-7.13 (m, 3H), 7.15-7.25 (m, 2H). MS (DCI) m/e 559 (M+H)+. Anal calcd for C33H38N2O6 • 0.3 H2O: C, 70.27; H, 6.90; N, 4.97. Found: C, 70.31 ; H, 0 6.63; N, 4.60. Examole 465 frans.frans-4-f1.3-Benzodioxol-5-vh-2-f4-ethvlphenvn-1-fffN-f3- chlorophenyn-N-butylamino^carbonvhmethynpyrrolidine-3-carboxylic acid Using the procedures described in Example 1, the title compound was prepared. 1 H NMR (300 MHz, CDCI3) δ 0.87 (t, 3H, J=7Hz), 1.23 (t, 3H, J=7Hz), 1.28 (m, 2H), 1.41 (m, 2H), 2.63 (q, 2H, J=7Hz), 2.67 (m, 1H), 2.92 (m, 1H), 3.20 (m, 2H), 3.42 (m, 1 H), 3.60 (q, 2H, J=7Hz), 3.93 (m, 1H), 5.92 (s, 2H), 6.75 (d, 1H, J=8Hz), 6.84 (m, 3H), 6.95 (br s, 1H), 7.02 (s, 1H), 7.10 (br s, 3H), 7.25 (m, 2H). MS (APCI) m/e 563 (M+H)+. Anal. calc'd for C32H35N2O5CI • 0.80 H3PO4: C, 59.92; H, 5.88; N, 4.37. Found: C, 59.gθ; H, 5.83; N, 4.07. Example 466 frans.frans-4-f1.4-Benzodioxan-6-vn-2-f4-ethylphenvn-1-fffN-f3- chlorophenyn-N-butylamino carbonvnmethynpyrrolidine-3-carboxylic add Using the procedures described in Example 1, the title compound was prepared. 1 H NMR (300 MHz, CDCI3) δ 0.86 (t, 3H, J=7Hz), 1.23 (t, 3H, J=7Hz), 1.25 (m, 2H), 1.40 (m, 2H), 2.64 (q, 2H, J=7Hz), 2.70 (m, 1H), 2.95 (m, 1H), 3.20 (m, 2H), 3.40 (m, 1 H), 3.57 (m, 3H), 3.90 (m, 1H), 4.25 (s, 4H), 6.80 (d, 1H, J=8Hz), 6.95 (d, 1H, J=2Hz), 6.95 (m, 2H), 7.07 (br s, 3H), 7.22 (m, 3H). MS (APCI) m/e 577. (M+H)+. Anal, calc'd for C33H37N2O5CI • 0.85 H2O: C, 66.90; H, 6.58; N, 4.73. Found: C, 66.92; H, 6.25; N, 4.36. Example 467 frans. frans-4-f Benzof uran-5-vn-2-f4-ethylphenvn-1-fffN-f 3- chlorophenyn-N-butylamino carbonvnmethvnpyrrolidine-3-carboxylic acid Using the procedures described in Example 1, the title compound was prepared. 1 H NMR (300 MHz, CDCI3) δ 0.85 (t, 3H, J=7Hz), 1.26 (t, 3H, J=7Hz), 1.30 (m, 2H), 1.40 (m, 2H), 2.60 (q, 2H, J=7Hz), 2.72 (m, 1H), 2.93 (m, 1H), 3.22 (m, 2H), 3.50 (m, 1H), 3.55 (m, 2H), 3.75 (m, 1H), 3.90 (br d, 1H), 6.75 (d, 1H, J=1Hz), 6.80 (br d, 1H), 6.95 (br s, 1H), 7.08 (m, 4H), 7.20 (t, 1H, J=8Hz), 7.28 (t, 1H, J=8Hz), 7.42 (m, 2H), 7.58 (d, 1H, J=1 Hz), 7.63 (s, 1 H). MS (APCI) m/e 559 (M+H)+. Anal, calc'd for C33H35N2O4CI • 0.45 H2O: C, 69.88; H, 6.38; N, 4.94. Found: C, 69.83; H, 6.04; N, 4.87. Example 468 frans. frans-2-f4-Methoxy-3-fluoro p henvn-4-f7-methoxy-1 .3- benzodioxol-5-yl -f2-f N-butyl-N-phenylamino)ethyl1pyrrolidine-3- carboxylic acid Ethyl 2-(4-methoxy-3-fluorophenyl)-4-(7-methoxy- 1 ,3- benzodioxol-5-yl)-1 -[2-(bromoethyl]-pyrrolidine-3-carboxylate, prepared using the procedures of Example 61 A (300 mg), was reacted with N-butyl aniline (190 mg) in 1 mL of dioxane containing 130 mg of diisopropylethylamine to give the ethyl ester. The ester was hydroyzed with sodium hydroxide to give 148 mg of the title compound as a white powder. H NMR (300 MHz, CDCI3) δ 0.90 (t, J=9Hz, 3H), 1.28 (sextet, J=7Hz, 2H), 1.46 (quintet, J=7Hz, 2H), 2.20-2.32 (m, 1 H), 2.68-2.77 (m, 1H), 2.82-2.95 (m, 2H), 3.12-3.22 (m, 2H), 3.30-3.44 (m, 3H), 3.45-3.55 (m, 1 H), 3.62 (d, J=9Hz, 1 H), 3.83 (s, 3H), 3.90 (s, 3H), 5.95 (s, 2H), 6.51 (d, J=7Hz, 2H), 6.55-6.62 (m, 2H), 6.69 (d, J=2Hz, 1 H), 6.84 (t, J=8Hz, 1 H), 7.02-7.15 (m, 3H), 7.19 (dd, J=2Hz, 12Hz, 1 H). Example 469 frans. frans-4-f 1 .4-Benzodioxan-6-yn-2-f4-ethylphenyn-1 -f ff N.N- dibutylaminotoarbonvnmethvnpyrrolidine-3-carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. " Η NMR (300 MHz, CDCI3) δ 0.78 (t, 3H, J=7Hz), 0.88 (t, 3H, J=7Hz), 1.05 (q, 2H, J=7Hz), 1.23 (t, 3H, J=7Hz), 1.28 (m, 2H), 1.45 (m, 2H), 2.64 (q, 2H, J=7Hz), 2.78 (m, 1 H), 2.9-3.2 (envelope, 4H), 3.30 (m, 1 H), 3.40 (m, 3H), 3.60 (m, 1 H), 3.80 (m, 1 H), 4.25 (s, 4H), 6.80 (d, 1 H, J=8Hz), 6.90 (m, 1 H), 6.98 (d, 1 H, J=2Hz), 7.17 (d, 2H, J=8Hz), 7.30 (m, 2H). MS (APCI) m/e 523 (M+H)+. Anal, calc'd for C31 H42N2O5 • 1.1 HOAc: C, 67.73; H, 7.94; N, 4.76. Found: C, 67.81 ; H, 7.55; N, 4.48. Example 470 frans.frans-4-f 1 .4-Benzodioxan-6-yn-2-f4-methoxv p henyn- 1 -ff N- butyl-N-f3-methylPhenylamino carbonvnmethvn p yrrolidine-3- carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CD3OD) δ 0.87 (t, J=7.1 Hz, 3H), 1.30 (m, 2H), 1.44 (m, 2H), 2.30 (s, 3H), 2.80 (d, J=15.2 Hz, 1 H), 2.85 (t, J=9.3 Hz, 1 H), 3.19 (t, J=9.3 Hz, 1 H), 3.33 (d, J=10.2 Hz, 1 H), 3.42-3.61 (m, 3H), 3.79 (s, 3H), 3.91 (d, J=9.8 Hz, 1 H), 4.22 (m, 4H), 6.75-6.86 (m, 6H), 6.95 (d, J=2.0 Hz, 1 H), 7.09 (d, J=8.8 Hz, 2H), 7.22 (d, J=10.2 Hz, 1 H), 7.26 (t, J=7.6 Hz, 1 H). MS (DCI) m/e 559 (M+H+). Anal calcd for C33H38N2O6 • 0.4 CH3CO2C2H5: C, 69.97; H, 6.99; N, 4.72. Found: C, 0.06; H, 6.66; N, 4.48. Example 471 trans. trans-4-( \ .4-Benzodioxan-6-vn-2-f4-methoxyphenvn-1 -ffN- butyl-N-f3-chlorophenylamino)carbonynmethvnpyrrolidine-3- carboxyiic acid Using the procedures described in Example 1 , the title compound was prepared. H NMR (300 MHz, CD3OD) δ 0.87 (t, J=7.0 Hz, 3H), 1.25 (m, 2H), 1.40 (m, 2H), 2.78 (d, J=14.6 Hz, 1 H), 2.86 (t, J=9.0 Hz, 1 H), 3.16 (t, J=9.5 Hz, 1 H), 3.34-3.43 (m, 2H), 3.48-3.62 (m, 3H), 3.79 (s, 3H), 3.85 (d, J=9.5 Hz, 1 H), 4.22 (m, 4H), 6.78 (d, J=8.5 Hz, 1 H), 6.81- 6.86 (m, 3H), 6.93-7.09 (m, 5H), 7.33-7.38 (m, 2H). MS (DCI) m/e 579 (M+H+). Anal calcd for C32H35CIN2O6 ■ 1.1 CH3CO2C2H5 • 0.15 H3PO4: C, 63.30; H, 6.46; N, 4.06. Found: C, 63.54; H, 6.09; N, 3.98. Example 472 frans.frans-4-f 1 .3-Benzodioxol-5-vn-2-f4-methoxyphenvn- 1 - 4- pyridylmethvnpyrrolidine-3-carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CD3OD) δ 2.84 (t, J=9.6 Hz, 1 H), 2.88 (dd, J=9.6, 7.3 Hz, 1H), 3.09 (dd, J=3.3, 9.6 Hz, 1 H), 3.21 (d, J=14.3 Hz, 1 H), 3.53 (m, 1H), 3.78 (s, 3H), 3.81 (m, 2H), 5.92 (m, 2H), 6.73 (d, J=8.1 Hz, 1 H), 6.82 (dd, J=1.8, 8.1 Hz, 1 H), 6.93 (m, 2H), 6.95 (d, J=1.5 Hz, IH), 7.43 (m, 4H), 8.44 (d, J=5.2 Hz, 2H). MS (DCI) m/e 433 (M+H+). Anal caicd for C25H24N2O5 • 0.3 CH3CO2C2H5: C, 68.57; H, 5.80; N, 6.10. Found: C, 68.68; H, 5.60; N, 5.81. Example 473 frans. frans-4-f 1 .3-Benzodioxol-5-vn-2-f4-methoxv p henvn-1 -ff N- b tyl-N-f3-ferf-butylphenvlamino^carbonvnmethvnpyrrolidine-3- carbQxyijp acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CD3OD) δ 0.88 (t, J=7.2 Hz, 3H), 1.23 (s, 9H), 1.26-1.45 (m, 4H), 2.74 (dd, J=15.1 Hz, 1 H), 2.84 (m, 1 H), 3.13 (t, J=9.0 Hz, 1 H), 3.2g (d, J=15.1 Hz, 1 H), 3.50-3.66 (m, 4H), 3.77 (s, 3H), 3.84 (d, J=9.6 Hz, 1 H), 5.92 (s, 2H), 6.74 (d, J=7.7 Hz, 1 H), 6.79- 6.85 (m, 4H), 6.86-6.90 (m, 1 H), 6.99 (t, J=1.8 Hz, 1 H), 7.06 (d, J=1.8 Hz, 1 H), 7.13 (m, 2H), 7.33 (t, J=7.7 Hz, 1 H), 7.42 (m, 1 H). MS (DCI) m/e 587 (M+H+). Anal calcd for C35H42N2O6: C, 71.65; H, 7.22; N, 4.77. Found: C, 71.56; H, 7.33; N, 4.69. Example 474 frans. frans-4-f 1 .3-Benzodioxol-5-yn-2-f4-methoxyphenyn- 1 -ffN- butyl-N-f3-n-butylphenylamino)carbonynmethynpyrrolidine-3- carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CD3OD) δ 0.88 (t, J=7.3 Hz, 3H), 0.92 (t, J=7.3 Hz, 3H), 1.23-1.59 (m, 8H), 2.58 (t, J=7.6 Hz, 2H), 2.75 (d, J=15.3 Hz, 1 H), 2.80 (dd, J=8.5, 9.5 Hz, 1 H), 3.12 (t, J=9.3 Hz, 1 H), 3.29 (d, J=15.6 Hz, 1 H), 3.46 (dd, J=4.9, 9.7 Hz, 1 H), 3.52-3.64 (m, 3H), 3.78 (s, 3H), 3.83 (d, J=9.8 Hz, 1 H), 5.82 (s, 2H), 6.74 (d, J=8.1 Hz, 1H), 6.79- 6.87 (m, 4H), 7.05 (d, J=1.7 Hz, 1H), 7.10 (d, J=8.8 Hz, 2H), 7.20 (d, 7.8H), 7.29 (t, J=7.6 Hz, 1 H). MS (DCI) m/e 587 (M+H+). Anal calcd for C35H42N2O6. C, 71.65; H, 7.22; N, 4.77. Found: C, 71.33; H, 7.28; N, 4.74. Example 475 frflns.frans-4-f3.4-Difluorophenvn-2-f4-ethvlphenvn- 1 -fN-fn-butyn- N-f3-methylphenvnaminocarbonylmethvnpyrrolidine-3-carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (CD3OD, 300 MHz) δ 0.87 (t, 3H, J=7), 1.19 (t, 3H, J=:7), 1.28 (m, 2H), 1.43 (m, 2H), 2.28 (s, 3H), 2.60 (q, 2H, J=7), 2.66 (m, 2H), 3.06 (m, 1 H), 3.21 (d, 1H, J=15), 3.42 (dd, 1 H, J=4,9), 3.58 (m, 3H), 3.71 (d, 1H, J=9), 6.80 (s, 2H), 7.06 (s, 4H), 7.18 (m, 4H), 7.45 (m, 1H). MS (APCI) m/e 535 (M+H)+. Anal calcd for C32H36N2O3F2 • 1.3 HOAc: C, 67.83; H, 6.78; N, 4.57. Found: C, 67.83; H, 6.46; N, 4.70. Example 476 frans. frans-2-f4-Ethylphenvn-4-f 3.4-difluorophen ylY 1 -f N-fn-buty n- N-f3-chloroρhenynaminocarbonylmethvnpyrrolidine-3-carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (CD3OD, 300 MHz) δ 0.82 (t, 3H, J=7), 1.16 (t, 3H, J=7), 1.23 (m, 2H), 1.35 (m, 2H), 2.55 (q, 2H, J=7), 2.66 (m, 2H), 3.01 (t, 1 H, J=9), 3.16 (d, 1 H, J=15), 3.32 (dd, 1H, J=4,9), 3.56 (m, 3H), 3.67 (d, 1 H, J=g), 6.94 (d, 1 H, J=7), 7.02 (m, 5H), 7.14 (m, 2H), 7.32 (m, 3H). MS (APCI) m/e 555 (M+H)+. Anal calcd for C31 H33N2O3CIF2 • 0.6 TFA: C, 61.88; H, 5.42; N, 4.48. Found: C, 61.90; H, 5.62; N, 3.98. Example 477 frans. frans-4-( 1 .4-Benzodioxan-6-yn-2- ( 4-f luorophenvn-1 -f N-butyl- N-f3-chlorophenvnaminocarbonylmethynpyrrolidine-3-carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CD3OD) δ 0.87 (t, J=7 Hz, 3H), 1.10- 1.30 (m, 4H), 2.60-2.75 (m, 2H), 3.03 (t, J=7 Hz, 1 H), 3.15-3.75 (m, 6H), 4.02 (m, 4H), 6.75 (d, J=6 Hz, 1 H), 6.85 (dd, J=7 Hz, 1 H), 6.90 (7.19, J=m Hz, 6H), 7.32-7.43 (m, 3H). MS (DCI) m/e 567 (M+H)+. Anal calcd for C31 H32N2O5FCI ■ 1.6 H2θ: C, 62.49; H, 5.95; N, 4.70. Found: C, 62.20; H, 5.54; N, 4.42. Example 478 frans. frans-4-f Benzof uran-5-vl )-2-f4-ethvlPhenvn-1 -f f f N. N- dibutylaminoϊcarbonvnmethvnpvrrolidine-3-carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CDCI3) δ 0.78 (t, 3H, J=7Hz), 0.84 (t, 3H, J=7Hz), 1.05 (q, 2H, J=7Hz), 1.21 (t, 3H, J=7Hz), 1.25 (m, 2H), 1.45 (m, 2H), 2.62 (q, 2H, J=7Hz), 2.80 (d, 1 H, J=13Hz), 3.0 (m, 2H), 3.15 (m, 2H), 3.35 (m, 1 H), 3.43 (m, 2H), 3.52 (m, 1 H), 4.40 (m, 2H), 6.73 (d, 1H, J=1 Hz), 7.14 (d, 2H, J=8Hz), 7.26 (s, 1 H), 7.31 (d, 2H, J=8Hz), 7.44 (s, 2H), 7.60 (d, 1 H, J=1 Hz), 7.65 (s, 1 H). MS (APCI) m/e 505 (M+H)+. Anal, calc'd for C31 H40N2O4: C, 73.78; H, 7.99; N, 5.55. Found: C, 73.69; H, 7.97; N, 5.21. Example 479 frans. frans-2-f4-Methoxy-3-fluorophenyn-4-f7-methoxy-1 .3- benzodioxol-5-yn- 1 -f2-fN-propyl-N-fpvrrolidine-1 - carbonylmethyl)amino thyl]pyrrotidine-3-carboxylic acid Ethyl 2-(4-methoxy-3-fluorophenyl)-4-(7-methoxy-1 ,3- benzodioxol-5-yl)- 1 -[2-(N-propyl-aminoethyl]-pyrrolidine-3- carboxylate, prepared according to the procedures of Example 61 B (300 mg), N-bromoacetyl pyrrrolidine (132 mg) and diisopropylethylamine (154 mg) were heated for 1 hour at 50 °C in 1 mL of acetonitrile to give the intermediate ethyl ester. The ester was hydrolyzed to the title compound by the method of Example 1 D. 1 H NMR (300 MHz, CDCI3) δ 0.88 (t, J=7Hz, 3H), 1 .30-1.45 (m, 2H), 1.75-1.92 (m, 4H), 2.30-2.40 (m, 1 H), 2.47-2.58 (m, 2H), 2.70-3.00 (m, 5H), 3.24-3.45 (m, 6H), 3.50-3.70 (m, 2H), 3.83 (s, 3H), 3.86 (d, J=9Hz, 1 H), 3.88 (s, 3H), 5.93 (s, 2H), 6.58 (d, J=2Hz, 1H), 6.70 (d, J=2Hz, 1H), 6.87 (t, J=8Hz, 1H), 7.10 (d, J=9Hz, 1 H), 7.21 (dd, J=2Hz, 12Hz, 1 H). Example 480 trans, frans-2-f 4- Methoxyphenvn-4-f 1 .3-benzodioxol-5-yl )- 1 -f2-f fN- fperhydroazepinylcarbonyl DYIeucvnamino ethvnpyrrolidine-3- carboxylic acid Example 480A D-Leucine O-benzyl ester Tosylate salt To benzyl alcohol (8.2 g) dissolved in benzene (30 mL) was added D-leucine (5.0 g) and p-toluenesulfonic acid monohydrate (8.0 g). The reaction was warmed to reflux with removal of water overnight. Once TLC indicated consumption of starting material, the reaction was cooled, and the resulting solid was filtered and washed with EtOAc to give the title compound as a white powder (14.26 g, 99%). Example 480B N-Perhydroazepinylcarbonyl-D-Leucine O-Benzyl ester To the compound resulting from Example 480A (1.0 g) dissolved in chloroform (20 mL) was added triethylamine (0.4 mL). The solution was cooled to 0 °C, and carbonyldiimidazole was added. After 1.5 hours, TLC indicated complete consumption of starting material, so hexamethylene imine (0.327 mL) was added. After 1 hour, an additional amount of hexamethylene imine (0.330 mL) was added, and the reaction was stirred at ambient temperature overnight. The solution was washed with sodium bicarbonate (2 x 20 mL), 1 H3PO4 (2 x 20 mL), and brine (20 mL), dried over Na2Sθ4, decanted and evaporated. The residue was purified by flash chromatography on silica gel eluting with 25 - 50% EtOAc in hexanes to give the title compound as a crystalline solid (0.835 g, 89%). Example 480C N-Perhvdroazepinylcarbonyl-D-Leucine To the compound resulting from Example 480B (200 mg) dissolved in dry ethanol (1.0 mL) was added 10% palladium on carbon (10 mg). After flushing the flask with nitrogen, the reaction was stirred vigorously under an atmosphere of hydrogen for 1 hour. The reaction was filtered through infusorial earth and evaporated to give the title compound (140 mg). Example 480D frans.frans-2-f4-Methoxyphenvn-4-f 1 .3-benzodioxol-5-yn-1 - fcyanomethvn-pyrrolidine-3-carboxylic acid ethyl ester To the compound resulting from Example 1C (510 mg of a 50 % wt. solution in toluene) dissolved in acetonitrile (2.0 mL) was added diisopropylethylamine (0.24 mL), followed by bromoacetonitrile (0.072 mL). After 2 hours, TLC indicated complete comsumption of starting material. The solvent was evaporated, and the residue was purified by flash chromatography on silica gel eluting with 20 - 40% EtOAc in hexanes to give the title compound as a colorless oil (0.28 g, 99%). Example 48QE frans.frans-2-f4-Methoxvphenvn-4-f 1 .3-benzodioxol-5-vn-1 -f2- aminoethyl »-pyrrolidine-3-carboxylic acid ethyl ester To the compound resulting from Example 480D (275 mg) dissolved in 10 mL each of triethylamine and ethanol was added Raney nickel catalyst (0.2 g), and the reaction was placed under a hydrogen atmosphere (4 atmospheres) for 3 days. The reaction was filtered and evaporated. The residue was dissolved in methylene chloride (10 mL) and extracted with 1 M HCl (5 x 1 mL). The combined aqueous extracts were basified and then extracted with methylene chloride (5 x 2 mL). The combined organic extracts were dried with MgSθ4, filtered and evaporated to give the title compound as an unstable oil (0.14 g). Example 480F frans. frans-2-f 4- Methoxyphenvn-4-f 1 .3-benzodioxol-5-yn- 1 -f2-ff N- fperhydroazepinylcarbonvnieucvnaminoϊethvn-pyrrorιdine-3- carboxylic acid, ethyl ester The compound resulting from Example 480E (0.10 g) was dissolved in methylene chloride (3.0 mL), and the compound resulting from Example 480C (0.07 g) was added. The solution was cooled to 0 °C, and EDCI (0.052 g) was added. After 4 hours, the reaction was evaporated and partitioned between water (1 mL), and EtOAc (10 mL). The orgainc solution was washed with water (1 mL) and brine (1 mL), dried over MgS04, filtered and evaporated. The residue was purified by flash chromatography on silica gel eluting with 50 - 60% EtOAc in hexanes to give the title compound as a colorless oil (0.075 g, 48%). Example 480G frans.frans-2-f4-Methoxvphenyn-4-f 1 .3-benzodioxol-5-vn- 1 -f2-f f N- fperhydroazepinvlcarbonvnieucvnamino^ethvnpvrrolidine-3-carboxylic acid The compound resulting from Example 480F (0.75 g) was dissolved in ethanol (1.0 mL) and 5 M. NaOH (0.050 mL) was added. After o 2 hours, additional 5 M NaOH (0.090 mL) was added. After an additional 3.5 hours, the reaction was evaporated. The residue was dissolved in water (5 mL) and washed with diethyl ether (2 x 2 mL). The aqueous solution was acidified with 1 N. H3PO4 to pH = 3. The solid which precipitated dissolved when the mixture was extracted with 5 chloroform (3 x 3 mL). The chloroform extracts were washed with brine (2 mL), dried with MgSθ4, filtered and evaporated to give the title compound as a tan solid (0.053 g). Purification by HPLC (Vydac mC18) eluting with a 10 - 70% gradient of CH3CN in 0.1 %TFA provided suitable material (0.049 g) after lyophilization of the desired 0 fractions. 1 H NMR (CDCI3, 300 MHz) δ 0.82 (dd, 6.4, 4.4 Hz, 6H), 0.87 (dd, J = 5.7, 5.7 Hz, 6H), 1.04-1.28 (m, 3H), 1.34-1.65 (m, 19H), 2.95 (br m, 2H), 3.15-3.40 (m, 14H), 3.40-3.55 (m, 4H), 3.58-3.68 (m, 2H), 3.70- 3.76 (br m, 2H), 3.80 (s, 3H), 3.81 (s, 3H), 4.15 (br m, 2H), 5.10 (br m, 2H), 5.93 (s, 3H), 5.95 (s, 3H), 6.70-6.97 (m, 13H), 7.43-7.56 (br m, 3H), 5 8.2 (br s, 1 H), 8.5 (br s, 1 H). MS(DCI/NH3) m/e 623 (M+H)+. Anal calcd for C34H46N4O7 ■ 2.00 TFA: C, 53.65; H, 5.69; N, 6.58. Found: C, 53.66; H, 5.66; N, 6.54. Example 481 0 frans. frans-4-f 1 .3-Benzodioxol-5-yn-2-f4-methoxyphen vn-1 -fN . N- dif n-hexynaminocarbonylmethvnpyrrolidine-3-carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CD3OD) δ 0.80-0.95 (m, 6H), 1.0 (m, 2H), 1.07 (1.55, J=m Hz, 14H), 2.70 (d, J=13 Hz, 1 H), 2.85-3.15 (m, 4H), 5 3.20-3.60 (m, 9H), 3.64 (d, J=10 Hz, 1 H), 3.79 (s, 3H), 5.90 (m, 2H), 6.70 (d, 8H), 1 , 6.80-6.93 (m, 3H), 7.05 (2, 1 H), 7.35 (d, J=10 Hz, 2H). Anal calcd for C33H46 2O6 • 1.7 H2O: C, 66.35; H, 8.34; N, 4.69. Found: C, 66.32; H, 8.04; N, 4.52. Example 482 frans. frans-4-f 1 .4-Benzodioxan-6-vn-2-f4-fluorophenvn- 1 -fN-butyl- N-f3-methylphenvnaminocarbonvlmethvnpyrrolidine-3-carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. H NMR (300 MHz, CD3OD) δ 0.87 (t, J=7 Hz, 3H), 1.20- 1.35 (m, 2H), 1.35-1.40 (m, 2H), 2.32 (s, 3H), 2.55-2.70 (m, 2H), 2.97 (t, J=7 Hz, 1 H), 3.22 (d, J=14 Hz, 1 H), 3.25-3.70 (m, 5H), 4.20 (m, 4H), 6.97 (d, J=2 Hz, 1 H), 7.09 (m, 2H), 7.15-7.35 (m, 2H). MS (DCI) m/e 547 (M+H)+. Anal calcd for C32H35N2O5F • 1.2 H2O: C, 67.64; H, 6.63; N, 4.93. Found: C, 67.73; H, 6.37; N, 4.70. Example 483 frans. frans-4-f 1 .3-Benzodioxol-5-vn-2-f4-methoxyphenvn- 1 -fffN- butyl-N-f3-nitrobenzyl )amino carbonvnmethynpyrrolidine-3- carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CDCI3 ) δ (rotamer) 8.14 (2H, m), 8.05 (7.83) (1 H, m), 7.60-7.30 (3H, m), 7.13 (1 H, m), 7.10-6.70 (5H, m), 5.94 (2H, m), 5.43 (5.33) (1 H, d, J=12), 4.75 (1 H, bd, J=15), 4.60-4.20 (2H, m), 4.10 (2H, m), 3.80 (3.76) (3H, s), 3.75-3.40 (3H, m), 3.20-2.80 (2H, m), 1.50 (1 H, m), 1.30 (1 H, m), 1.20-1.00 (2H, m), 0.91 (0.78) (3H, t, J=8). MS (DCI/NH3) m/e 590 (M+H+). Anal calcd for C32H35N3O8 ■ 2.1 TFA: C, 52.44; H, 4.51 ; N, 5.07. Found: C, 52.25; H, 4.83; N, 5.71. Example 484 frans. frans-4-f 1 .2-Dihvdrobenzofuran-5-yn-2-f4-ethylphenvn-1 -fffN- butyl-N-f3.4-dimethoxybenzynamino carbonynmethynpyrrolidine-3- carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H (300MHz, CDCI3 ) δ (rotamer) 7.40 (2H, m), 7.30-7.10 (4H, m), 6.90-6.70 (3H, m), 6.48 (1 H, m), 5.45 (1 H, m), 4.65 (1 H, d, J=15), 4.57 (2H, dt, J=9, 3), 4.40-4.00 (5H, m), 3.87 (3.85) (3H, s), 3.84 (1 H, m), 3.83 (3.78) (3H, s), 3.56 (2H, m), 3.20 (2H, t, J=10), 2.90 (1 H, m), 2.64 (2H, q, J=8), 1.52 (1 H, m), 1.31 (2H, m), 1.22 (3H, dt, J=9, 2), 1.07 (1 H, m), 0.02 (0.78) (3H, t, J=8). MS (DCI/NH3) m/e 601 (M+H+). Anal calcd for C36H44N2O6 ■ 1 -35 TFA: C, 61.59; H, 6.06; N, 3.71. Found: C, 61.69; H, 6.04; N, 3.63. Example 485 frans frans-4-f 1 .3-Benzodioxol-5-vn-2-f4-methoxyphenvn- 1 -f ffN- butyl-N-f4-heptynamino^carbonvnmethvnpyrrolidine-3-carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CD3OD) δ 0.71-1.04 (m, 11H), 1.07- 1.35 (m, 6H), 1.73-1.53 (m, 4H), 2.79-3.25 (m, 5H), 3.35-3.44 (m, 1 H), 3.51-3.68 ( , 3H), 3.78-3.89 (m, 1 H), 3.79 (s, 3H), 5.92 (m, 2H), 6.74 (dd, J=1.7, 8.1 Hz, 1 H), 6.85 (td, J=1.7, 8.1 Hz, 1 H), 6.93 (m, 2H), 7.02 (dd, J=1.7, 9.5 Hz, 1 H), 7.36 (m, 2H). MS (CI.) m/e 553 (M+H+). Anal calcd for C32H44N2O6: C, 69.54; H, 8.02; N, 5.07. Found: C, 69.31 ; H, 7.89; N, 5.06. Example 486 frans. frans-2-f 4-Methylcvclohexyn-4-f 1 .3-benzodioxol-5-yn-1 -f N .N- dibutylaminocarbonylmethvπpyrrolidine-3-carboxylic acid Using the procedures described in Example 1 , the title compound was prepared and isolated as an amorphous solid. " Η NMR (CDCI3, 300 MHz) δ 0.88 (3H, d, J = 7Hz), 0.92 (3H, t, J = 7Hz), 0.96 (3H, t, J = 7Hz), 1.05 (1H, m), 1.22-1.40 (7H, m), 1.45-1.65 (6H, m), 1.67-1.84 (4H, m), 3.17-3.45 (6H, m), 3.70 (1H, brm), 3.82 (1 H, dd, J = 9Hz, 15Hz), 3.86 (1 H, d, J = 15Hz), 5.83 (2H, s), 6.73 (1 H, d, J = 8Hz), 6.78 (1 H, dd, J = 2Hz, 8Hz), 6.88 (1 H, d, J = 2Hz). MS (DCVNH3) m/e 501 (M+H)+. Anal calcd for C29H44N2O5 • 0.25 CF3CO2H : C, 66.96; H, 8.43; N, 5.29. Found: C, 66.79; H, 8.60; N, 4.87. Example 487 frans. frans-2-f2-Propylpentyn-4-f 1 .3-benzodioxol-5-vn- 1 -(N.N- dibutylaminocarbonylmethvnpyrrolidine-3-carboxylic acid Using the procedures described in Example 1 , the title compound was prepared and isolated as an amorphous solid. 1 H NMR (CDCI3, 300 MHz) δ 0.85 (6H, m), 0.92 (3H, t, J = 7Hz), 0.97 (3H, t, J = 7Hz), 1.12- 1.40 (13H, m), 1.42-1.68 (6H, m), 2.90 (1 H, m), 3.14-3.30 (2H, m), 3.33 (4H, m), 3.72 (1 H, brm), 3.90 (1 H, brm), 5.93 (2H, dd, J = 2Hz, 4Hz), 6.73 (1 H, d, J = 8Hz), 6.78 (1H, dd, J = 2Hz, 8Hz), 6.88 (1H, d, J = 2Hz). MS (DCI/NH3) m/e 517 (M+H)+. Anal calcd for C30H48N2O5 • 0.35 CF3CO2H : C, 66.24; H, 8.76; N, 5.03. Found: C, 66.26; H, 8.82; N, 4.98. Example 488 trans.trans-4-( \ .4-Benzodioxan-6-yn-2-f4-fluorophenvn- 1 -f N . N- dibutylaminocarbonylmethvnpyrrolidine-3-carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CD3OD) δ 0.83 (t, J=7 Hz, 3H), 0.89 (t, J=7 Hz, 3H), 0.9.0-1.17 (m, 4H), 1.20-1.65 (m, 5H), 2.77d (13, 1 H), 2.87 (dd, J=8, 2 Hz, 1 H), 2.95-3.60 (m, 7H), 3.71 (d, J=9 Hz, 1 H), 4.21 (s, 4H), 6.72 (d, 1 H), 6.91 (dd, J=8 Hz, 1H), 6.97 (d, J=2 Hz, 1 H), 7.05 (t, J=7 Hz, 2H), 7.40-7.50 (m, 2H). MS (DCI) m/e 513 (M+H)+. Anal calcd for C29H37N205F - 1.2C F3COOH: C, 58.07; H, 5.93; N, 4.31. Found: C, 57.94; H, 5.81 ; N, 4.56. Example 489 frans. frans-2-f3-Methylpentvn-4-f 1 .3-benzodioxol-5-yn- 1 -f N. N- dibutylamino-carbonylmethvnpyrrolidine-3-carboxylic acid Using the procedures described in Example 1 , the title compound was prepared and isolated as an amorphous solid. 1 H NMR (CDCI3, 300 MHz) δ 0.83 (3H, t, J = 7Hz), 0.85 (3H, d, J= 7Hz), 0.91 (3H, t, J = 7Hz), 0.97 (3H, t, J = 7Hz), 1.05-1.22 (2H, m), 1.22-1.41 (7H, m), 1.43-1.68 (5H, m), 1.89 (1 H, m), 2.94 (1 H, t, J = 6Hz), 3.15-3.27 (3H, m), 3.29-3.60 (5H, m), 3.72 (1 H, brd, J = 6Hz), 3.92 (1 H, brd, J = 13.5Hz), 5.93 (2H, dd, J = 2Hz, 4Hz), 6.73 (1 H, d, J = 8Hz), 6.78 (1 H, dd, J = 2Hz, 8Hz), 6.88 (1 H, d, J = 2Hz). MS (DCI/NH3) m/e 489 (M+H)+. Anal calcd for C28H44N2O5 • 0.30 CF3CO2H: C, 65.70; H, 8.54; N, 5.36. Found: C, 65.93; H, 8.81 ; N, 4.84. Example 490 frans. frans-2-(2-Ethylbutyn-4-f 1 .3-benzodioxol-5-vn- 1 -f N. N- dibutylaminocarbonylmethynpyrrolidine-3-carboxylic acid Using the procedures described in Example 1 , the title compound was prepared and isolated as an amorphous solid. 1 H NMR (CDCI3, 300 MHz) δ 0.85 (6H, m), 0.92 (3H, t, J = 7Hz), 0.97 (3H, t, J = 7Hz), 1.13- 1.41 (13H, m), 1.43-1.72 (6H, m), 2.96 (1H, brm), 3.12-3.52 (6H, m), 3.55-3.70 (1 H, m), 3.70-3.86 (2H, m), 3.99 (1 H, brm), 5.93 (2H, dd, J = 2Hz, 4Hz), 6.73 (1 H, d, J = 8Hz), 6.78 (1H, dd, J = 2Hz, 8Hz), 6.88 (1H, d, J = 2Hz). MS (DCI/NH3) m/e 489 (M+H)+. Anal calcd for C-28H44N2O5 • 0.45 CF3CO2H: C, 64.28; H, 8.30; N, 5.19. Found: C, 64.16; H, 8.38; N, 5.08. Example 491 frans. frans-2-(3-Fluoro-4-methoxyphenvn-4-f 1 .3-benzodioxol-5-y 11- 1 -f2-f N-isobutyl-N-fbutanesulfonylamino))ethvnpyrrolidine-3- carboxylic acid Using the procedures described in Example 66, the title compound was prepared. 1 H NMR (CD3OD, 300 MHz) δ 0.74 (d, 3H, J=7), 0.83 (d, 3H, J=7), 0.94 (t, 3H, J=7), 1.44 (hex, 2H), 1.67 (m, 4H), 2.91 (d, 2H, J=8), 3.04 (dd, 2H, J=8,10), 3.1-3.6 (m, 5H), 3.78 (m, 2H), 3.92 (s, 3H), 4.60 (m, 1H), 5.97 (s, 2H), 6.82 (d, 1 H, J=8), 6.89 (dd, 1 H, J=2, 8), 7.01 (d, 1 H, J=2), 7.22 (t, 1 H, J=9), 7.39 (m, 2H). MS (ESI) m/e 579 (M+H)+. Example 492 frans. frans-2-f4-Methoxy-3-fluorophenvn-4-f 1 .3-benzodioxol-5-vn- 1 -f2-fN-propyl-N-[4-ethylpyrimidin-2-yllamino)ethvπpyrrolidine-3- carboxylic acid 1-Dimethylamino-1 -pentene-3-one, prepared by the method described in Syn. Comm. 12 (1 ), 35 (1982), was converted to 2-amino- 4-ethylpyrimidine with guanidine by the method of Chem. Ber. 97, 3397 (1964). This material was converted to 2-bromo-4-ethyl-pyrimidine with NaNθ2 and HBr, using the method of Helv. Chim. Acta 75, 1629 (1992). This bromopyrimidine was reacted with ethyl 2-(4- methoxphenyl)-4-(1 ,3-benzodioxol-5-yl)-1 -[2-(N-propylamino)propyl]- pyrroIidine-3-carboxylate, prepared using the procedures of Example 61 B, using the procedure for Example 418, to give the title compound as a white powder. 1 H NMR (300 MHz, CDCI3) δ 0.83 (t, J=7Hz, 3H), 1.11 (t, J=7Hz, 3H), 1.45 (sextet, J=7Hz, 2H), 2.18-2.27 (m, 1 H), 2.45 (q, J=7Hz, 2H), 2.80-2.97 (m, 3H), 3.40-3.75 (m, 7H), 3.83 (s, 3H), 5.85 (s, 2H), 6.25 (d, J=4Hz, 1H), 6.68 (d, J=8Hz, 1 H), 6.79 (dd, J=2Hz, 8Hz, 1H), 6.82 (t, J=9Hz, 1 H), 6.92 (d, J=2Hz, 1 H), 7.05 (d, J=9Hz, 1 H), 7.15 (dd, J=2Hz, 12Hz, 1 H), 8.10 (d, J=4Hz, 1 H). Example 493 trans. trans-4-( \ .3-Benzodioxol-5-vn-2-f4-methoxyphenvn-1 -ff N- butyl-N-f3.4-dimethylphenynaminocarbonyl1 methyl) pyrrol idine-3- carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. H NMR (300 MHz, CD3OD) δ 0.87 (t, J=7.3 Hz, 3H), 1.23- 1.36 (m, 2H), 1.38-1.43 (m, 2H), 2.22 (s, 3H), 2.29 (s, 3H), 2.79 (d, J=14.9 Hz, 1 H), 2.84 (dd, J=8.6, 9.7 Hz, 1H), 3.16 (t, J=9.5 Hz, 1 H), 3.32 (d, J=15.3 Hz, 1 H), 3.43-3.61 (m, 4H), 3.79 (s, 3H), 3.88 (d, J=9.8 Hz, 1H), 5.93 (s, 2H), 6.74 (m, 3H), 6.83 (m, 3H), 7.04 (d, J=1.7 Hz, 1 H), 7.11 (m, 3H). MS (CI.) m/e 559(MH+). Anal calcd for C33H38N2O6O.3H2O: C, 70.27; H, 6.90; N, 4.97. Found: C, 70.24; H, 6.62; N, 4.58. Example 494 frans. frans-2-f 3- ethyl pent-3-en- 1 -yn-4-f 1 ,3-benzodioxol-5-yn- 1 - f N .N-dibutylaminocarbonylmethvnpyrrolidine-3-carboxylic acid Using the procedure described in Example 1 , the title compound was prepared and isolated as an amorphous solid. 1 H NMR (CDCI3, 300 MHz) δ 0.92 (3H, t, J = 7Hz), 0.97 (3H, t, J = 7Hz), 1.22-1.40 (5H, m), 1.44-1.61 (8H, m), 1.82 (1 H, brm), 2.02 (2H, m), 3.05-3.30 (4H, m), 3.3.8 (1H, m), 3.55 (1 H, brm), 3.85 (2H, m), 4.12 (1 H, brd, J = 15Hz), 5.11 (1 H, dd, J = 6Hz, 12Hz), 5.93 (2H, s), 6.73 (1 H, d, J = 8Hz), 6.78 (1 H, dd, J = 2Hz, 8Hz), 6.88 (1 H, d, J = 2Hz). MS (DCI/NH3) m/e 487 (M+H)+. Anal calcd for C28H42N2O5 • 0.7 CF3CO2H : C, 62.34; H, 7.60; N, 4.95. Found: C, 62.49; H, 7.43; N, 4.73. Example 495 1 -f N-Phenylaminocarbonylmethyn-2-f4-methoxy p henvn-4-f 1 .3- benzodioxol-5-ynpyrrolidine-3-carboxylic acid Example 495A N-Phenylbromoacetamide To a stirred solution of aniline (7.40 mmol) in methylene chloride (25 mL) at -50 °C was added successively N,N-diisopropylethylamine (1.58 mL, 8.14 mmol, 1.1 eq) and bromoacetyl bromide (0.72 mL, 7.40 mmol, 1 eq) such that the temperature did not exceed -40 °C On completion of the addition, the cooling bath was removed, and the reaction mixture was allowed to warm to room temperature. After stirring for a further 30 minutes, the mixture was diluted with ether (70 mL) and poured into 1 N. sodium bisulfate solution. The phases were separated, and the upper layer was washed successively with water and brine. The organic phase was dried (Na2S04) and the solvent evaporated to half volume, at which point the product crystallized. The crystals were removed by vacuum filtration to afford the title compound. Example 495B frans . frans- 1 -f N-Phenylaminocarbonylmethyn-2-f4-methoxyphenvn- 4-f 1 .3-benzodioxol-5-ynpyrrolidine-3-carboxylic acid Using the procedures described in Example 1 and the compound resulting from Exampe 495A, the title compound was prepared. H NMR (300 MHz, CDCI3) δ 8.8 (bs, 1 H) 7.49 (2H, d, J=8Hz), 7.38 (4H, m), 7.11 (1 H, tt, J=8&2Hz), 6.99 (1 H, d, J=2Hz), 6.91 (2H, d, =8Hz), 6.86 (1 H, d, J=2Hz), 6.81 (1 H, d, J=8Hz), 5.99 (1 H, d, J=2Hz), 5.98 (1 H, d, J=2Hz), 3.94 (1 H, d, J=10Hz), 3.78 (3H, s), 3.70 (1 H, ddd, J=6, 5&3Hz), 3.42 (1 H, dd, J=10&3Hz), 3.41 (1H, d, J=16Hz), 3.18 (1H, dd, J=11&9Hz), 3.01 (1 H, t, J=10Hz), 2.93 (1 H, d, J=16Hz). MS (DCI, NH3) m/e 475 (M+H+). Anal. Calc for C-27H26N2O6 • H2O: C, 65.85, H, 5.73, N 5.69, Found: C, 65.95, H, 5.52, N, 5.38. Example 496 frans. frans- 1-fN-f 2.3-Dimethylphenvnaminocarbonylmethvn-2-f 4- methoxyphenvn-4-f1.3-benzodioxol-5-vnpyrrolidine-3-carboxylic acid Using the procedures described in Example 1, the title compound was prepared. 1 H NMR (300 MHz, CDCI3) δ 8.68 (1H, bs), 7.64 (d, J=8Hz), 7.38, (2H, d, J=8Hz), 7.09 (1H, t, =8Hz), 6.97, (1H, d, J=8Hz), 6.90 (1H, d, J=2Hz), 6.88 (2H, d, J=8Hz), 6.82 (1H, dd, J=8&3Hz), 6.76 (1H, d, J=8Hz), 5.97 (1H, d, =2Hz), 5.96 (1H, d, J=2Hz), 3.95 (1H, d, J=10Hz), 3.80 (3H, s), 3.70 (1H, ddd, J=6, 5&3Hz), 3.48 (1H, dd, J=10&3Hz), 3.44 (1H, d, J=16Hz), 3.18 (1H, dd, J=11&9Hz), 3.06 (1H, t, =10Hz), 2.96 (1H, d, =16Hz), 2.31 (3H, s), 2.16 (3H, s). MS (DCI, NH3) m/e 503 (M+H+). Anal. Calc for C29H30N2O6 ■ 0.5 H2O: C, 68.09, H, 6.11, N, 5.48. Found: C, 68.13, H, 5.91, N, 5.29. Example 497 frans. frans- 1-fN-f 2.4-Dimethylphenvnaminocarbonylmethvn-2-f 4- methoxyphenvn-4-f1.3-benzodioxol-5-ynpyrrolidine-3-carboxylic acid Using the procedures described in Example 1, the title compound was prepared. 1 H NMR (300 MHz, CDCI3) δ 8.60 (1H, bs), 7.78 (d, J=8Hz), 7.38, (2H, d, =8Hz), 6.99 (1H, m), 6.95, (1H, d, J=8Hz), 6.94 (1H, d, =2Hz), 6.88 (2H, d, =8Hz), 6.82 (1H, dd, J=8&3Hz), 6.77 (1H, d, J=8Hz), 5.97 (1H, d, J=2Hz), 5.96 (1H, d, =2Hz), 3.92 (1H, d, J=10Hz), 3.79 (3H, s), 3.68 (1H, ddd, J=6, 5&3Hz), 3.43 (1H, dd, J=10&3Hz), 3.42 (1H, d, J=16Hz), 3.18 (1H, dd, =11&9Hz), 3.04 (1H, t, J=10Hz), 2.95 (1H, d, J=16Hz), 2.29 (3H, s), 2.24 (3H, s). MS (DCI, NH3) m/e 503 (M+H+). Anal. Calc for C29H30N2O6 ■ 0.75 H2O: C, 67.50, H, 6.15, N 5.43. Found: C, 67.42; H, 5.95; N, 5.13. Example 498 frans. frans- 1-fN-f 2.5-Dimethylphenvnaminocarbonylmethvn-2-f 4- methoxyphenvn-4-f1.3-benzodioxol-5-vnpyrrolidine-3-carboxylic acjd . Using the procedures described in Example 1, the title compound was prepared. " Η NMR (300 MHz, CDCI3) δ 8.62 (1H, bs), 7.79 (1H, bs), 7.38, (2H, d, J=8Hz), 7.03 (1H, d, J=8Hz), 6.95, (1H, d, J=8Hz), 6.94 (1H, d, =2Hz), 6.88 (2H, d, J=8Hz), 6.82 (1H, dd, J=8&3Hz), 6.77 (1H, d, J=8Hz), 5.97 (2H, s), 3.92 (1H, d, J=10Hz), 3.78 (3H, s), 3.70 (1H, ddd, J=6, 5&3Hz), 3.48 (1H, dd, J=10&3Hz), 3.42 (1H, d, =16Hz), 3.18 (1H, dd, J=11&9Hz), 3.04 (1H, t, J=10Hz), 2.95 (1H, d, =16Hz), 2.29 (3H, s), 2.24 (3H, s). MS (DCI, NH3) me 503 (M+H+). Anal. Calc for C29H30N2O6 • 0.5 H2O: C, 68.09; H, 6.11; N, 5.48. Found: C, 67.72; H, 5.89; N, 5.25. Example 499 frans.frans-1-fN-f3.4-Dimethvlphenvnaminocarbonylmethvn-2-f4- methoxyDhenyn-4-f1.3-benzodioxol-5-vnpyrrolidine-3-carboxylic acid Using the procedures described in Example 1 , the title compound was prepared. 1 H NMR (300 MHz, CDCI3) δ 8.73 (1H, bs), 7.38 (2H, bd, J=8Hz), 7.30, (1H, d, J=3Hz), 7.20 (1H, bs), 7.08, (1H, d, J=8Hz), 7.01 (1H, bs), 6.90 (2H, d, J=8Hz), 6.85 (1H, bs), 6.80 (1H, d, =8Hz), 5.99 (1H, d, J=3Hz), 5.98 (1H, d, J=3Hz), 3.92 (1H, d, =10Hz), 3.78 (3H, s), 3.70 (1H, ddd, J=6, 5&3Hz), 3.48 (1H, dd, =10&3Hz), 3.42 (1H, d, J=16Hz), 3.18 (1H, dd, J=11&9Hz), 3.04 (1H, t, J=10Hz), 2.95 (1H, d, J=16Hz), 2.25 (3H, s), 2.21 (3H, s). MS (DC!, NH3) m/e 503 (M+H+). Anal. Calc for C29H30N2O6 ■ 0.75 H2O: C, 67.50; H, 6.15; N 5.43. Found: C, 67.24; H, 5.94; N, 5.20. Example 500 frans. frans- 1-fN-f 3.5-Dimethylphenvnaminocarbonylmethvn-2-f 4- methoxyphenvn-4-f1.3-benzodioxol-5-ynpy rroli dine-3-carboxylic acid Using the procedures described in Example 1, the title compound was prepared. 1 H NMR (300 MHz, CDCI3) δ 8.75 (1H, bs), 7.35, (2H, d, J=8Hz), 7.10 (2H, s), 7.02 (1H, d, J=3Hz), 6.90 (2H, d, =8Hz), 6.84 (1H, d, J=2Hz), 6.80, (1H, d, =8Hz), 6.76 (1H, bs), 5.99 (1H, d, J=3Hz), 5.98 (1H, d, J=3Hz), 3.92 (1H, d, J=10Hz), 3.79 (3H, s), 3.68 (1H, ddd, J=6, 5&3Hz), 3.40 (2H, m), 3.18 (1H, dd, J=11&9Hz), 2.98 (1H, t, J=10Hz), 2.88 (1H, d, J=16Hz), 2.3 (6H, s). MS (DCI, NH3) m/e 503 (M+H+). Anal. Calc for C-29H30N2O6 • 0.5 H2O: C, 68.09; H, 6.11; N 5.48. Found: C, 67.93; H, 6.01; N, 5.19. Example 5Q1 Alternate Preparation of (+\-trans. trans- 1 -fN. N-Di-n-butylaminocarbonylmethvn-2-f 4- methoxyphenyn-4-f 1 .3-benzodioxol-5-vn p yrrolidine-3-carhoxylic acid Hydrochloride Salt Example 501 A N. N-Dibutvl bromoacetamide To a solution of bromoacetyl bromide (72.3 mL, 830 mmol) in o toluene (500 mL) cooled to 0 °C was added a solution of dibutylamine (280.0 mL, 1.66 mol) in toluene (220 mL) via an addition funnel maintaining the reaction temperature below 10 °C Upon completion of the addition, the reaction mixture was stirred at 0 °C for 15 minutes. A solution of 2.5% aqueous H3PO4 (500 mL) was slowly introduced, and 5 the reaction mixture was allowed to warm to room temperature with vigorous stirring. The solution is 2.5% phosphoric acid by weight. The layers were separated and the organic phase washed with water (500 mL) and concentrated to provide the bromoacetamide as a solution in toluene. 0 Example 501 B 5-f2-Nitrovinyn-1 .3-benzodioxole To piperonal (15.55 kg, 103.5 mol) under mechanical stirring and under nitrogen was added ammonium acetate (13.4 kg, 173.8 mol), 5 acetic acid (45.2 kg), and nitromethane (18.4 kg, 301.4 mol) sequentially. The mixture was warmed to 70 °C After about 30 minutes, the yellow product began to crystallize. The reaction temperature was raised to 80 °C and stirred for about 10 hours until minimal piperonal remains. The somewhat thick reaction mixture was 0 cooled to 10 °C and filtered. The precipitate was washed with acetic acid (2 x 8 kg) and then water (2 x 90 kg). The product was dried under a nitrogen purge and then in a vacuum oven at 50 °C for 2 days to afford 15.94 kg (80%) of the title compound as a bright yellow solid. Example 501 C 4-Methoxybenzoyl acetate To potassium t-amylate (25 wt %, 50.8 kg, 99.26 mol) in toluene (15.2 kg) cooled to 5 °C under mechanical stirring and under nitrogen was added a mixture of 4-methoxyacetophenone (6.755 kg, 44.98 mol) and diethyl carbonate (6.40 kg, 54.18 mol) in toluene over 1 hour maintaining the temperature below 10 °C The reaction mixture was heated to 60 °C for 8 hours until no 4-methoxyacetophenone was detected by HPLC. The mixture was cooled to 20 °C and quenched by adding to a mixture of acetic acid (8 kg) and water (90 kg) over 30 minutes while maintaining the temperature at <20 °C The layers were separated, and the organic layer was washed with 5% sodium bicarbonate solution (41 kg) and concentrated to 14.65 kg. The temperature is maintained below 50 °C during the distillation. The yellow product concentrate was assayed by HPLC against an external standard and the yield was found to be 9.40 kg (94%). Example 501 D Ethyl 2-f4-methoxybenzoyn-4-nitromethyl-3-f 1 ,3-benzodioxol-5-yn butyrate To the compound resulting from Example 501 B (7.5 kg, 37.9 mol) suspended in THF (56 kg) with mechanical stirring under nitrogen was added the compound resulting from Example C (8.4 kg, 37.9 mol). The mixture was cooled to 17 °C, sodium ethoxide (6.4 g, 0.095 mol) was added, and the reaction was stirred for 30 minutes. After about 15 minutes, the nitrostyrene was completely dissolved. Soc i ethoxide (6.4 g, 0.095 mol) was added, and the mixture was stirred at 25 °C until HPLC shows less than 1 area % ketoester remaining. The reaction was concentrated to 32.2 kg which was determined by HPLC assay to be -14.9 kg (95%). Example 501 E Ethyl cis. c/s-2-f4-methoxyphenvn-4-f 1 .3-benzodioxol-5-vn pyrrolidine-3-carboxylate Raney nickel (20.0 g), from which the water had been decanted, was charged to a stirred hydrogenator equipped with a thermocouple. THF (20 mL), the crude compound resulting from Example 501 D (40.82 g, 0.0482 mol), and acetic acid (2.75 mL, 0.0482 mol) were added sequentially. The mixture was put under a hydrogen atmosphere at 60 psi until the hydrogen uptake slowed dramatically. TFA was added, and the mixture was hydrogenated at 200 psi until HPLC shows no residual imine and <2 area % nitrone. The catalyst was filtered away and washed with 100 mL of methanol. The filtrate was assayed by HPLC and found to contain 13.3 g (75% yield) of the cis, cis-pyrrolidine compound. The filtrate was concentrated and chased with additional THF (200 mL) to give a final volume of 100 mL. The mixture was neutralized with 2 N. NaOH solution (50 mL), diluted with water (200 mL), and extracted with ethyl acetate (2 x 100 mL). The combined nearly colorless ethyl acetate layers were assayed against an external standard by HPLC to be13.0 g (73%) of the title compound. Example 501 F Ethyl trans. frans-2-f4-methoχyphenvn-4-f 1 .3-benzodioxol-5-yn pyrrolidine-3-carboxylate The solution of the compound resulting from Example 501 E (38.1 g, 0.103 mol) was chased with ethanol (200 mL) to a final volume of 100 mL and sodium ethoxide (3.40 g, 0.050 mol) was added. The mixture was heated to 75 °C When HPLC shows <3% of the cis.cis isomer remaining, the mixture was cooled to room temperature. The product was assayed by HPLC against an external standard and found to contain 34.4 g (90% yield) of the title compound. The crude compound solution was concentrated and the residue taken up in isopropyl acetate (400 mL). The organic layer was washed with water (2 x 150 mL) and then extracted with 0.25 M. phosphoric acid solution (2 x 400 mL). The combined phosphate layers were stirred with ethyl acetate (200 mL) and neutralized to pH 7 with solid sodium bicarbonate (21 g). The organic layer was separated and found to contain 32.9 g (87%) of the title compound. Example 501 G Ethyl f2R.3R. 4S + -2-f4-methoxyphenvn-4-f1 .3-benzodioxol-5-yn pyrrolidine-3-carboxylate. fSW+1 mandelate salt The solution resulting from Example 501 F was chased with acetonitrile (100 mL) to give a final volume of 50 mL. (S)-(+)-Mandelic acid (2.06 g, 0.0136 mmol) was added and allowed to dissolve. The mixture was seeded with the product and allowed to stir at room temperature for 16 hours. The reaction mixture was cooled to 0 °C and stirred for 5 hours. The product was filtered and dried in a vacuum oven with a nitrogen purge for 1 day at 50 °C to give 5.65 g (40%) of the title compound. The purity of the product can be determined by chiral HPLC using Chiralpak AS, isocratic elution with 95:5:0.05 hexane-ethanol-diethylamine; flow - 1 mlJmin.; UV detection at 227 nm. Retention times: (+)-enantiomer: 15.5 min.; (-)-enantiomer: 21.0 min. Example 501 H f2R.3R.4SYf+ϊ-2-f4-methoxyphenyl)-4-f 1 .3-benzodioxol-5-vn-1 -fN.N- dibutylaminocarbonylmethyh- pyrrolidine-3-carboxylic acid The compound resulting from Example 501 G (20.0 g, 0.0383 mol) was suspended in ethyl acetate (150 mL) and 5% sodium bicarbonate solution (150 mL). The mixture was stirred at room temperature until the salt dissolved and carbon dioxide evolution had ceased. The organic layer was separated and concentrated. The residue was chased with acetonitrile (200 mL) to a final volune of 100 mL and cooled to 10 °C Diisopropylethylamine (11.8 mL, 0.0574 mol) and the compound resulting from Example A (10.5 g, 0.0421 mol) were added, and the mixture was stirred for 12 hours at room temperature. The reaction mixture was concentrated and chased with ethanol (200 mL) to a final volume of 100 mL. Sodium hydroxide solution (40%, 20 mL, 0.200 mol) was added, and the mixture was heated at 60 °C for 4 hours until HPLC showed no starting material remaining. The reaction mixture was poured into water (400 mL) and washed with hexanes (2 x 50 mL). The aqueous layer was washed with hexane (2 x 20 mL). A stirred mixture of the aqueous layer and ethyl acetate (400 mL) was neutralized to pH 5 with concentrated HCl (12 mL). The organic layer was separated and found to contain 18.3 g (94% yield) of the title compound. Example 5011 f2R.3R.4SW+V2-f4-methoxyphenyl)-4-f 1.3-benzodioxol-5-vn-1 -fN.N- dibutylaminocarbonylmethvn- pyrrolidine-3-carboxylic acid hydrochloride salt To a solution of the compound of Example 501 H in ethyl acetate at room temperature in a mechanically stirred vessel equipped with a thermocouple, was added 39.4 mL of 1 N HCl in ethanol (0.0394 mol) The resultant solution was filtered to remove foreign matter, concentrated in vacuo, and chased with ethyl acetate (400 mL). The solution was seeded repeatedly, as the solvent was removed, until crystallization was initiated. The mixture was concentrated to a volume of 100 mL, and the product was filtered and washed with ethyl acetate (25 mL). The resultant white solid was dried in a vacuum oven under a nitrogen purge at 50 °C to afford 17.6 g (90%) of the title compound. Example 502 trans. frans-2-f2-Methylpentvn-4-f 1 .3-benzodioxol-5-vn-1 -f N.N- dibutylaminocarbonylmethvπ-pyrrolidine-3-carboxylic acid Example 502A f± Ethyl 3-methylhexanoate To a slurry of 60% sodium hydride (2.26g, 57 mmol) in 10mL of hexanes and 100mL of diethyl ether was added triethylphosphonoacetate (10.3mL, 52mmol). Once gas evolution ceased, 2-pentanone (6.0mL, 64mmoi) was added. After 3 hours at room temperature, the reaction was quenched with water, and partitioned into ether. The organic layer was washed with water and brine, dried with anhydrous sodium sulfate, filtered, and the solvent was removed under reduced pressure. The residue was dissolved in 50mL of ethanol and 10% palladium on carbon (6.0g) was added. The vessel was pressurized to 4 atmosphere of hydrogen, and was shaken at room temperature for 3 hours. The reaction was filtered and the solvent was removed under reduced pressure to give 3.0g of the title compound. Example 502B f±VEthyl 5-methyl-3-oxooctanoate To a solution of ethyl 3-methylhexanoate in 150mL of ethanol was added sodium hydroxide (2.3g, 57.6mmol). After 48 hours at room temperature, solvent was removed under reduced pressure, and the residue was dissolved in 150mL of water. The solution was washed with ether, then acidified with concentrated hydrochloric acid and washed with methylene chloride. The organic layer was dried with anhydrous magnesium sulfate, filtered, and the solvent was removed under reduced pressure to give 2.7g of the corresponding acid from which 3.9g of the title compound was prepared by the method of Bram and Vilkas, Bui. Chem. Soc. Fr., g45 (1964). Example 502C trans. frans-2-f2-Methylpentyn-4-f 1 .3-benzodioxol-5-yn-1 -fN.N- dibutylaminocarbonylmethvn-pyrrolidine-3-carboxylic acid Using the procedures described in Example 1 and substituting ethyl 5-methyl-3-oxooctanoate for ethyl (4-methoxybenzoyl)acetate afforded the title compound, which was isolated by lyophilization from dilute aqueous TFA/CH3CN. Note that the multiplicity of the signals in the aryl region of the NMR spectrum reflects a 1 :1 mixture of diastereomers on the alkyl chain. 1 H NMR (CDCI3, 300 MHz) δ 0.8-1.0 (m, 12H), 1.2-1.4 (m, 7H), 1.45-1.6 (m, 6H), 1.6-1.74 (m, 1 H), 1.8-2.0 (m, 1 H), 3.1-3.4 (m, 5H), 3.67-3.78 (m, 1 H), 3.8-3.91 (m, 1 H), 4.0-4.2 (m, 2H), 4.3-4.5 (m, 2H), 5.93 (d, J=1.5 Hz, 2H), 6.73 (dd, J=8.1 , 1.2 Hz, 1H), 6.79 (ddd, J=7.8, 1.8, 1.8 Hz, 1 H), 6.86 (dd, J=3.9, 1.5 Hz, 1H). MS (DCI/NH3) m/e 489 (M+H) + . Anal calcd for C28H44N2θ5*1.0 TFA- 0.5 H2O: C, 58.91 ; H, 7.58; N, 4.58. Found: C, 58.91 ; H, 7.58; N, 4.45. Example 503 trans. frans-2-f2.2-Dimethylpentvn-4-f 1 .3-benzodioxol-5-vn- 1 -f N .N- dibutylaminocarbonylmethvn-pyrrolidine-3-carhoxylic acid Ethyl 3,3-dimethylhexanoate was prepared using the general procedure of Cahiez et al., Tetrahedron Lett., 3J_, 7425 (1990). Using the procedures described in Example 502 and substituting ethyl 3,3- dimethylhexanoate for ethyl 3-methylhexanoate afforded the title compound, which was isolated by lyophilization from dilute aqueous o TFA/CH3CN. 1 H NMR (CDCI3, 300 MHz) δ 0.80-0.99 (m, 15H), 1.10-1.37 (m, 8H), 1.43-1.58 (m, 4H), 1.77-1 .97 (m, 2H), 3.48-3.12 (m, 5H), 3.60- 3.69 (m, 1 H), 3.75-3.86 (m, 1 H), 3.95-4.16 (m, 2H), 4.28-4.4 (m, 2H), 5.94 (s, 2H), 6.74 (d, J=7.8 Hz, 1 H), 6.8 (dd, J=8.1 , 1.5 Hz, 1 H), 6.87 (d, J=1.8 Hz, 1 H). MS (DCI/NH3) m/e 503 (M+H) + . Anal calcd for 5 C29H46N2O5-1.05 TFA: C, 60.01 ; H, 7.62; N, 4.50. Found: C, 60.21 ; H, 7.37; N, 4.33. Example 504 trans. frans-2-f2-f 1 .3-Dioxo-2-ynethyn-4-f 1 .3-benzodioxol-5-yn- 1 - 0 fN.N-dibutylaminocarbonylmethvn-pyrrolidine-3-carboxylic acid Example 504A Ethyl 5-f 1 .3-dioxolvn-3-oxopentanoate 5 The title compound was synthesized from ethyl acetoacetate and 2-bromomethyl-1 ,3-dioxane, according to the procedure of Huckin and Weiler, Tetrahedron Lett. 3927, (1971). Sodium hydride 4.97 g (0.124 mol), as a 60% mineral oil dispersion, was weighed into a 250 mL flask, into which 80 ml of 0 tetrahydrofuran was directly added. The flask was capped with septum cap, flushed with nitrogen, and cooled in an ice bath. To above stirred slurry was added dropwise 15.0 mL (0.1 18 mol) ethyl acetoacetate. After the addition was complete, the resulting mixture was stirred at 0 °C for additional 10 min. To above mixture was then added 48.4 mL 5 (0.121 mol) n-butyl lithium, a 2.50 M solution in hexane, in a dropwise manner. The resulting orange color solution was stirred for 10 min before 13.5 mL (0.130 mol) bromomethyl-1 ,3-dioxane was added in one portion. The reaction mixture was then allowed to warm to room temperature and stirred for additional 120 min before it was then quenched by slow addition of 9.8 ml (ca. 0.12 mol) concentrated hydrochloric acid. The biphasic mixture was poured to 50 ml of water and extracted with 150 ml of ethyl ether. The aqueous layer was extracted thoroughly with additional ethyl ether. The ethereal extracts were combined, washed with 2x50 ml of saturated brine, dried over anhydrous magnesium sulfate, filtered and evaporated under reduced o pressure to give an brown oily residue. The crude product was purified using silica gel flash chromatography eluting with 20% ether/hexane to give 5.40 g (20%) of b-keto ester as a light yellow oil. Example 504C 5 trans, frans-2-f 2-f 1 .3-Dioxo-2-vnethvn-4- 1 .3-benzodioxol-5-vn-1 - fN.N-dibutylaminocarbonylmethvn-pyrrolidine-3-carboxylic acid Using the procedures described in Example 502 and substituting ethyl 5-(1 ,3-dioxolyl)-2-oxopentanoate for ethyl 3-methylhexanoate 0 afforded the title compound. H NMR (CDCI3, 300 MHz) 6 0.93 (t, J = 7.2 Hz, 3H), 0.95 (t, J = 7.2 Hz, 3H), 1.23-1.38 (m, 4H), 1.52 (sextet, J = 7.9 Hz, 4H), 1.85-1.95 (m, 2H), 2.02-2.17 (m, 2H), 3.18 (dd, J = 6.0 Hz, 9.0 Hz, 2H), 3.30 (dd, J = 9.0 Hz, 18.0 Hz, 2H), 3.35 (m, 1H), 3.79 (dd, J = 3.6 Hz, 6.9 Hz, 1 H), 3.83-3.88 (m, 3H), 3.97 (dd, J = 4.8 Hz, 6.0 Hz, 1 H), 4.05 5 (q, J = 9.6 Hz, 2H), 4.30-4.40 (m, 1 H), 4.37 (s, 2H), 4.87 (t, J = 3.6 Hz, 1H), 5.94 (s, 2H), 6.73 (d, J = 8.1 Hz, 1H), 6.79 (dd, J = 1.8 Hz, 8.1 Hz, 1 H), 6.87 (d, J = 1.8 Hz, 1 H). MS (APCI) (M+H)+ at m/e 505. Anal calcd for C27H40N2O7-1.2 TFA: C, 55.05; H, 6.47; N, 4.37. Found: C, 55.12; H, 6.44; N, 4.27. 0 Example 505 5-ylY1 -fN . N-dibutyl aminocarbonyl methyn-pyrrolidine-3-carboxy lie add Example 505A Ethvl 5-f2-tetrahvdro-2H-pyran)-3-oxopentanoate Using the procedure of Huckin and Weiler, Tetrahedron Lett. 3027, (1971), the title compound was prepared from ethyl acetoacetate and 2-(bromomethyl)tetrahydro-2H-pyran as a light yellow oil. Example 5Q5B trans. trans-2-(2-( 2-Tetrahvdro-2H-pyran)ethvn-4-f 1 .3-benzodioxol- o 5-ylV 1 -fN . N-dibutylaminocarbonylmethyn-pyrrolidine-3-carboxylic acid Using the procedures described in Example 502 and substituting ethyl 5-(2-tetrahydro-2H-pyran)-2-oxopentanoate for ethyl 3- 5 methylhexanoate afforded the title compound as an amorphous solid. 1 H NMR (CDCI3, 300 MHz) as a mixture of two diastereoisomers: δ 0.89 (t, J = 8.1 Hz, 3H), 0.89 (t, J = 8.1 Hz, 3H), 0.91 (t, J = 8.1 Hz, 3H), 0.91 (t, J = 8.1 Hz, 3H), 1.20-1.40 (m, 10H), 1.42-1.66 (m, 18H), 1.71 (brm, 2H), 1.85 (brm, 2H), 1 .96-2.23 (brm, 4H), 3.10-3.29 (m. 8H), 3.29-3.52 0 (m, 6H), 3.54-3.81 (m, 6H), 4.01 (q, J = 9 Hz, 2H), 4.12-4.25 (m, 4H), 4.43 (d, J = 9 Hz, 2H), 4.50 (d, J = 2.7 Hz, 2H), 5.94 (s, 2H), 5.95 (s, 2H), 6.76 (s, 2H), 6.76 (s, 2H), 6.81 (s, 1 H), 6.81 (s, 1 H). MS (APCI) (M+H)+ at m/e 517. Anal calcd for C29H44N206-1.4 TFA: C, 56.48; H, 6.77; N, 4.14. Found: C, 56.46; H, 6.99; N, 3.83. 5 Example 506 trans, trans-2- 12.2.4-Trimethyl-3-pentenvn-4-f 1 .3-benzodioxol-5- vn-1 -fN. N-dibutylaminocarbonylmethyn-pyrrolidine-3-carboxylic acid 0 Example 506A Methyl 3.3.5-trimethyl-4-hexenoate To a slurry of isopropyltripenylphosphonium iodide (20.5g, 47mmol) in 200mL of tetrahydrofuran was added n-butyllithium (27mL 5 of a 1.6M solution in hexane, 43mmol), and the solution was briefly warmed to 0°C After recooling, a solution of methyl 3,3-dimethyl-4- oxobutenoate (5.7g, 40mmol), prepared according to the procedure of Hudlicky et al., Synth. Commun., 16. 169 (1986) in 10mL of tetrahydrofuran was added, and the reaction was warmed to 0°C for 30min. The reaction was quenched with dilute hydrochloric acid, and partitioned with ethyl acetate. The organic layer was washed with water, and brine, dried with anhydrous magnesium sulfate, filtered, and the solvent was removed under reduced pressure. The residue was purified by flash chromatography on silica gel eluting with 10% ethyl acetate in hexanes to give 2.1g (30%) of the title compound. Example 506B trans, frans-2-f 2.2.4-Trimethyl-3- p entenvn-4-f 1 .3-benzodioxol-5- yn-1 -fN.N-dibutylaminocarbonylmethyn-pyrrolidine-3-carboxylic acid Using the procedures described in Example 502 and substituting methyl 3,3,5-trimethyl-4-hexenoate for ethyl 3-methylhexanoate afforded the title compound, which was isolated by lyophilization from dilute aqueous TFA/CH3CN. 1 H NMR (CDCI3, 300 MHz) δ 0.92 (t, J=7.2 Hz, 3H), 0.94 (t, J=7.2 Hz, 3H), 1.11 (s, 3H), 1.13 (s, 3H), 1.24-1.37 (m, 4H), 1.46-1.59 (m, 4H), 1.61 (d, J=1.2 Hz, 3H), 1.69 (d, J=1.2 Hz, 3H), 2.04-2.11 (m, 2H), 3.10-3.20 (m, 2H), 3.30-3.39 (m, 3H), 3.67-3.82 (m, 2H), 3.95-4.08 (m, 1 H), 4.32 (m, 2H), 4.37-4.47 (m, 1 H), 4.99 (s, 1 H), 5.95 (s, 2H), 6.73 (d, J=7.8 Hz, 1 H), 6.78 (dd, J=8.4, 1.2 Hz, 1 H), 6.84 (d, J=1.2 Hz, 1H). MS (DCI/NH3) m/e 515 (M+H) + . Anal calcd for C30H46N2θ5 « 1.05 TFA: C, 60.77; H, 7.48; N, 4.42. Found: C, 60.83; H, 7.20; N, 4.43. Example 507 trans. trans-2-(2.2.-Dimethyl-2-f 1 .3-dioxolan-2-ynethvn-4-f 1 .3- benzodioxol-5-vn-1 -fN . N-dibutylaminocarbonylmethyn-pyrrolidine-3- carboxylic acid Example 507A Methyl 3.3-dimethyl-3-f 1 .3-dioxolan-2-vnpronannatft Methyl 3,3-dimethyl-4-oxobutanoate (10g, 70mmol), prepared according to the procedure of Hudlicky et al., Synth. Commun., 1j6_ 169 (1986), was dissolved in 40mL of benzene, followed by addition of ethylene glycol (20mL), and p-toluenesulfonic acid monohydrate (1.3g). The reaction was refluxed with azeotropic removal of water for 1 hour. The reaction was poured into 200mL of ether, washed with saturated o sodium bicarbonate, water and brine, dried with anhydrous magnesium sulfate, filtered, and the solvent was removed under reduced pressure to give 12.4g (94%) of the title compound. Example 507B 5 trans. frans-2-f2.2.-Dimethyl-2-f 1 .3-dioxolan-2-ynethvn-4-f 1 .3- benzodioxol-5-yn-1 -fN. N-dibutvlaminocarbonylmethyn-ρyrrolidine-3- carboxylic acid Using the procedures described in Example 502 and substituting 0 methyl 3,3-dimethyl-3-(1 ,3-dioxolan-2-yl)propanoate for ethyl 3- methylhexanoate afforded the title compound, which was isolated by lyophilization from dilute aqueous TFA/CH3CN. 1 H NMR (CDCI3, 300 MHz) δ 0.82-1.00 (m, 12H), 1.24-1.40 (m, 4H), 1.43-1.64 (m, 5H), 1.76- 1.84 (m, 1 H), 2.93-3.00 (m, 1 H), 3.15-3.47 (m, 6H), 3.60-3.70 (m, 3H), 5 3.74-3.95 (m, 5H), 4.48 (s, 1 H), 5.94 (m, 2H), 6.72 (d, J=8.0 Hz, 1 H), 6.83 (dd, J=8.0, 1.2 Hz, 1 H), 6.94 (d, J=1.2 Hz, 1 H). MS (DCI/NH3) m/e 533 (M+H) + . Anal calcd for C29H44N2O7 -1.1 TFA-0.2 H2O: C, 56.63; H, 6.93; N, 4.23. Found: C, 56.60; H, 6.96; N, 4.25. 0 Example 508 frans. frans-2-f 2-f 1 .3-Dioxo-2-vnethvn-4-f 1 .3-benzodioxol-5-vn-1 - rr/V-4-heptyl-Λ/-f2-methyl-3-fluorophenvm amino carbonylmethyl]- pyrrolidine-3-carboxylic acid Example 508A 4-Heptanol To an ice cooled solution of 1.14g (10.0 mmol) of 4-heptanone in 20 mL of diethyl ether was added 370 mg (10.0 mmol) of UAIH4, in portions to keep ether reflux at a minimum. After 45 minutes, the reaction was quenched by sequential dropwise addition of 0.4 mL H2O, 0.4 mL 15% {wlv) NaOH(aσ), and 1.2 mL H2O. After stirring another 45 minutes, MgS04 was added until the salts were free flowing, then the reaction was filtered. The salts were washed with diethyl ether (3 x 5 mL), then the filtrate and washings were concentrated to a colorless oil. Yield 1.16g (100%). Example 508B 4-Methanesulfonyloxyheptane To an ice cooled solution of 834 mg (7.19 mmol) of 4-heptanol in 35 mL of CH2CI2 was added 1.5 mL of triethylamine. Next, 0.7 mL (9 mmol) of methanesulfonyl chloride was added, dropwise, over 1 minute. The mixture was stirred at 0 °C for 30 minutes, then extracted with H2O (1 x 15 mL), 5% NH4OH (2 x 15 mL), 1M HCl (2 x 15 mL), and brine (1 x 15 mL), dried over MgS04, filtered, and concentrated to an oil. Yield 1.31g (94%). 1 H NMR (300 MHz, CDCI3) d 0.96 (t, 6, J = 9), 1.43 (m, 4), 1.64 (m, 4), 3.00 (s, 3), 4.73 (quintet, 1 J = 5). Example 508C 4-Fluoro-3-methyl aniline To a solution of 20g (129 mmol) of 2-fluoro-5-nitrotoluene in 400 mL of ethanol was added 2g of 10% Pd-C The mixture was shaken under 45 P.S.I. H2 until hydrogen uptake ceased. The catalyst was filtered away and washed with ethanol, then the combined filtrate and washings were concentrated to 15.2 g (94%) of a colorless oil. Example 508D Λ/-Heptyl-4-fluoro-3-methylaniline To a solution of 4.10 g (3.28 mmol) of 4-fluoro-3-methylaniline in 30 mL of acetonitrile was added 7.64 g (3.93 mmol) of 4- methanesulfonyloxyheptane, and 3.4 g (4.1 mmol) of NaHCθ3(s). The mixture was stirred at reflux for 24 hours, then poured into 150 mL of H2O and extracted with diethyl ether (2 x 30 mL). The combined ether layers were back extracted with brine (1 x 30 mL), dried over MgSθ4, filtered, and concentrated to an oil. This was purified via silica gel chromatography, eluting with 97.5: 2.5 hexanes: ethyl acetate, to give 2.56g (35%) of a pale yellow oil. Example 508E Λ/.Λ/-f4-Heptvn-f4-fluoro-3-methynphenylbromoacetamide To an ice cooled solution of 4.88g (21.9 mmol) of N-(4-heptyl)-4- fluoro-3-methylaniline and 4.9 mL (61 mmol) of pyridine in 100 mL of toluene was added a solution of 4.90 mL (56.2 mmol) of bromoacetyl bromide in 7 mL of toluene. The solution was stirred for 24 hours, gradually warming to 25 °C, then extracted with 1 M HCl (1 x 100 mL). The aqueous layer was back extracted with diethyl ether (1 x 50 mL), then the combined organic layers were washed with H2O (2 x 50 mL), saturated NaHCθ3(ao;) (2 x 50 mL), and brine (1 x 50 mL), dried over MgS04, filtered, and concentrated in vacuo to an oil. This was purified via silica gel chromatography, eluting with 90:10 hexanes: ethyl acetate to give 7.48g (99%) of a light yellow oil. 1 H NMR (300 MHz, CDCI3) d 0.94 (t, 6, J = 5), 1.33 (m, 4), 1.43 (m, 4), 2.30 (s, 1.5), 2.31 (s, 1.5), 3.54 (s, 2), 4.72 (quintet, 1 , J = 5), 6.96-7.04 (m, 2), 7.07(d, 1 , J = 7). Example 508F frans.frans-2-f 2-f 1 .3-Dioxol-2-vnethvn-4-f 1 .3-benzodioxol-5-yn- 1 - ff/V-4-heptyl-/V-f2-methyl-3-fluorophenvni amino carbonylmethyP- pyrrolidine-3-carboxylic acid Using the procedures described in Example 502, substituting ethyl 5-(1 ,3-dioxolyl)-2-oxopentanoate for ethyl 3-methylhexanoate and Λ/,Λ -(4-heptyl)-(4-fluoro-3-methyl)phenyl-bromoacetamide for Λ ,Λ/-dibutyIbromoacetamide afforded the title compound as an amorphous solid. 1 H NMR (CDCI3, 300 MHz) δ 0.93 (brt, 6H), 1.23-1.47 (m, 8H), 1.67-2.10 (m, 4H), 2.32 (s, 3H), 3.16 (t, J = 9.0 Hz, 1 H), 3.52- 3.67 (brm, 2H), 3.73 (t, J = 9.0 Hz, 1 H), 3.81-4.02 (m, 6H), 4.13 (brm, 1 H), 4.72 (quintet, J = 6.9 Hz, 1H), 4.86 (t, J = 4.0 Hz, 1 H), 5.93 (s, 2H), 6.72 (d, J = 8.1 Hz, 1 H), 6.78 (dd, J = 1.8 Hz, 8.1 Hz, 1 H), 6.85 (d, J = 1.8 Hz, 1 H), 6.96 (m, 2H), 7.08 (t, J = 9.0 Hz, 1 H). MS (DCI/NH3) (M+H)+ at m/e 599. Anal Calcd for C33H43N2O7F-0.8 TFA: C, 60.24; H, 6.40; N, 4.06. Found: C, 60.21; H, 6.14; N, 3.86. Example 509 frans. frans-2-(2-f 1 .3-Dioxol-2-vnethvn-4-f 1 .3-benzodioxol-5-yn- 1 - (N.N-dibutylaminocarbonylmethyn-pyrrolidine-3-carboxylic acid Using the procedures described in Example 502, substituting ethyl 5- (1 ,3-dioxolyl)-2-oxopentanoate for ethyl 3-methylhexanoate and 6- methoxypiperona! for piperonal afforded the title compound as an amorphous solid. 1 H NMR (CDCI3, 300 MHz) δ 0.93 (t, J = 7.8 Hz, 3H), 0.95 (t, J = 7.8 Hz, 3H), 1.31 (m, 4H), 1.53 (m, 4H), 1.90 (m, 2H), 2.09 (m, 2H), 3.19 (dd, J = 8.4 Hz, 8.4 Hz, 2H), 3.30 (q, J = 9.6 Hz, 2H), 3.25- 3.42 (m, 1 H), 3.73 (q, J = 10.5 Hz, 1 H), 3.78-3.94 (m, 4H), 3.88 (s, 3H), 3.96 (dd, J = 5.1 Hz, 6.0 Hz, 1 H), 4.03 (dd, J = 3.0 Hz, 6.3 Hz, 2H), 4.33 (m, 3H), 4.87 (t, J = 3.6 Hz, 1H), 5.94 (s, 2H), 6.53 (d, J = 1.8 Hz, 1 H), 6.63 (d, J = 1.8 Hz, 1 H). MS (DCI/NH3) (M+H)+ at m/e 535. Anal calcd for C28H42N2O8-1.05 TFA: C, 55.25; H, 6.63; N, 4.28. Found: C, 55.39; H, 6.66; N, 4.26. Example 510 frans.frans-2-ff2-Methoxvphenoxv)-methvn-4-f 1 .3-benzodioxol-5-yn- 1 -fN.N-dibutylaminocarbonylmethvn-pyrrolidine-3-carboxylic acid Using the procedures described in Example 502, substituting o- methoxyphenoxyacetic acid for 3-methylhexanoic acid, the above compound was prepared as an amorphous solid. 1 H NMR (CDCI3, 300 MHz) δ 0.85 (t, J=7Hz, 3H), 0.90 (t, J=7Hz, 3H), 1.15-1.35 (m, 4H), 1.40- 1.55 (m, 4H), 3.05-3.25 (m, 4H), 3.28-3.55 (m, 4H), 3.58-3.68 (m, 1 H), 3.75-3.80 (m, 1 H), 3.82 (s, 3H), 3.91 (d, J=14Hz, 1 H), 4.05-4.15 (m, 1 H), 4.23-4.33 (m, 1 H),5.91 (s, 2H), 6.70 (d, J=8Hz, 1 H), 6.82-6.85 (m, 5H), 7.03 (s, 1H). MS (DCI/NH3) (M+H)+ at m/e 541. Anal calcd for C30H40N2O7: C, 66.65; H, 7.46; N, 5.18. Found: C, 66.37; H, 7.61 ; N, 5.09. Example 51 1 C.?S.3f?.4S)-2-f2.2-Dimethylpentvn-4-f 1 .3-benzodioxol-5-vn-1 -f N-4- heρtyl-N-f4-fluoro-3-methylphenyn aminocarbonylmethyn- pyrrolidine-3-carboxylic acid Example 511 A trans. trans-N- ferf-Butoxycarbonyl-2-f 2.2-dimethy I pentyl -4-f 1 .3- benzodioxol-5-yn-pyrrolidine-3-carboxylic acid Ethyl trans, frans-2-(2,2-dimethylpentyl)-4-( 1 ,3-benzodioxol-5- yl)-pyrrolidine-3-carboxylate (2.5g, 6.9mmol), prepared according to Example 503, was dissolved in 50mL of methylene chloride and di-ferf- butyldicarbonate (1.5g) was added. After stirring overnight at room temperature, the solvent was removed under reduced pressure and the residue was purified by flash chromatography on silica gel eluting with 10% ethyl acetate/hexanes to give the ethyl ester of the title compound (2.8g) as a colorless oil. The ester was dissolved in 50mL of ethanol followed by addition of sodium hydroxide (10mL of a 5M aqueous solution). After stirring for 20 hours at room temperature, the solvent was removed under reduced pressure, and the residue was dissolved in 150mL of water, and acidified with concentrated phosphoric acid. The mixture was extracted with chloroform (3X50mL), and the organic layers were washed wiith brine, dried over anhydrous magnesium sulfate, filtered, and the solvent was removed under reduced pressure to give the title compound (2.4g) as a white foam. Example 511 B Methyl trans. frans-2-f2.2-dimethylpentvn-4-f 1 .3-benzodioxol-5-yn- 1 -fN-4-heptyl-N-f4-fluoro-3-methylphenyl^aminocarbonylmethyl)- pyrrolidine-3-carboxylate: As a single enantiomer The product from Example 510A (1.97g, 4.5 mmol) was dissolved in 20mL of THF and cooled to 0°C, followed by addition of DMF (0.017mL, 5%), and oxalyl chloride (0.437mL, 5.00mmol). After 1 hour, solvent was removed at 0°C under a stream of nitrogen. The residue was dissolved in 5mL of benzene and evaporated. In a separate flask, (S)-4-benzyl-2-oxazolidinone (1.2g, 6.8mmol) was dissolved in 30mL of THF followed by addition of n-butyllithium (4.0mL of a 1.6M solution in hexanes) at 0°C, and the slurry was stirred for 15min. The acid chloride was dissolved in 20mL of THF and cooled to 0°C, followed by dropwise addition of the lithium oxazolide suspension via cannula. After 30min, the reaction was partitioned between ether and saturated bicarbonate. The organic phase was washed with water then brine, dried over anhydrous magnesium sulfate, filtered, and the solvent was removed under reduced pressure. The residue was purified by flash chromatography on silica gel eluting with 15% ethyl acetate/hexanes to give the undesired diastereomer (1.17g, 43%), then elution with 20% ethyl acetate/hexanes gave the desired diastereomer (1.04g, 38%). The desired diastereomer of the N-acyloxazolidinone (0.84g, 1.42mmol) was dissolved in 2.5mL of dichloromethane, and 2.5mL of trifluoroacetic acid was added. After 30min, the volatiles were removed under a stream of nitrogen, and the residue was twice dissolved in 5mL of toluene and evaporated under reduced pressure. The TFA salt was stirred with 4mL of acetonitrile followed by addition of diisopropylethyl amine (1.0mL, 5.7mmol), and N-4-heptyl- N-(4-fluoro-3-methylphenyl)bromoacetamide (589mg, 1.7mmol) as a solution in 2mL of acetonitrile. After 21 hours, the reaction was warmed to 50°C for 3.5 hours. The reaction was cooled, the solvent removed under reduced pressure, and the residue was purified by flash chromatography on silica gel eluting with 20-30% ethyl acetate/hexanes to give 0.939g of amide as a colorless oil. The above amide (200mg, 0.26mmol) was dissolved in 2.0mL of THF and 0.7mL of water. Solid lithium hydroxide monohydrate (22mg, 0.53mmol) was added at 0°C, followed by 30% hydrogen peroxide (0.050mL, 0.55mmol). After 1 hour, the reaction was warmed to room temperature. After an additional hour, the reaction was partitioned between 1 :1 ethyl acetate:hexanes and water, 0.15g of sodium thiosulfate was added and the mixture was mixed thoroughly. The organic layer was washed with water and brine, dried over anhydrous magnesium sulfate, filtered, and the solvent was removed under reduced pressure. The crude residue was dissolved in 2mL of ether, and 1mL of methanol. A solution of (trimethylsilyl)diazomethane in hexanes was added dropwise until the yellow color remained. The reaction was quenched by addition of 2 drops of glacial acetic acid, and the solvent was removed under reduced pressure. The residue was purified by flash chromatography on 10g of silica gel eluting with 15- 20% ethyl acetate/hexanes to give 70mg of the title compound as a crystalline solid (mp137.5°C). Example 511C (2S.3R.4S)-trans. frans-2-f 2.2-Dimethy lpentyl )-4-f 1 .3-benzodioxol- 5-yh- 1 -f N-4-heptyl-N-f4-fluoro-3- methylphenyl aminocarbonylmethyn-pyrrolidine-3-carboxylate The product from Example 510B (65mg, O.IOmmol) was dissolved in 1.0mL of methanol and sodium hydroxide (0.1 mL of a 5M aqueous solution) was added. After 2 hours, the reaction was warmed to reflux. After 6 hours, the reaction was cooled, and the solvent was removed under reduced pressure. The residue was dissolved in water and acidified with concentrated phosphoric acid. The aqueous solution was washed with chloroform (3X5mL), which was then washed with brine, dried with anhydrous magnesium sulfate, filtered and evaporated under reduced pressure. The title compound was isolated by lyophilization from dilute aqueous TFA/CH3CN. 1 H NMR (CDCI3, 300 MHz) d 0.78-0.95 (m, 15H), 1.04-1.46 (m, 12H), 1.76-2.95 (m, 2H), 2.31 (s, 3H), 3.23-3.33 (m, 1H), 3.47-3.58 (m, 1 H), 3.6-3.75 (m, 2H), 3.80-3.95 (m, 2H), 4.05- 4.15 (m, 1 H), 4.73 (m, 1 H), 5.94 (s, 2H), 6.70-6.80 (m, 2H), 6.82-6.93 (m, 2H), 6.96-7.14 (m, 2H). MS (DCI/NH3) m/e 597 (M+H) + . Anal calcd for C35H49N2FO5 -0.05H2O *0.8TFA: C, 63.81 ; H, 7.30; N, 4.07. Found: C, 63.84; H, 7.18; N, 3.94. [a]^ 1 =+46° (c 2.7g/L, CHCI3) Example 512 frans. frans-2-f 2-f 2-Oxopyrrolidi n-1 -ynethylY4-f 1 .3-benzodioxol-5- yn-1 -fN.N-dibutylaminocarbonylmethvn-pyrrolidine-3-carboxylic acid Example 512A 2-Oxopyrrolidin-1-ylpropionic acid To a stirred solution of 5.0 mL (40.5 mmol) 2-oxopyrrolidin-1- ylpropionitrile in 15 mL of dioxane was added 8.1 mL of hydrochloric acid, a 6.0 M aqueous solution. The resulting mixture was then refluxed at 10 °C over night. The reaction mixture was then allowed to cool to room temperature, extracted with methylene chloride three times. The extracts were combined and washed with saturated brine solution once, dried over anhydrous sodium sulfate, filtered and evaporated under reduced pressure to give 1.60 g (25%) of acid as a brown oil. Example 512B Ethyl 5-f2-oxopyrrolidin-1-yn-3-oxopentanoate The title compound was prepared from the above acid by adapting the method of Bram and Vilkas, Bui. Chem. Soc. Fr., 945 (1964). Example 512C frans. frans-2-(2-f 2-Oxopyrrolidin-1 -ynethvn-4-( 1 .3-benzodioxol-5- vn-1 -fN.N-dibutylaminocarbonylmethvn-pyrrolidine-3-carboxylic acid Using the procedures described in Example 502, substituting ethyl 5-(2-oxopyrrolidin-1 -yl)-3-oxopentanoate for ethyl 3- methylhexanoate afforded the title compound as an amorphous solid. H NMR (CDCI3, 300 MHz) δ 0.01 (t, J = 7.5 Hz, 3H), 0.94 (t, J = 7.5 Hz, 3H), 1.23-1.38 (m, 4H), 1.44-1.60 (m ,4H), 2.05 (t, J = 6.9 Hz, 2H), 2.12- 2.25 (m, 1H), 2.38 (td, J = 4.2 Hz, 8.4 Hz, 2H), 2.47-2.61 (m, 1H), 3.17 (dd, J = 6.0 Hz, 8.7 Hz, 2H), 3.24 (t, J = 9 Hz, 1 H), 3.32 (t, J = 7.8 Hz, 2H), 3.38-3.48 (m, 3H), 3.52 (t, J = 9 Hz, 1H), 3.66 (t, J = 6.9 Hz, 1 H), 3.96 (m, 2H), 4.14 (m, 1 H), 4.38 (brs, 2H), 5.93 (s, 2H), 6.74 (d, J = 8.1 Hz, 1 H), 6.89 (dd, J = 1.8 Hz, 8.1 Hz, 1 H), 6.87 (d, J = 1.8 Hz, 1 H). MS (DCI/NH3) (M+H)+ at m/e 516. Anal calcd for C28H41 N306-1.4 TFA: C, 54.78; H, 6.33; N, 6.22. Found: C, 54.69; H, 6.33; N, 6.14. Example 513 frans. frans-2-f2-f 1 .3-Dioxol-2-ynethvn-4-f 7-methoxy-1 .3- benzodioxol-5-vn- 1 -f N-4-heptyl-N-f4-fluoro-3- methylphenyl^aminocarbonylmethvn-pyrrolidine-3-carboxylic acid Using the procedures described in Example 502, substituting ethyl 5-(1 ,3-dioxolyl)-2-oxopentanoate for ethyl 3-methylhexanoate, N-4-heptyl-N-(4-fluoro-3-methylphenyl) bromoacetamide for N,N- dibutyl bromoacetamide and 6-methoxypiperonal for piperonal afforded the title compound as an amorphous solid. 1 H NMR (CDCI3, 300 MHz) δ 0.93 (br t, 6H), 1.23-1.47 (m, 8H), 1.67-2.10 (m, 4H), 2.32 (s, 3H), 3.16 (t, J = 9 Hz, 1 H), 3.60-4.03 (m, 8H), 3.88 (s, 3H), 4.21 (brs, 1 H), 4.72 (quintet, J = 6.6 Hz, 1 H), 4.86 (t, J = 3.6 Hz, 1 H), 5.93 (s, 2H), 6.49 (s, 1 H), 6.61 (s, 1 H), 6.96 (m, 2H), 7.08 (t, J = 9 Hz, 1 H). MS (DCI/NH3) (M+H)+ at m/e 629. Anal calcd for C34H45N2O8F.I .O TFA: C, 58.21 ; H, 6.24; N, 3.77. Found: C, 58.11 ; H, 6.11 ; N, 3.58. Example 514 frans. frans-2-f 2.2-Dimethylpentyn-4-f7-methoxy- 1 .3-benzodioxol-5- vn-1 -fN.N-dibutylaminocarbonylmethvn-pyrrolidine-3-carboxylic acid Using the procedures described in Example 502, substituting ethyl 5-methyl-3-oxooctanoate for ethyl 3-methylhexanoate and 6- methoxypiperonal for piperonal afforded the title compound as an amorphous solid. 1 H NMR (CDCI3, 300 MHz) δ 0.81 (s, 3H), 0.84 (s, 3H), 0.86 (t, J = 6.9 Hz, 3H), 0.93 (t, J = 6.9 Hz, 3H), 0.96 (t, J = 6.9 Hz, 3H), 1.09-1.38 (m, 8H), 1.45-1.59 (m, 4H), 1.84-2.00 (m, 2H), 3.15 (dd, J = 6.9 Hz, 10.0 Hz, 2H), 3.30-3.42 (m, 3H), 3.72 (t, J = 10.5 Hz, 1 H), 3.86 (t, J = 10.5 Hz, 1 H), 3.88 (s. 3H), 4.02 (q, J = 10.0 Hz, 1 H), 4.12 (d. J = 16.8 Hz. 1 H), 4.29 (d, J = 16.8 Hz, 1H), 4.41 (brm, 1H), 5.84 (s, 1 H), 6.52 (d, J = 1.8 Hz, 1 H), 6.67 (d, J = 1.8 Hz, 1H). MS (DCI/NH3) (M+H)+ at m/e 533. Anal calcd for C30H48 2O6O.9 TFA: C, 60.12; H, 7.76; N, 4.41. Found: C, 60.18; H, 7.62; N, 4.33. Example 515 frans. frans-2-f 2.2-dimethylpentvn-4-f 2.3-dihyd ro-benzof uran-5-vn- 1 -fN.N-dibutylaminocarbonylmethyn-pyrrolidine-3-carboxylic acid Using the procedures described in Example 502, substituting ethyl 3,3-dimethylhexanoate for ethyl 3-methylhexanoate and 2,3- dihydro-benzofuran-5-carbaldehyde for piperonal afforded the title compound as an amorphous solid by lyophylization with CH3CN/TFA/H2O. 1 H NMR (300 MHz, CDCI3) δ 0.83 (s, 3H), 0.85 (s, 3H), 0.86 (t, J=7.2 Hz, 3H), 0.92 (t, J=7.2 Hz, 3H), 0.95 (t, J=7.2 Hz, 3H), 1.09-1.39 (m, 8H). 1.44-1.59 (m, 4H), 1.88 (dd, J=15.0, 7.2 Hz, 1H), 2.00 (d, J=15.0 Hz, 1 H), 3.09 (m, 2H), 3.18 (t, J=9.0 Hz, 2H), 3.27-3.38 (m, 3H), 3.65-3.95 (m, 2H), 4.05 (q, J=10.0 Hz, 1 H), 4.18 (d, J=16.8 Hz, 1 H), 4.30-4.45 (m, 2H), 4.55 (t, J=9.0 Hz, 2H), 6.70 (d, J=8.4 Hz, 1H), 7.04 (dd, J=8.4, 2.1 Hz, 1 H), 7.23 (brs, 1 H). MS (DCI/NH3) at m/e 501 (M+H)+. Anal calc'd for C30H48N2O4 LO5 TFA: C, 62.14; H, 7.97; N, 4.51. Found: C, 62.19; H, 8.00; N, 4.43. Example 516 frans. frans-2-f 2.2.-Dimethyl-2-( 1 .3-dioxolan-2-ynethvn-4-f 1 - methoxy- 1 .3-benzodioxol-5-yn-1 -fN. N-dibutylaminocarbonylmethyn- pyrrolidine-3-carboxylic acid Using the procedures described in Example 502, substituting methyl 3,3-dimethyl-3-( 1 ,3-dioxolan-2-yl)propanoate for ethyl 3- methylhexanoate and 6-methoxypiperonal for piperonal afforded the title compound as an amorphous solid by lyophylization with CH3CN/TFA/H2O. " > H NMR (CDCI3, 300 MHz) δ 0.93 (t, J=7.2 Hz, 3H), 0.94 (t, J=7.2 Hz, 3H), 0.95 (s, 3H), 0.96 (s, 3H), 1.31 (sextet, J=7.2 Hz, 4H), 1.45 (m, 4H), 1.93 (dd, J=15.9, 6.0 Hz, 1H), 2.13 (d, J=15.9 Hz, 1H), 3.20 (dd, J=7.7, 7.7 Hz, 1 H), 3.26-3.40 (m, 3H), 3.60 (m, 1 H), 3.75-3.86 (m, 3H), 3.88 (s, 3H), 3.93-4.01 (m, 3H), 4.00-4.11 (m, 1 H), 4.23 (d, J=15.9 Hz, 1 H), 4.37-4.48 (m, 2H), 4.49 (s, 1H), 5.94 (s, 2H), 6.51 (d, J=2.1 Hz, 1 H), 6.64 (d, J=2.1 Hz, 1H). MS (DCI/NH3) at m/e 563 (M+H)+. Anal calcd for C30H46N2O8 O.9 TFA: C, 57.41 ; H, 7.11 ; N, 4.21 ; found: C, 57.35; H, 6.86; N, 4.05. Example 517 frans.frans-2-f2-f2-Methoxvphenvn-ethvn-4-f 1 .3-benzodioxol-5-yn- 1-fN.N-dibutylaminocarbonylmethvn- p yrrolidine-3-carboxylic acid Using the procedures described in Example 502, substituting 0- methoxyphenylpropionic acid for 3-methylhexanoic acid, the above compound was prepared as an amorphous solid. 1 H NMR (CDCI3, 300 MHz) δ 0.85 (t, J=7Hz, 3H), 0.91 (t, J=7Hz, 3H), 1.10-1.27 (m, 4H), 1.42- 1.60 (m, 4H), 1.72-1.89 (m, 1 H), 1.91-2.02 (m, 1 H), 2.55-2.77 (m, 2H), 2.94 (t, J=6Hz, 1 H), 3.05-330 (m, 6H), 3.59-3.82 (m, 3H), 3.73 (d, J=14Hz, 1 H), 3.77 (s, 3H), 5.91 (s, 2H), 6.70 (d, J=8Hz, 1 H), 6.78-6.88 (m, 3H),6.92 (d, J=2Hz, 1 H), 7.08-7.19 (m, 2H). MS (DCI/NH3) (M+H)+ at m/e 539. Anal calcd for C31 H42N2O6: C, 69.12; H, 7.86; N, 5.20. Found: C, 68.89; H, 7.70; N, 4.99. Example 518 trans. frans-2-f2.2-Dimethyl-3-f E)-pentenyh-4-f 1 -methoxy- 1 .3- benzodioxol-5-yn-1 -fN .N-dibutylaminocarbonylmethyn-pyrrolidine-3- carboxylic acid Example 518A 4-Methyl-3-penten-2-ol To a stirred solution of 3-methyl-2-butenal (8.7g, 103mmol) in 100mL of tetrahydrofuran under N2 at 0 °C was added methylmagnesium bromide (38mL of a 3.0M solution in ethyl ether, 1 14mmol) dropwise. The resulting mixture was allowed to warm to room temperature slowly and stirred at room temperature for 1 hour before it was quenched with 25m L of saturated NH4CI. The resulting biphasic mixture was partitioned between ethyl ether and water. The organic layer was washed with brine, dried with anhydrous magnesium sulfate, filtered, and the solvent was removed under reduced pressure to give 8.4g (81 %) of alcohol as a colorless oil. Example 518B frans-Ethyl 3.3-dimethyl-4-pentenoate A mixture of 4-methyl-3-penten-2-ol (7.4g, 74mmol), triethyl orthoacetate (13.6mL, 74mmol) and propionic acid (0.28mL, 3.7mmol) was heated at 150 °C for 7 hours. The product was then distilled under normal pressure (200-220 °C) to give 5.0g of crude ester as a colorless oil. Example 518C trans. frans-2-f2.2-Dimethyl-3-f E)-pentenvn-4-f 1 -methoxy-1 .3- benzodioxol-5-vn-1 -f N .N-dibutylaminocarbonylmethyn-pyrrolidine-3- carboxylic acid Using the procedures described in Example 502, substituting frans-ethyl 3,3-dimethyl-4-pentenoate for ethyl 3-methylhexanoate and 6-methoxypiperonal for piperonal afforded the title compound as an amorphous solid by lyophilization from dilute aqueous TFA/CH3CN. H NMR (CDCI3, 300 MHz) δ 0.92 (t, J=7.2 Hz, 3H), 0.95 (t, J=7.2 Hz, 3H), 0.97 (s, 3H), 0.99 (s, 3H), 1.31 (sextet, J=7.2 Hz, 4H), 1.52 (quintet, J=7.2 Hz, 4H), 1.58 (d, J=5.4 Hz, 3H), 1.92 (dd, J=15.0, 6.6 Hz, 1 H), 2.04 (d, J=15.0 Hz, 1 H), 3.15 (dd, J=7.8, 7.8 Hz, 1H), 3.30-3.40 (m, 3H), 3.75 (m, 2H), 3.87 (s, 3H), 3.99 (q, J=9 Hz, 2H), 4.11-4.30 (m, 3H), 5.29 (d, J=15.6 Hz, 1 H), 5.38 (dd, J=15.6, 6 Hz, 1 H), 5.94 (s, 2H), 6.50 (d, J=1.8 Hz, 1H), 6.63 (d, J=1.8 Hz, 1H). MS (DCI/NH3) at m/e 531 (M+H)+. Analysis calc'd for C30H46N2O6 0.95 TFA: C, 59.95; H, 7.41 ; N, 4.38; found: C, 60.00; H, 7.33; N, 4.35. Example 519 trans. frans-2-f 3-f2-pyridvnethvn-4-f 1 .3-benzodioxol-5-vn- 1 -fN . N- dibutylaminocarbonylmethyn-pyrrolidine-3-carboxylic acid Example 519A 3-f2-Pyridvn-propionic Acid In a 50 mL round-bottomed flask equipped with a stirring bar was placed 3-(2-pyridyl)-propanol (1 g, 7.6 mmol), water (13 mL) and concentrated sulfuric acid (0.5 g, 5.1 mmol). To this stirred solution was added over a period of 30 min potassium permanganate (1.8 g, 11.3 mmol) while the reaction temperature was maintained at 50 °C After the addition was completed, the mixture was held at 50 °C until the color of the reaction mixture turned brown, then heated at 80 °C for 1 hour and filtered. The filtrate was evaporated to dryness to yield quantitatively the desired acid (1.14 g) suitable for next step without further purification. To prepare a pure acid, the residue thus obtained was boiled in ethanol (10 mL) in the presence of charcoal (0.1 g) for 5 min, filtered and cooled to give crystalline 3- (2-pyridyl)-propionic acid (0.88 g, 78%). Example 519B trans, frans-2-f 3-f 2-pyridynethyn-4-f 1 .3-benzodioxol-5-vn-1 -f N .N- dibutylaminocarbonylmethvn-pyrrolidine-3-carboxylic acid Using the procedure described in Example 502, the title compound was isolated by lyophilization from dilute aqueous TFA/CH3CN as an amorphous solid. 1 H NMR (CDCI3, 300 MHz) δ 8.65 (d, J=6.0 Hz, 1 H), 8.06 (t, J=6.91 Hz, 1 H), 7.70 (d, J=9.0 Hz, 1 H), 7.51 (t, J=6.91 Hz, 1 H), 6.82- 6.66 (m, 3H), 5.91 (s, 2H), 4.45 (s, 2H), 4.29-4.18 (m, 1 H), 4.04 (dd, J=20.1 , 10.5 Hz, 1 H), 3.84 (t, J=12.6 Hz, 1 H), 3.62 (dd, J=13.8, 9.6 Hz, 1 H), 3.46-3.13 (m, 7H), 2.51 (broad s, 2H), 1.60-1.43 (m, 4H), 1.37-1.22 (m, 4H), 0.91 (t, J=8.4 Hz, 6H). MS (DCI/NH3) m/e 510 (M+H) + . Anal calcd for C29H39N3θ5'1.75 TFA: C, 55.04; H, 5.79; N, 5.92. Found: C, 55.08; H, 5.64; N, 5.81. Example 520 (2S. 3R. 4S)-2-f2-f2-oxopyrrolidin- 1 -vnethvn-4-f 1 .3-benzodioxol-5- yn-1 -fN.N-dibutylaminocarbonylmethvn-pyrrolidine-3-carboxylic acid Example 520A (2S. 3R. 4S)-Ethyl-2-(2-f2-oxoPyrrolidin-1 -vhethvn-4-f 1 .3- benzodioxol-5-ynpyrrolidine-3-carboxylate-f S)-Mandelate The racemic amino ester from Example 512 (3.45g, 8.98mmol) in 10mL of ethyl acetate was treated with (S)-(+)-mandelic acid (0.75g, 4.93mmol). Upon the formation of the clear solution, hexane was dropped in slowly with stirring till the solution became light cloudy. The solution was left stirred at room temperature over night. The crystals was then collected by filtration, recrystalized from ethyl acetate/hexane twice to give a yield of 800 mg (17%) of pure salt. Example 520B (2S. 3R. 4SVEthyl-2-f2-f2-oxθPyrrolidin- 1 -ynethyn-4-f 1 .3- benzodioxol-5-vn-1 -fN . N-dibutylaminocarbonylmethvn-pyrrolidine-3- carboxylate To a stirred solution of pure mandelate (150 mg, 0.28 mmol) in CH3CN was added Λ/,Λ/-dibutylbromoacetamide(84 mg, 0.34 mmol) and diisopropylethylamine (88uL, 0.56mmol). The resulting mixture was stirred at room temperature over night. Solvent was then removed under reduced pressure and the crude product was purified by silica gel flash chromatography to give 140 mg (80% yield) of the title compound. Example 520C (2S. 3R. 4S)-2-(2-f2-oxopyrrolidin- 1 -ynethvn-4-f 1 .3-benzodioxol-5- vn-1 -f N.N-dibutylaminocarbonylmethvn-pyrrolidine-3-carboxylic acid Using the procedures described in Example 502, the title compound was prepared as an amorphous solid by lyophylization with CH3CNTFA/H2O. 1 H NMR (CDCI3. 300 MHz) δ 0.91 (t, J = 7.5 Hz, 3H), 0.94 (t, J = 7.5 Hz, 3H), 1.23-1.38 (m, 4H), 1.44-1.60 (m ,4H), 2.05 (t, J = 6.9 Hz, 2H), 2.12-2.25 (m, 1H), 2.38 (td, J = 4.2 Hz, 8.4 Hz, 2H), 2.47- 2.61 (m, 1 H), 3.17 (dd, J = 6.0 Hz, 8.7 Hz, 2H), 3.24 (t, J = 9 Hz, 1 H), 3.32 (t, J = 7.8 Hz, 2H), 3.38-3.48 (m, 3H), 3.52 (t, J = 9 Hz, 1 H), 3.66 (t, J = 6.9 Hz, 1 H), 3.96 (m, 2H), 4.14 (m, 1 H), 4.38 (brs, 2H), 5.93 (s, 2H), 6.74 (d, J = 8.1 Hz, 1 H), 6.89 (dd, J = 1.8 Hz, 8.1 Hz, 1 H), 6.87 (d, J = 1.8 Hz, 1 H). MS (DCI/NH3) (M+H)+ at m/e 516. Anal calcd for C28H41 3O6-0.85 TFA: C, 58.23; H, 6.89; N, 6.86. Found: C, 58.37; H, 6.90; N, 6.84. Example 521 <2S. 3R. 4Sι-2-(2-f2-oxo p yrrolidin- 1 -vnethyl )-4-n .3- benzodioxol-5-vn- 1 -f N-4-heptyl-N-f4-fluoro-3- methylphenyl^aminocarbonylmethvn-pyrrolidine-3-carboxylic acid Using the procedures described in Example 520, substituting N,N- (4-heptyl)-(4-fluoro-3-methyl)phenyl-bromoacetamide for N,N- dibutylbromoacetamide afforded the title compound as an amorphous solid by lyophylization with CH3CN/TFA/H2O. 1 H NMR (CDCI3, 300 MHz) δ 0.85-0.98 (m, 6H), 1.22-1.55 (m, 8H), 2.04 (quintet, J=7.9 Hz, 4H), 2.32 (s, 3H), 2.36 (t, J=7.9 Hz, 2H), 2.61 (m, 1 H), 3.14 (m, 1 H), 3.25-3.61 (m, 5H), 3.66-3.77 (m, 1 H), 3.79-3.90 (m, 2H), 3.92-4.03 (m, 1 H), 4.69 (quintet, J=6.8 Hz, 1 H), 5.95 (s, 2H), 6.71 (s, 2H), 6.78 (s, 1 H), 6.93-7.13 (m, 3H); MS (DCI/NH3) at m/e 610 (M+H)+. Anal calc'd for C34H44N3O6F1 I .45 TFA: C, 57.18; H, 5.91 ; N, 5.42. Found: C, 57.20; H, 5.62; N, 5.52. Example 522 trans. trans-2-(2-( 1 -pyrazolvnethvn-4-f 1 .3-benzodioxol-5-yn- 1 - fN. N-dibutylaminocarbonylmethvn-pyrrolidine-3-carboxylic acid Example 522A 3-f 1 -Pyrazolvn-propionic Acid In a 10 mL round-bottomed flask equipped with a condenser and a stirring bar was placed pyrazole (0.50 g, 7.3 mmol), acrylic acid (0.50 mL, 7.3 mmol) and triethylamine (3 mL). The reaction mixture was refluxed for 6 hours. After removing triethylamine, the viscous oil was dried on high vacuo during 12 hours to yield quantitatively the desired acid (1.0 g) suitable for the next step without further purification. Example 522B trans. trans-2-(2-( 1 -pvrazolvnethvn-4-f 1 .3-benzodioxol-5-vn-1 - fN.N-dibutylaminocarbonylmethvn-pyrrolidine-3-carboxylic acid Using the procedure described in Example 502, the title compound was isolated by lyophilization from dilute aqueous TFA/CH3CN as an amoφhous solid 1 H NMR (CDCI3, 300 MHz) δ 7.56 (d, J=3.0 Hz, 1 H), 7.50 (d, J=3 Hz, 1H), 6.83-6.66 (m, 3H), 6.28 (t, J=3 Hz, 1 H), 5.91 (s, 2H), 4.55-3.98 (m, 6H), 3.83-3.72 (t, J=10.5 Hz, 1H), 3.61-3.40 (t, J=10.5 Hz, 1 H), 3.36-3.12 (m, 5H), 2.69-2.43 (m, 2H), 1.59-1.42 (m, 4H), 1.38-1.21 (m, 4H), 0.91 (t, J=7.5 Hz, 6H). MS (DCI/NH3) at m/e 499 (M+H) + . Anal calcd for C-27H38N4O5O.75 TFA: C, 58.60; H, 6.69; N, 9.59. Found: C, 58.53; H, 6.45; N, 9.67. Example 523 trans. frans-2-(4-Methoxyphenyn-4-f 1 .3-benzodioxol-5-yn-1 -[fN- butyl-N-(3-hvdroxypropynammo^carbonylmethvπ-pyrrolidine-3- carboxylic acid Example 523A N-Butyl-N-f3-hvdroxypropyn-amine To a solution of 15.9g (100 mmol) of methyl 3-/V-(n- butyl)aminopropionate in 150 mL of diethyl ether at 0 'C was added 50 mL (0.35 mmol) of 1.0M UAIH4 in diethyl ether, keeping reflux at a minimum. The mixture was stirred at 0 'C for 2.25 hours, the quenched by sequential dropwise addition of 1.9 mL H2O, 1.9 mL 15%w/v NaOH(ag), and 5.7 mL H2O. After stirring for 30 min, the salts were filtered and washed with diethyl ether, then the filtrate was concentrated to 11.3 g (86%) of a light yellow oil. Example 523B N-Butyl-N-f3-hydroxypropyn-chloroacetamide To an ice cooled solution of 1.31g (10.0 mmol) of Λ/-butyl,/V-(3- hydroxypropyl)amine in 20 mL of ethyl acetate was added a solution of 1.71g (10.0 mmol) of chloroacetic anhydride in 10mL of ethyl acetate. The mixture was stirred, and gradually warmed to room termperature over 18 hours. The reaction was extracted with H2O (1 x 50 mL), saturated NaHCθ3 ( a q) (2 x 50 mL), and brine (1 x 50 mL), dried over MgSθ4, filtered, and concentrated to an oil. The product was purified via silica gel chromatography, eluting with 80:20 hexanes:ethyl acetate to give 723 mg (35%) of a light yellow oil. Example 523C trans, frans-2-f 4-Methoxyphenvn-4-f 1 .3-benzodioxol-5-vn-1 -[fN- butyl-N-(3-hvdroxyproρynamino^carbonylmethvH-ρyrrolidine-3- carboxylic acid Using the procedures described in Example 1D, substituting N- butyl-N-(3-hydroxypropyl)-chloroacetamide for N-propyl bromoacetamide and adding DMSO as cosolvent, afforded the title compound, which was isolated by lyophilization from dilute aqueous TFA/CH3CN. 1 H NMR (CD3OD, 300 MHz) δ 0.78-0.95 (m, 3H), 1.00-1.80 (m, 4H), 2.80-3.65 (m, 15H), 3.80 (d, J=1.5 Hz, 2H), 5.93 (s, 2H), 6.72- 7.05 (m, 5H), 7.33-7.40 (m, 2H). MS (DCI/NH3) at m/e 513 (M+H)+. Anal calc'd for C28H36N2θ7 « 1.6 H20: C, 62.12; H, 7.30; N, 5.17. Found: C, 62.04; H, 7.21 ; N, 4.88. Example 524 trans. frans-2-(4-MethoxyphenylY4-( 1 .3-benzodioxol-5-vn-1 -[fN- propyl-N-propoxyamino)carbonylmethvn-pyrrolidine-3-carboxylic acid Example 524A N-Boc-O-allylhvdroxylamine O-Allylhydroxylamine hydrochloride hydrate (5.0g) was dissolved in THF (15 mL). The solution was cooled to 0°C in an ice bath. Diisopropylethylamine (8mL) and di-t-butyldicarbonate (10.0g) were added. The mixture was stirred at 0°C for 1 hour at which point the bath was removed and the reaction allowed to warm to room temperature and stirred overnight. The THF was removed in vacuo and the residue taken up in EtOAc (25 mL), and washed with water (1 x 50 mL), saturated sodium bicarbonate solution (3 x 50 mL), 1 N phosphoric acid (3 x 50 mL), and brine (1 x 50 mL). The organic layer was dried with sodium sulfate and evaporated to give a light yellow oil (6.5g) which was used without any further purification. Example 524B N-Boc-N-propyl-O-allylhydroxyl amine N-Boc-O-allylhydroxylamine (6.5g) from the above procedure was dissolved in dry THF (25 mL) and the solution cooled to 0°C in an ice bath. Sodium hydride (1.5g, 60% dispersion in oil) was added portionwise over 5 min. The resulting mixture was stirred for 30 min at 0°C 1-lodopropane (3.8mL) was added dropwise to the mixture. The reaction was stirred at 0°C for 1 hour, then stirred overnight at room temperature. The THF was removed in vacuo and the residue taken up in EtOAc (50 mL) and washed with water (1 x 50 mL), saturated sodium bicarbonate solution (3 x 50 mL), 1N phosphoric acid (3 x 50 mL), and brine (1 x 50 mL). The organic layer was dried with sodium sulfate and evaporated to give a light yellow oil, which was purified by flash chromatography on silica gel eluting with 5% EtOAc/hexanes to give the title compound as a colorless oil (6.0g). Example 524C N-Boc-N-propyl-N-propoxyamine N-Boc-N-propyl-O-allylhydroxylamine (6.0g) was dissolved in EtOAc (100 mL). 10% Palladium-on-carbon (0.5g) was added, and the mixture was purged with nitrogen. The nitrogen line was exchanged for a balloon of hydrogen, and the mixture was stirred at room temperature for 6 hours. The catalyst was removed by filtration through a pad of Celite and the solvents were removed in vacuo to give a yellow oil which was purified by flash chromatography on silica gel eluting with 5% EtOAc/hexanes to give the title compound as a colorless oil (5.8g). Example 524D N-Propyl-N-propoxyamine hydrochloride N-Boc-N-propyl-N-propoxyamine (5.8g) was dissolved in 4N HCI/dioxane (10mL) and stirred at room temperature for 7 hours. The solvent was removed in vacuo and the residue triturated with diethyl ether. The resulting yellow solid (2.1 g) was collected by filtration and washed with diethyl ether. Example 524E N-propyl-N-propoxy-bromoacetamide N-Propyl-N-propoxyamine hydrochloride (0.30 g) was dissolved in acetonitrile and cooled to -20°C Pyridine (0.2 mL) was added. Bromoacetyl bromide (0.15g) was added dropwise over 5 min. The solution was stirred at -20°C for 30 min. The bath was removed and the solution was stirred for 6 hours at room temperature. The solvent was removed in vacuo and the residue taken up in EtOAc (50 mL) and washed with water (1 x 25 mL), 1 N phosphoric acid (3 x 25 mL), and brine (1 x 25 mL). The organic layer was dried with sodium sulfate and evaporated to give a dark orange oil (0.35g). The product is a mixture of chloro- and bromoacetamides in a ratio of -3:1. Example 524F trans, frans-2-f 4-Methoxyphenyn-4-f 1 .3-benzodioxol-5-yn-1-ffN- butyl-N-f3-hvdroxypropynamino)carbonylmethyl1-pyrrolidine-3- carboxvlic acid Prepared according to the procedure of Example 523C, employing N-propyl-N-propoxy-bromoacetamide and ethyl 2-(4-methoxyphenyl)- 4-(1 ,3-benzodioxol-5-yl)-pyrrolidine-3-carboxylate. The crude product was purified by preparative HPLC (Vydac mC18) eluting with a 10-70% gradient of CH3CN in 0.1% TFA. The appropriate fraction was lyophilized to give the product as a white solid. 1 H NMR (CDCI3, 300 MHz) δ 0.87 (m, 6H, J=8Hz), 1.49 (m, 2H, J=8Hz), 1.61 (m, 2H, J=8Hz), 3.55 ( , 6H), 3.80 (m, 2H), 3.81 (s, 3H), 4.00 (m, 2H), 4.13 (d, 2H, J=17Hz), 5.96 (s, 2H), 6.77 (d, 1H, J=9Hz), 6.90 (m, 3H), 7.05 (d, 1 H, J=1Hz), 7.44 (d, 2H, J=9Hz). MS (DCI/NH3) m/e 499 (M+H)+. Anal calcd for C27H34N2O7 • 1.20 TFA: C, 55.57; H, 5.58; N, 4.41. Found: C, 55.59; H, 5.58; N, 4.55. Example 525 trans. frans-2-(4-Methoxyphenyn-4-f 1 .3-benzodioxol-5-vn-1 -rfN- butyl-N-propoxyamino)carbonylmethyl]-pyrrolidine-3-carboxylic acid Example 525A N-butyl-N-f2-hvdroxyethyn-amine In a thick walled glass tube 5 ml (100 mmol) of ethylene oxide was condensed at -78 ' C To this12.5 ml (120 mmol) of butylamine was added and the tube was sealed. The resultant solution was allowed to heat in an oil bath at 50 ' C for 18 hours. Unreacted reagents were removed by evaporation to give the title compound. Example 525B N-Butyl-N-f2-azidoethyn-chloroacetamide To 500 mg of N-butyl, N-2-hydroxyethylamine was added 2 mL of thinoyl chloride, dropwise. After the initial reaction had ceased, the reaction was stirred for 10 min, then concentrated to an oil. Diethyl ether was added and evaporated to aid in removal of the thionyl chloride. The residue was taken up in 10 mL of DMF, and 1.0g (16 mmol) of sodium azide was added. The reaction was stirred at 75 * C for 2 hours, then poured into 50 mL of 0.6M NaHCθ3(ag.) and extracted with diethyl ether (3 x 15 mL). The combined ether layers were back extracted with brine (1 x 15 mL), dried over MgSθ4, and filtered. To the ether solution was added 850 mg (4.97 mmol) of chloroacetic anhydride. The reaction was stirred for 10 min, then concentrated to an oil. This was taken up in 10 mL of saturated NaHCθ3(ag.) and extracted with diethyl ether (3 x 5 mL). The combined ether layers were back extracted with brine (1 x 5 mL), dried over MgSθ4, filtered, and concentrated to an oil. This was purified via silica gel chromatography, eluting with 30% ethyl acetate: hexanes, to give 161 mg (17%) of an oil. Example 525C trans, frans-2-f 4-Methoxyphenyn-4-f 1 .3-benzodioxol-5-yn-1 -ffN- butyl-N-f2-aminoethynamino^carbonylmethyn-pyrrolidine-3- carboxylic acid According to the procedure of Example 523C, N-butyl-N-(2- azidoethyl)-chloroacetamide was coupled with ethyl 2-(4- Methoxyphenyl)-4-(1 ,3-benzodioxol-5-yl)-pyrrolidine-3-carboxylate. The crude product was chromatographed on silica, using 40% EtOAc in hexanes to elute. The product was dissolved in a solution of ethanol and aqueous 2.5 N sodium hydroxide and stirred for 3 hours at room temperature. The solution was concentrated in vacuo and water added. The mixture was extracted with ether; the aqueous layer was acidified to pH 4 with 1 N H3PO4 and extracted with EtOAc. The latter organic extract was washed with brine and dried over Na2Sθ4. To 100 mg (0.10 mmol) of the azide was added 1mL of 1M HCI(aqr.), 0.5 mL of dioxane, and 5 mg of 10% Pd-C The suspension was stirred under 1 atm. of H2 for 5 hours, then filtered and concentrated to a white solid. The product was purified via HPLC, eluting with a 0 to 70 CH3CN in 0.1% aqueous TFA gradient to give the title compound as its TFA salt. 1 H NMR (CD3OD, 300 MHz) δ 0.92 (t, J=7.0 Hz, 3H), 0.96 (t, rotamer), 1.23 (m, 2H), 1.41 (m, 2H), 3.06 (m, 4H), 3.39 (m, 2H), 3.69 (m, 2H), 3.84 (s, 3H), 3.94 (m, 3H), 4.18 (m, 2H), 5.05 (bd, J=10.7 Hz, 1 H), 5.98 (s, 2H), 6.84 (d, J=7.7 Hz, 1H), 6.93 (dd, J=1.8, 8.1 Hz, 1 H), 7.05 (m, 3H), 7.56 (m, 2H). MS (DCI/NH3) at m/e 498 (M+H) + . Anal calcd for C27H35N306-3.15 TFA: C, 46.68. H, 4.49. N, 4.90. Found: C, 46.61 ; H, 4.73; N, 4.79. Example 526 trans. frans-2-f4-Methoxyphenyn-4-f 1 .3-benzodioxol-5-yn-1-ffN- butyl-N-f3-aminopropynamino)carbonylmethyl ' [-pyrrolidine-3- carboxylic acid To and ice-cold solution of the compound of Example 523C (100 mg, 0.19 mmol) in 1 mL of dichloromethane was added 17mL of methanesulfonyl chloride, and 39 mL of triethylamine. The mixture was stirred for 20 min, then diluted with 1.5 mL of dichloromethane and extracted once with 5mL of water to which had been added 1 drop of 85% H3PO4, then 5% ammonium hydroxide (1 x 2.5 mL), and brine (1 x 2.5 L), dried over MgSθ4, filtered, and concentrated to an oil. To a solution of 81 mg (0.13 mmol) of the mesylate in 1mL of DMF was added 65 mg (10 mmol) of sodium azide. The mixture was stirred for 1 hour at 50 " C, then poured into 10 mL of water and extracted with diethyl ether (3 x 5 mL). The combined ether layers were back extracted with brine (1 x 5 mL), dried over MgSθ4, filtered, and concentrated to an oil. This was purified via silica gel chromatography, eluting with 60:40 hexanes: ethyl acetate to give 57 mg of a colorless oil. The product was dissolved in a solution of ethanol and aqueous 2.5 N sodium hydroxide and stirred for 3 hours at room temperature. The solution was concentrated in vacuo and water added. The mixture was extracted with ether; the aqueous layer was acidified to pH 4 with 1 N H3PO4 and extracted with EtOAc. The latter organic extract was washed with brine and dried over Na2Sθ4. To this azide was added 1mL of 1 M 0.5 mL of dioxane, and 5 mg of 10% Pd-C The suspension was stirred under 1 atm. of H2 for 5 hours, then filtered and concentrated to a white solid. The product was purified via HPLC, eluting with a 0 to 70 CH3CN in 0.1% aqueous TFA gradient to give the title compound as its TFA salt. 1 H NMR (D6-DMSO, 300 MHz) δ 0.85 (apparent q, J=6.8 Hz, 3H), 1.17 (m, 2H), 1.30 (m, 2H), 1.67 (m, 2H), 2.71 (m, 2H), 3.04 (m, 1 H), 3.21 (m, 3H), 3.45 (m, 1 H), 3.75 (m, 3H), 3.97 (s, 3H), 3.85-4.80 (broad m, 3H), 6.03 (m, 2H), 6.87 (dd, J=1.4, 8.1 Hz, 1 H), 6.92 (d, J=7.8 Hz, 1 H), 7.01 (m, 2H), 7.16 (m, 1 H), 7.55 (m, 2H), 7.72 ( , 2H), 7.85 (m, 1 H); MS (DCI/NH3) (M+H)+ at m/e 512. Anal calcd for C28H37N3θ6'3.0 TFA: C, 47.84. H, 4.72. N, 4.92. Found: C, 47.86; H, 4.75; N, 4.97. Example 527 trans. frans-2-f4-Methoxyphenyn-4-f 1 .3-benzodioxol-5-yn- 1 -ffN- butyl-N-f3-dimethylaminopropynamino carbonylmethyl1-pyrrolidine- 3-carboxylic acid Example 527A N-butyl-N-f3-bromopropynbromoacetamide To 1.50g (11.4 mmol) of N-butyl-N-(3-hydroxy)propyiamine was added 3 mL of 48% HBr(ag.), and 1.5 mL of cone. H2SO4. The reaction was stirred at reflux for 3 hours, then cooled to room temperature and stirred for 22 hours. The mixture was poured over 50 mL of ice, and the solution was treated with 50 mL of 2M NaOH(ag.)- The basic solution was extracted with ethyl acetate (3 x 25 mL), then the combined ethyl acetate layers were back extracted with brine (1 x 25 mL), dried, and filtered. To the ice cooled ethyl acetate solution was added 3mL of triethylamine, then 1.5 mL of bromoacetyl bromide as a solution in 3.5 mL of ethyl acetate. The reaction was stirred at 0 " C for 30 min, then extracted with 1 M HCI( a g.) (2 x 25 mL) saturated NaHCθ3(ag.) (1 25 mL) and brine (1 x 25 mL). The organic layer was dried over MgS04, filtered, and concentrated to an oil. This was purified via silica gel chromatography, eluting with 30% ethyl acetate in hexanes to give 1.47g of a colorless oil. Example 527B Ethyl trans. fraπs-2-f4-Methoxvρhenvn-4-f 1 .3-benzodioxol-5-yn-1 - IfN-butyl-N-(3-bromoproDvnamino arbonylmethvn-pyrrolidine-3- ςarbQxyiate According to the procedure of Example 523C, N-butyl-N-(3- o bromopropyl-bromoacetamide was coupled with ethyl 2-(4- Methoxyphenyl)-4-(1 ,3-benzodioxol-5-yl)-pyrrolidine-3-carboxylate. The crude product was chromatographed on silica, using 40% EtOAc in hexanes to elute. 5 Example 527C trans. frans-2-f4-Methoxyphenvn-4-f 1 .3-benzodioxol-5-yn-1 -r, (N- butyl-N-f 3-di meth l aminop ropy namino^carbony I methyll-py rrolidine- 3-carboxylic acid 0 To 400 mg (0.663 mmol) of the compound of Example 527B in 4 mL of absolute EtOH was added 1.2 mL of 2.0 M Me2NH in THF. The reaction was heated at 50 'C for 3h, then stirred at room temperature for 18 hours. The mixture was concentrated, then reconcentrated from CH3CN to remove most of the trimethylamine. The product was 5 purified via silica gel chromatography, eluting with 9:1 CH2CI2: MeOH over about 20 L of silica gel to give the ethyl ester. The product was dissolved in a solution of ethanol and aqueous 2.5 N sodium hydroxide and stirred for 3 hours at room temperature. The solution was concentrated in vacuo and water added. The mixture was extracted 0 with ether; the aqueous layer was acidified to pH 4 with 1N H3PO4, and the product was purified by preparative HPLC. 1 H NMR (CD3OD, 300 MHz) δ 0.92 (t, J=7.0 Hz, 3H), 1.22 (m, 2H), 1.39 (m, 2H), 1.90 (m, 2H), 2.87 (s, 6H), 3.07 (m, 4H), 3.24 (m, 1H), 3.43 (m, 1H), 3.62 (m, 1 H), 3.84 (s, 3H), 3.88 (m, 3H), 4.07 (m, 1H), 4.17 (m, 1H), 4.97 ( , 1H), 5.97 (s, 5 2H), 6.83 (d, J=8.1 Hz, 1 H), 6.93 (dd, J=1.7, 8.1 Hz, 1 H), 7.05 (m, 3H), 7.53 (m, 2H). MS (DCI/NH3) at m/e 540 (M+H) + . Anal calcd for C3θH4l N3θ6'2.85 TFA: C, 49.22. H, 5.06. N, 4.80. Found: C, 49.16; H, 5.11 ; N, 4.62. Example 528 trans, frans-2-f 4-Methoxyphenyl »-4-f 1 .3-benzodioxol-5-yn- 1 -rfN- butyl-N-f3-trimethylammoniopropynamino^carbonylmethyn- pyrrolidine-3-carboxylic acid Prepared according to the procedures of Example 527C, substituting aqueous Me3N for Me2NH. 1 H NMR (CD3OD, 300 MHz) δ 0.91 (m, 3H), 1.24 (m, 2H), 1.40 (m, 2H), 1.99 (m, 2H), 3.13 (s, 9H), 3.18 (s, rotamer), 3.20 (m, 3H), 3.38 (m, 4H), 3.72 (m, 1 H), 3.84 (s, 3H), 4.03 (m, 3H), 4.35 (m, 1 H), 5.19 (m, 1 H), 5.97 (s, 2H), 6.84 (d, J=8.1 Hz, 1 H), 6.96 (dd, J=1.7, 7.9 Hz, 1 H), 7.10 (m, 3H), 7.62 (m, 2H). MS (DCI/NH3) at m/e 554 (M+H) + . Anal calcd for C31 H44N3O6O.I H2θ « 1.65 TFA: C, 47.25. H, 4.96. N, 4.32. Found: C, 47.25; H, 4.74; N, 4.75. Example 529 trans. frans-2-f4-Methoxyphenyn-4-f 1 .3-benzodioxol-5-yn- 1 -rfN- butyl-N-f4-aminobutynamino)carbonylmethyl1-pyrrolidine-3- carboxylic acid Example 529A N-butyl-N-f4-hvdroxybutvn-amine A solution of 8.1 g (1 10 mmol) of n-butylamine and 8.6 g of butyrolactone in 50 ml toluene was allowed to reflux under nitrogen atmosphere for 50 hours. Volatile solvents were removed in vacuo. To a solution of 3.18 gm (20 mmol) of the resultant N-butyl -4- hydroxybutyramide in 50 ml of toluene were added 120 ml (120 mmol) DIBAL(25%W). The solution was heated with stirring at 70 * C for 18 hours. After cooling to 0'C, the reaction was quenched with methanol (1/3 amount of DIBAL solution was used) followed by addition of saturated solution of Rochelle's salt. The mixture was extracted twice with EtOAc; the organic extracts were washed with brine and dried over Na2Sθ4. Example 529B N-butyl-N-f4-hvdroxybutvn-chloroacetamide Pyridine (2 ml) was added to an ice cold solution of 0.58 gm (4 mmol) of N-butyl-N-(4-hydroxybutyJ)-amine in 10 ml of EtOAc. To this solution 0.769 gm (4.5 mmol) chloroacetic anhydride was added in small portions. The reaction mixture was allowed to stir for 5 hours at O'C, and then was allowed to warm to room temperature. o Bicarbonate was added, and the resultant mixture was extracted with EtOAc. The organic layer was washed with water and brine. The crude material was purified by column chromatography. Example 529C 5 Ethyl trans. frans-2-f4-Methoxyphenyn-4-( 1 .3-benzodioxol-5-yn-1 - f(N-butyl-N-f4-hydroxybutynamino carbonylmethyH-pyrrolidine-3- carboxylate According to the procedure of Example 523C, N-butyl-N-(4- 0 hydroxybutyl-chloroacetamide was coupled with ethyl 2-(4- Methoxyphenyl)-4-(1 ,3-benzodioxol-5-yl)-pyrrolidine-3-carboxylate. The crude product was chromatographed on silica gel. Example 529D 5 Ethyl trans. fraπs-2-(4-Methoxyphenyn-4-f 1 ,3-benzodioxol-5-yn-1 - f(N-butyl-N-(4-bromobutvnammo arbonytmethyl1-pyrrolidine-3- carboxylate To the solution of 0.180 gm (0.33 mmol) of the compound of 0 Example 529C in 2 ml DMF 0.086 gm (1 mmol) of lithium bromide and 0.120 ml (0.66 mmol) of PBr3 was added. The reaction mixture was allowed to stir at O'C for 2 hours and was slowly warmed to room temperature. Bicarbonate was added, and the resultant mixture was extracted with EtOAc. The organic layer was washed with water and 5 brine. The crude material was purified by column chromatography. Example 529E trans. frans-2-f4-Methoχyphenvn-4-f 1 .3-benzodioxol-5-yn-1 -rfN- butyl-N-f4-aminobutynamino)carbonylmethyl1-pyrrolidine-3- carboxylic acid To a solution of 0.135 gm (0.21 mmol) of the compound of Example 529D in 2 ml DMF was added 0.1 gm of sodium azide. Reaction was allowed to stir at room temperature for 18 hours under nitrogen atmosphere. After addition of water, the product was extracted into EtOAc. The crude product (117 mg) was dissolved in 10 ml ethanol under nitrogen atmosphere. To this 45 mgs of 10% Pd/C catalyst was added, the nitrogen from the reaction flask was evacuated and was flushed with hydrogen by placing a balloon filled with hydrogen. The reaction was allowed to stir for 4 hours under hydrogen atmosphere, and was worked up by filtering through a Celite pad. The product was dissolved in a solution of ethanol and aqueous 2.5 N sodium hydroxide and stirred for 8 hours at room temperature. The solution was concentrated in vacuo and water added. The mixture was extracted with ether; the aqueous layer was acidified to pH 4 with 1 N H3PO4, and the product was purified by preparative HPLC. 1 H NMR (CD3OD, 300 MHz) δ 0.90 (t, J=7 Hz, 3H), 1.10-1.65 (m, 6H), 2.85-2.95 (m, 2H), 3.00- 4.10 (m, 14H), 5.50 (d, J=3 Hz, 2H), 5.97 (s, 2H), 6.82 (d, J=8 Hz, 1 H), 6.91 (dd, J=7 Hz, 1 H), 7.00-7.06 (m, 3H), 7.45-7.55 (m, 2H). MS (DCI/NH3) at m/e 526 (M+H) + . Anal calc'd for C29H39N306-2.2 TFA: C, 51.75; H, 5.35; N, 5.41. Found: C, 51.75; H, 5.31 ; N, 5.30. Example 530 trans, frans-2-f 4-MethoxyphenylY4-f 1 .S-benzodioxol-δ-vn- l -ffN- butyl-N-f4-dimethylaminobutvnamino^carbonylmethyπ-pyrrolidine-3- carboxylic acid The title compound was prepared from the compound of Example 529D, employing the procedures of Example 527C 1 H NMR (CD3OD, 300 MHz) δ 0.90 (dt, J=7Hz, 3H), 1.1-1.75 (m, 8H), 2.75 (d, J=7 Hz, 6H), 3.0- 4.25 (m, 16H), 5.97 (s, 2H), 6.83 (d, J=8 Hz, 1 H), 6.93 (dd, J=8 Hz, 1 H), 7.02-7.08 (m, 3H), 7.49-7.56 (m, 2H). MS (DCI/NH3) at m/e 554 (M+H) + . Anal calc'd for C-3l H43N3θ6'2.1 TFA: C, 53.31 ; H, 5.73; N, 5.30. Found: C, 53.50; H, 5.38; N, 5.34. Example 531 trans. frans-2-f4-Methoxyphenyn-4-f 1 ,3-benzodioxol-5-yn-1 -rfN- butyl-N-f3-pyridvnaminθ )Carbonylmethyl1-pyrrolidine-3-carboxylic acid Example 531 A N-butyl-N-f3-pyridvn-amine To a solution of 941 mg (10 mmol) of 3-aminopyridine and 0.9 mL of butyraldehyde in 30 mL of CH3OH was added 10 mL of glacial acetic acid. The mixture was stirred at room temperature for 1 hour, then the reaction was cooled with an ice bath, and 650 mg (10.3 mmol) of sodium cyanoborohydride was added. The ice bath was removed, and the reaction was stirred for 4.5 hours at room temperature. The mixture was poured into 300 mL of 0.67M and extracted with ethyl acetate (3 x 50 L). The combined organic layers were back extracted with brine (1 x 50 mL), dried over MgS04, filtered, and concentrated to an oil. The product was isolated via silica gel chromatography, eluting with 3:1 ethyl acetate: hexanes to give 1.18g (79%) of a colorless solid. Example 531 B trans, trans-2-i 4- Methoxy phenylY4-f 1 .3-benzodioxol-5-vn-1 -ffN- butyl-N-f3-pyridvnamino carbonylmethyl1-pyrrolidine-3-carboxylic acid The compound of Example 531 A was reacted according to the procedures of Example 523, to give the title compound. 1 H NMR (Dβ- DMSO, 300 MHz) δ 0.80 (t, J=6.4 Hz, 3H), 1.15-1.99 (m, 4H), 2.59 (m, 1H), 3.05 (m, 2H), 3.26 (m, 2H), 3.49 (m, 2H), 3.56 (t, J=7.1 Hz, 2H), 3.73 (s, 3H), 6.00 (s, 2H), 6.80 (m, 3H), 6.85 (d, J=8.1 Hz, 1H), 6.98 (m, 2H), 7.04 (m, 1 H), 7.41 (dd, J=1 , 4.7 Hz, 8.1 H), 7.58 (m, 1 H), 8.36 (bs, 1 H), 8.54 (bs, 1H), 12.24 (bs, 1 H). MS (DCI/NH3) at m/e 532 (M+H) + . Anal calcd for C30H33N3O6O.I H3PO4: C, 66.55. H, 6.20. N, 7.76. Found: C, 66.59; H, 6.06; N, 7.60. Example 532 trans. frans-2-f4-Methoxyphenyn-4-f 1.3-benzodioxol-5-yl)-1 -ffN- butyl-N-(3-aminomethyl p henynamino ) carbonylmethyl -pyrrolidine-3- carboxylic acid Example 532A N-butyl-N-f3-hvdroxymethylPhenvn-amine To a solution of 3.69 g (30 mmol) of 3-amino benzyl alcohol in 20 ml DMSO was added 3.78 g (45 mmol) solid NaHC03 and 2.91 ml (27 mmol) 1-bromobutane. The reaction was allowed to stir at 50 * C for 18 hours (overnight). Reaction was worked up by adding 250 ml water and product was extracted in ethyl acetate. Water was added, and the resultant mixture was extracted with EtOAc. The organic layer was washed with water and brine. Example 532B N-butyl-N-f3-hvdroxymethylphenyl)-bromoacetamide To a solution of 3.42 g (19.2 mmol) of the compound of Example 532A in 20 ml toluene, was added 2.42 ml (30 mmol) pyridine. The mixture was cooled to O'C; 4.025 gm (20.0 mmol) of bromoacetyl bromide (diluted with 5 ml toluene) was added in a dropwise fashion. The reaction mixture was allowed to stir for 5 hours at O'C and then was allowed to warm to room temperature. Saturated potassium carbonate solution was added, and the mixture was stirred vigorously for 2 hours. The mixture was extracted with EtOAc; the organic layer was washed with 1 N H3PO4, water, and brine. Example 532C Ethyl trans. frans-2-f4-Methoχyphenvn-4-f 1 .3-benzodioxol-5-yn-1 - [fN-butyl-N-f3-chloromethylphenyl)amino^carbonylmethyη- pyrrolidine-3-carboxylate According to the procedure of Example 523C, N-butyl-N-(3- hydroxymethylphenyl)-bromoacetamide was coupled with ethyl 2-(4- Methoxyphenyl)-4-(1 ,3-benzodioxol-5-yl)-pyrrolidine-3-carboxylate. The crude product (129 mg) was dissolved in 0.5 ml of DMF and cooled to 0°C; 19 mg of LiCI was added, followed by 85 μl of thionyl chloride. The mixture was allowed to stir for 30 min; water was added, and the mixture was extracted with EtOAc. The organic extracts were washed with water and brine, and dried over Na2Sθ4- Example 532D trans. frans-2-f4-Methoxyphenyn-4-f 1 .3-benzodioxol-5-vn-1 -f(N- butyl-N-f3-aminomethylphenynamino^carbonylmethyl ' j-pyrrolidine-3- carboxylic acid The compound of Example 532C (182 mg) was dissolved in 1 mL of DMF. Two drops of water were added, followed by 126 mg (2.0 mmol, 6.5 eq) of sodium azide. The resultant solution was heated at 115 °C for 3 hours. Water was added, and the mixture was extracted with EtOAc. The organic extracts were washed with water and brine, and dried over a2S04. Example 532E trans, frans-2-f 4-Methoxyphenvn-4-f 1 .3-benzodioxol-5-vn-1 -[fN- butyl-N-f3-aminomethylphenylιamino)carbonylmethyll-pyrrolidine-3- carboxylic acid In a 50 ml round bottom flask 0.090 gm Tin (II) chloride was suspended in 1 ml acetonitrile. Triethylamine (0.2 mL) was added, followed by 0.19 ml of thiophenol ; the reaction mixture turned yellow. Reaction flask was cooled to O'C in ice bath; a solution of 0.185 gm of the compound of Example 532D in 2 ml acetonitrile was added. The mixture was allowed to stir for 30 min. Ether (10 ml) was added, followed by addition of 10 ml 2N HCl . The aqueous extract was basified with 4N NaOH and extracted with dichloromethane. The organic layer was washed with water and brine. The crude product was dissolved in a solution of ethanol and aqueous 2.5 N sodium hydroxide and stirred for 8 hours at room temperature. The solution was concentrated in vacuo and water added. The mixture was extracted with ether; the aqueous layer was acidified to pH 4 with 1 N H3PO4, and the product was purified by preparative HPLC. 1 H NMR (CD3OD, 300 MHz) δ 0.88 (t, J=7 Hz, 3H), 1.15-1.45 (m, 4H), 3.40-4.20 (m, 14H), 5.87 (s, 2H), 6.82 (d, J=8 Hz, 1 H), 6.88 (dd, J=8 Hz, 1 H), 6.87-7.20 (m, 5H), 7.40 (d, J=9 Hz, 2H), 7.56 (d, J=5 Hz, 2H). MS (DCI/NH3) at m/e 560 (M+H)Y Anal calcd for C32H37N3θ6'4.2 TFA: C, 46.72; H, 4.00; N, 4.05. Found: C, 46.66; H, 4.06; N, 4.00. Example 533 trans. frans-2-f4-Methoxyphenvn-4-f 1 .3-benzodioxol-5-vn-1 -rfN- butyl-N-f3-trimethylammoniomethylphenvnamino)carbonylmethyl ' }- pyrrolidine-3-carboxylic acid To a stirred solution of 0.128 gm of the compound of Example 532C in 0.5 ml methanol, 0.25 ml of an aqueous solution of trimethylamine was added. The mixture was allowed to stir at room temperature under nitrogen atmosphere for 4 hours. 1 N HCl was added; the aqueous was washed with ether to extract organic impurities. The aqueous layer was dried azeotropically with toluene, and the residue was dried under high vacuum. Yield 0.115 gm. 1 H NMR (300 MHz, D6- DMSO) δ 0.83 (t, J=7 Hz, 3H), 1.15-1.40 (m, 4H), 2.62 (s, 2H), 3.35 (s, 9H), 3.40-3.80 (m, 10H), 4.47 (s, 2H), 6.00 (s, J=3 Hz, 2H), 6.75-6.90 (m, 3H), 7.25-7.37 (m, 2H), 7.45-7.60 (m, 3H). MS (DCI/NH3) at m/e 602 (M+H) + . Example 534 t;.?fi.3ft.4S)-2-f3-Fluoro-4-methoxyphenvn-4-f 1 .3-benzodioxol-5-yn i - f2-fN-propyl-N-pentanesulfonylamino^ethvn-pyrrolidine-3-carboxylic acid Example 534A Ethyl f3-fluoro-4-methoxy benzoylacetate Sodium hydride (17g of a 60% suspension in mineral oil) is washed three times with toluene. The powder is suspended in 138 mL of toluene, and 35 mL of diethyl carbonate is added. The mixture is heated to 90 °C, and a solution of 25 g of 3-fluoro-4- methoxyacetophenone and 50 ml of diethyl carbonate in 50 ml of toluene was added portionwise. Heating is continued for 30 min, then the reaction is cooled to room temperature. A solution of 50 ml of concentrated HCl in 75 ml of ice water is added slowly, and the mixture is stirred. The mixture is extracted with toluene; the combined organic extracts are washed with brine and bicarbonate solutions. The product is dried over Na2Sθ4 and decolorized with charcoal to give 34.5 g (97%) of the title compound. Example 534B Ethyl 2-(3-Fluoro-4-methoxyphenyn-4-f 1 .3-benzodioxol-5-yn- pyrrolidine-3-carboxylate The compound of Example 534A (12.5 g) and 5-(nitrovinyl)-1 ,3- benzodioxole (13.1 g, 20% excess) were suspended in a mixture of 75 ml of THF and 13 ml of iPrOH. DBU (0.25 g) was added, and the mixture was stirred at room temperature for 30 min. An additional 0.1 g of DBU was added, and the solution was stirred for 1 hour. The solvents were removed in vacuo; toluene was added, along with brine containing 3 ml of concentrated HCl. The mixture was extracted twice with toluene; the organics were dried over MgS04. The residue was flashed on silica, using CH2CI2 to elute. Yield 75%. This material (17.4 g) is combined with 35 g of Raney Nickel (washed) in 250 mL of EtOAc. The mixture is shaken under 4 atm of hydrogen for 18 hours. The solution is concentrated in vacuo; the residue is chromatographed on silica, eluting with 4% EtOAc in CH2CI2. Yield 10.13 g = 66%. The product is combined with 26 ml of THF and 50 ml of EtOH; 2.18 g of NaBH3CN are added, along with a trace of bromcresol green as indicator. A solution of 1 :2 concentrated HCl/EtOH is added dropwise to maintain pH at green-yellow; after color persists, the reaction mixture is stirred for an additional 20 min. The solvents are removed in vacuo; the residue is stirred with mixture of toluene and KHCO3 solution. The organic phase is washed with water and brine, and dried over MgSθ4. The crude product is purified by flash chromatography on silica, eluting with 2:1 EtOAc/hexanes. Yield 5.92 g (58%) of a 2:1 mixture of trans-trans and cis-trans isomers. Example 534C Ethyl f;?fl.3fl.4SV2-f3-Fluoro-4-methoxyphenvn-4-f 1 .3-benzodioxol- 5-vH- pyrrol id ine-3-carboxylate To the racemic amino ester above (15.0 g, 38.8 mmol), dissolved in 75 ml methylene chloride and cooled in an ice bath, was added Boc anhydride (9.30 g, 42.7 mmol). After stirring 2 hours at room temperature, the solution was concentrated in vacuo ; the residue was dissolved in 50 ml ethanol and treated with a solution of 3.75 g sodium hyroxide in 19 ml water. The solution was warmed until all was soluble. After stirring for 2 hours at room temperature, the solution was concentrated and redissolved in 200 ml of water. This was extracted with 75 ml of diethyl ether. The ether layer was extracted with 40 ml of water. The combined aqueous phases were acidified with 7.5 g acetic acid; the mixture was stirred until a solid formed. The solid was filtered, washed with water and dissolved in methylene chloride. After drying with sodium sulfate, the solution was concentrated and the residue crystallized from 1 :1 etheπhexane to get 15.99 g of product, m.p. 200-203 (90% yield). The crude acid was suspended in 80 ml ethyl acetate and treated with 4.00 g (33.1 mmol) of (S)-(-)-a-methylbenzylamine. After heating to dissolve the acid, 80 ml of ether was added. Scratching with a glass rod caused the product to crystallize. The solids were filtered and washed with ether-ethyl acetate solution to give 8.22 g (81% yield based on 50% maximum recovery) of salt, m.p. 165-168°C After one recrystallization, chiral HPLC analysis, using a Regis Whelk-0 column, indicated >99.5 % e.e. The salt was dissolved in 500 ml of 36% HCl in ethanol; a white solid forms. The resultant suspension was heated for 16 hours at 52°C After concentrating in vacuo, the residue was combined with toluene and stirred with potassium bicarbonate in water for 30 minutes. The toluene was separated, dried (Na2S04) and concentrated. The residue was chromatographed on silica gel, eluting with 33% hexane-67% ethyl acetate to get 6.9 g (99%) of the resolved amino ester. Example 534D Ethyl (2 3ff.4S)-2-f3-Fluoro-4-methoxyphenvn-4-f 1 .3-benzodioxol- 5-yn i -f2-f N-propylamino)ethyn-pyrrolidine-3-carboxylate The compound of Example 534C was dissolved in 1 ,2- dibromoethane ( 10 mL per 1 g of starting material ); diisopropylethylamine (1 mL per 1 g of starting material ) and Nal ( 100 mg per 1 g of starting material) were added, and the mixture was stirred at 100°C for 1 hour. Toluene was added, and the mixture was washed with bicarbonate. The solvents were concentrated, and the resultant black residue was chromatographed on silica gel, eluting with 4:1 hexane-EtOAc to give the N-(2-bromoethyl)pyrrolidine (85- 92%). This compound was combined with n-propylamine (3.5 eq.) and Nal (10% by weight of bromide) in ethanol ( 5 mL per 1 g of bromide), and was heated at 80°C for 2 hours. Toluene was added, and the mixture was washed with bicarbonate, dried (Na2S04), and concentrated. More toluene was added, and removed in vacuo, to get rid of the primary amine. The residue was dissolved in heptane and filtered to remove a small amount of insoluble material. Evaporation of the solvent gave the desired product (86-93% yield), which was used for the next step without further purification. Example 534E 1-Pentanesulfonyl chloride 1-Pentanesulfonic acid, sodium salt (10 g, 57.5 mmol) was charged into a 250 ml round bottom flask (allow headroom). Thionyl chloride (20 mL) is added; gas evolves, and a while solid forms. The mixture is heated at 60 °C for 3 hours. The solvents are removed in vacuo; toluene is added and removed in vacuo to remove residue of SOCI2- The residue is partitioned between CH2CI2 and ice water; the organic layer is dried over Na2Sθ4 • The crude product is purified by distillation (bp 54-56 °C @ 0.5 mm Hg) to give a clear oil, 61% yield. Example 534F ^■?ff.3/?.4S)-2-f3-Fluoro-4-methoxyphenvn-4-f 1 .3-benzodioxol-5-yl)1 - f2-fN-propyl-N-pentaπesulfonylamino)ethyn-pyrrolidine-3-carboxylic acid The compound of Example 534D (200 mg, 0.43 mmol) was dissolved in 5 mL of CH3CN; 110 mg (2 eq) of N,N- diisopropylethylamine and 72.8 mg (1.2 eq) of 1 -pentanesulfonyl chloride were added sequentially, the resultant solution was allowed to stir at room temperature for 30 min. The solvent was evaporated under reduced pressure and the residue was dissolved in EtOAc. The solution was washed with saturated NaHC03 solution, 1N H3PO4, and brine, dried over Na2Sθ4 and evaporated to give a yellowish oil which was purified by flash chromatography on silica gel eluting with 40% EtOAc/hexane to give 220 mg of product (85%). This ester was dissolved in 5 mL of EtOH, to which was added NaOH (46 mg, 3 eq) solution in 2 mL of H2O. This mixture was stirred for 3 hours at room temperature. The solution was concentrated in vacuo using low (<40°C) heat. Water (10 mL) and ether (50 mL) were added; the ether layer was extracted with 5 mL of water. The combined aqueous mixture was back-extracted with ether and then neutralized with acetic acid. This solution was extracted twice with ether. The ether was dried (Na2S04) and concentrated in vacuo. EtOAc (1 mL) and ether (1 mL) were added to dissolve the product, and hexane was added dropwise to produce a white solid. The solid was collected and dried in vacuo to give 125 mg of the title compound. Example 534H f " .? 3f?.4S)-2-f3-Fluoro-4-methoxyphenvn-4-f 1 .3-benzodioxol-5-yni - (2-fN-propyl-N-pentanesulfonylamino^ethyn-pyrrolidine-3-carboxylic acid, hydrochloride salt The free amine is dissolved in iPrOH; a slight excess of HCl in iPrOH is added, and the solution is concentrated in vacuo. More IPA is added, and the solution is reconcentrated. The resultant sticky material is stirred with ether overnight to give a white powder, which is collected by filtration and dried overnight in vacuo at 60 °C Yield 95%. Example 535 The compounds in Table 3C may be prepared using methods presented in the above Examples. Table 3C. 16 17 18 3 44 45 103 104 105 133 134 135 148 149 150 163 164 165 178 179 180 193 194 195 208 209 210 Y " TJ N L --H ΓYΪ -OOH 217 218 219 223 224 225 238 239 240 268 269 270 283 284 285 295 296 297 310 311 312 325 326 327 340 341 342 355 356 357 371 385 386 387 427 428 429 436 437 438 439 440 441 448 449 450 482 483 496 497 498 515 523 524 525 529 530 531 538 539 540 550 551 552 559 560 561 565 566 567 628 629 718 719 720 730 731 732 769 770 771 793 794 795 829 830 831 841 842 843 853 854 855 877 878 879 919 920 921 949 950 951 994 995 996 - 552 1000 1001 1002 1015 1016 1017 1030 1031 1032 1060 1061 1062 1075 1076 1077 1105 1106 1107 1120 1121 1122 1135 1136 1137 1147 1148 1149 1150 1151 1152 1198 1199 1200 1210 1211 1212 1213 1214 1215 1237 1238 1239 1252 1253 1254 1282 1283 1284 1297 1298 1299 1327 1328 1329 1372 1373 1374 1387 1388 1389 1399 1400 1401 1414 1415 1416 1486 1487 1488 SUBSTTTUTE SHEET (RULE 26) SUBSTTTUTE SHEET (RULE 26) SUBSTTTUTE SHEET (RULE 26) - 60S As an indication that the compounds described herein act through binding to endotheiin receptors, the compounds have been evaluated for their ability to displace endotheiin from its receptor. 5 Binding Assay EIA Receptor Preparation of membranes from MMQ cells: MMQ [MacLeod/MacQueen/Login cell line (prolactin secreting rat pituitary cells)] cells from 150 mL culture flasks were collected by ι o centrifugation (1000xg for 10 min) and then homogenized in 25 L of 10 mM Hepes (pH 7.4) containing 0.25 M. sucrose and protease inhibitors [3 mM EDTA , 0.1 mM PMSF, and 5 μg/mL Pepstatin A] by a micro ultrasonic cell disruptor (Kontes). The mixture was centrifuged at 1000xg for 10 min. The supernatant was collected and centrifuged at 15 60,000xg for 60 min. The precipitate was resuspended in 20 mM Tris, pH 7.4 containing the above protease inhibitors and centrifuged again. The final pellet was resuspended in 20 mM Tris, pH 7.4 containing protease inhibitors and stored at -80°C until used. Protein content was determined by the Bio-Rad dye-binding protein assay. 0 [1 25 I1ET-1 binding to membranes: Binding assays were performed in 96-well microtiter plates pretreated with 0.1% BSA. Membranes prepared from cells were diluted -100 fold in Buffer B (20 mM. Tris, 100 mM. NaCI, 10 mM . MgCl2, pH 7.4, with 0.2% BSA, 0.1 mM. PMSF, 5 μg/mL Pepstatin A, 0.025% bacitracin, 5 and 3 mM EDTA) to a final concentration of 0.2 mg/mL of protein. In competition studies, membranes (0.02 mg) were incubated with 0.1 nM_ of [ 1 25 I]ET-1 in Buffer B (final volume: 0.2 mL) in the presence of increasing concentrations of unlabeled ET-1 or a test compound for 4 hours at 25 °C. After incubation, unbound ligands were separated from 0 bound ligands by a vacuum filtration method using glass-fiber filter strips in PHD cell harvesters (Cambridge Technology, Inc., MA), followed by washing the filter strips with saline (1 mL) for three times. Nonspecific binding was determined in the presence of 1 μM. ET-1. The data are shown in Table 4. The per cent inhibition at a concentration of 5 1 mM. is shown. The data show that the compounds of the invention bind to the endotheiin receptor. Exampie E As further demonstration of the efficacy of the described compounds as functional antagonists of endotheiin, the ability of the described compounds to inhibit ET-1 -induced phosphatidylinositol hydrolysis was measured. Determination of Phosphatidylinositol (P\) Hydrolysis MMQ cells (0.4 x 10 6 cells/mL) were labeled with 10 μCi/mL of [ 3 H]myo-inositol in RPMI for 16 hours. The cells were washed with ι o PBS, then incubated with Buffer A containing protease inhibitors and 10 mM LiCI for 60 minutes. The cells were then incubated with test compounds for 5 minutes, and then challenged with 1 nM ET-1. ET-1 challenge was terminated by the addition of 1.5 mL of 1 :2 (v/v) chloroform-methanol. Total inositol phosphates were extracted after 15 adding chloroform and water to give final proportions of 1 :1 :0.9 (v/v/v) chloroform-methanol-water as described by Berridge (Biochem. J. 206 587-595 (1982)). The upper aqueous phase (1 mL) was retained and a small portion (100 μL) was counted. The rest of the aqueous sample was analyzed by batch chromatography using anion-exchange resin AG1- 0 X8 (Bio-Rad). The IC50 is the concentration of test compound required to inhibit the ET-induced increase in PI turnover by 50%. The results of the above study clearly indicate that the compounds act as functional ET antagonists. 25 Table 5 Phosphatidylinositol Hydrolysis Table 6 ETA/ETB Selectivity MMQ cells, porcine cerebellar tissues (known to contain ETβ receptors) and Chinese hamster ovary cells (CHO) permanently ι o transfected with the human ETA or ETB receptor were homogenized in 25 ml of 10 mM Hepes (pH 7.4) containing 0.25 M sucrose and a protease inhibitor [50 mM EDTA , 0.1 mM PMSF, 5 μg/ml Pepstatin A, and 0.025% Bacitracin] using a micro ultrasonic cell disruptor. The mixture was centrifuged at 1000xg for 10 min. The supernatant was collected and s centrifuged at 60,000xg for 60 min. The precipitate was resuspended in 20 mM Tris, pH 7.4 containing protease inhibitor and centrifuged again. The final membrane pellet was resuspended in 20 mM Tris, pH 7.4 containing protease inhibitors and stored at -80 °C until used. Protein content was determined by the Bio-Rad dye-binding protein assay. Binding assays were performed in 96-well microtiter plates pretreated with 0.1% BSA. Membranes prepared from cells were diluted 5 -100 fold in Buffer B (20 mM. Tris, 100 mM NaCI, 10 mM MgCl2, pH 7.4, with 0.2% BSA, 0.1 mM PMSF, 5 μg/mL Pepstatin A, 0.025% bacitracin, and 50 mM EDTA) to a final concentration of 0.2 mg/mL of protein. In competition binding studies, membranes (0.02 mg) were incubated with 0.1 nM of [125I]ET-1 (for ETA assay in MMQ or CHO cells transfected ι o with human ETA receptor) or [125l]ET-3 (for ETB assay in porcine cerebellum or CHO cells transfected with human ETβ receptor) in Buffer B (final volume: 0.2 mL) in the presence of increasing concentrations of the test compound for 3 hours at 25 °C. After incubation, unbound ligands were separated from bound ligands by a vacuum filtration 15 method using glass-fiber filter strips in PHD cell harvesters (Cambridge Technology, Inc., MA), washing the filter strips three times with saline (1 mL). Nonspecific binding was determined in the presence of 1 μM ET-1. IC50 values are calculated using an average of at least two separate determinations. The data shows the selectivity of the 0 compounds of the invention in binding to the endotheiin receptors. Table 6 EXAMPLE mET-A mET-A pET-B Selectivity hET-A hET-B Selectivity NO. (%l @ IC50 IC50 (mA/pB IC50 IC50 (hA/hB 1 μM ) ( n M ) ( n M ) ratio) ( n M ) ( n M ) ratio) 502 95.7 3.0 71,000 23,000 503 97.0 1.4 50,000 35,000 0.92 52,000 56,000 504 97.1 3.1 >100,000 >32,000 4.6 >100,000 >21,000 505 95.8 2.0 60,000 30,000 5.7 68,000 12,000 506 99.7 3.2 >100,000 >31,000 3.0 61,000 20,000 507 99.3 3.0 > 100,000 >33,000 1 .63 > 1 00,000 >60 ,000 508 97.6 1 .9 45 ,000 23,000 2.1 51 ,000 24 ,000 509 100 0.56 30,000 53,000 0.51 23,000 45,000 510 100 0.50 35,000 68,000 1.0 11,000 11,000 511 99.2 0.81 N.D. 0.60 15,000 25,000 512 98.9 0.42 >80,000 >190,000 0.58 60,000 >102,000 513 98.0 0.30 8,800 29,000 0.36 14,000 37,000 514 100 1.0 26,000 26,000 0.36 9,800 29,000 515 99.1 1.6 >62,000 >37,000 6.7 >100,000 >15,000 516 99.7 0.71 29,000 40,000 1.8 37,000 21,000 517 94.1 1.0 30,000 30,000 0.43 12.000 29,000 518 96.3 1.3 85,000 63,000 0.31 38.000 124,000 519 99.1 0.38 14,000 36,000 0.23 19,000 83,000 520 97.4 0.20 28,000 130,000 521 100 0.67 37,000 54,000 523 99.0 0.42 360 880 0.33 290 880 524 99.2 0.79 1,700 2,100 0.82 890 1,100 525 100 8.2 560 70 526 100 42 - - - - - - 17 7,400 440 527 96.6 7.9 10,000 1,300 528 98.3 11 43,000 3,800 529 98.1 3.6 6,300 1,700 531 99.8 1.2 - - - - - - 0.71 870 1,200 532 100 5.1 3,200 630 533 97.9 76 7,900 100 40 22,000 560 534 0.12 0.36 3.0 0.08 0.28 3.5 Determination of Plasma Protein Binding A stock solution of the test compound in 50% ethanol (2 mg/mL) 5 was diluted 10X into PBS. A 0.4 mL sample of this secondary stock solution was added to 3.6 mL of fresh plasma, and incubated at room temperature for 1 hour. A 1 mL sample of this incubation mixture was transferred to a Centrifree ultrafiltration tube. The sample was centrifuged in a fixed-bucket rotor for approximately 2 min and the ι o filtrate was discarded. The sample was centrifuged for another 15-30 min. A 100 μL sample of the ultrafiltratewas transfered to a micro HPLC sample vial containing 150 ML of HPLC mobile phase and mixed thoroughly. A 50 μL sample was injected and the concentration of drug in the ultrafiltrate was determined by HPLC analysis compared against 15 a standard sample prepared identically in the absence of plasma. Ultrafiltrate concentrations are calculated from a calibration curve. Protein binding is calculated according to the equation: %PB = [1-(Cu/Ci)] * 100% 20 where Cu is the ultrafiltrate concentration and Ci is the initial plasma concentration. Data; Example #43 > 99.5 % Example #532 96.8% Example #533 82.6% The ability of the compounds of the invention to lower blood pressure can be demonstrated according to the methods described in Matsumura, et al., Eur. J. Pharmacol. 185 103 (1990) and Takata, et al., Clin. Exp. Pharmacol. Physiol. !£. 131 (1983). The ability of the compounds of the invention to treat congestive heart failure can be demonstrated according to the method described in Margulies, et al., Circulation £2. 2226 (1990). The ability of the compounds of the invention to treat myocardial ischemia can be demonstrated according to the method described in Watanabe, et al., Nature £44 1 14 (1990). The ability of the compounds of the invention to treat coronary angina can be demonstrated according to the method described in Heistad, et al., Circ. Res. £4. 711 (1984). The ability of the compounds of the invention to treat cerebral vasospasm can be demonstrated according to the methods described in Nakagomi, et al., J. Neurosurg. ££ 915 (1987) or Matsumura, et al., Life Sci. 42. 841 -848 (1991 ). The ability of the compounds of the invention to treat cerebral ischemia can be demonstrated according to the method described in Hara et al., European. J. Pharmacol. 1_9_7_: 75-82, (1991 ). The ability of the compounds of the invention to treat acute renal failure can be demonstrated according to the method described in Kon, et al., J. Clin. Invest. £1 1762 (1989). The ability of the compounds of the invention to treat chronic renal failure can be demonstrated according to the method described in Benigni, et al., Kidney Int. 44_ 440-444 (1993). The ability of the compounds of the invention to treat gastric 5 ulceration can be demonstrated according to the method described in Wallace, et al., Am. J. Physiol. 2££ G661 (1989). The ability of the compounds of the invention to treat cyclosporin-induced nephrotoxicity can be demonstrated according to the method described in Kon, et al., Kidney Int. £Z 1487 (1990). ι o The ability of the compounds of the invention to treat endotoxin- induced toxicity (shock) can be demonstrated according to the method described in Takahashi, et al., Clinical Sci. ZS. 619 (1990). The ability of the compounds of the invention to treat asthma can be demonstrated according to the method described in Potvin and i s Varma, Can. J. Physiol. and Pharmacol. £7 1213 (1989). The ability of the compounds of the invention to treat transplant- induced atherosclerosis can be demonstrated according to the method described in Foegh, et al., Atherosclerosis 7_£ 229-236 (1989). The ability of the compounds of the invention to treat 20 atherosclerosis can be demonstrated according to the methods described in Bobik, et al., Am. J. Physiol. 258 C408 (1990) and Chobanian, et al., Hypertension i£ 327 (1990). The ability of the compounds of the invention to treat LPL-related lipoprotein disorders can be demonstrated according to the method 25 described in lshida, et al., Biochem. Pharmacol. 4 1431-1436 (1992). The ability of the compounds of the invention to treat proliferative diseases can be demonstrated according to the methods described in Bunchman ET and CA Brookshire, Transplantation Proceed. 21 967-968 (1991); Yamagishi, et al., Biochem. Biophys. Res. Comm. 19J. 30 840-846 (1993); and Shichiri, et al., J. Clin. Invest. £Z 1867-1871 (1991). Proliferative diseases include smooth muscle proliferation, systemic sclerosis, cirrhosis of the liver, adult respiratory distress syndrome, idiopathic cardiomyopathy, lupus erythematosus, diabetic retinopathy or other retinopathies, psoriasis, scleroderma, prostatic 35 hyperplasia, cardiac hyperplasia, restenosis following arterial injury or other pathologic stenosis of blood vessels. The ability of the compounds of the invention to treat acute or chronic pulmonary hypertension can be demonstrated according to the method described in Bonvallet et al., Am. J. Physiol. 266 H1327 (1994). Pulmonary hypertension can be associated with congestive heart failure, mitral valve stenosis, emphysema, lung fibrosis, chronic obstructive pulmonary disease (COPD), acute repiratory distress syndrome (ARDS), altitude sickness, chemical exposure, or may be idiopathic. The ability of the compounds of the invention to treat plaletet aggregation, and thrombosis, can be demonstrated according to the method described in McMurdo et al. Eu. J. Pharmacol. 259 51 (1994). The ability of the compounds of the invention to treat cancers can be demonstrated according to the method described in Shichiri, et al., J. Clin. Invest. £7 1867 (1991). The ability of the compounds of the invention to treat IL-2 (and other cytokine) mediated cardiotoxicity and vascular permeability disorders can be demonstrated according to the method described in Klemm et al., Proc. Nat. Acad. Sci. £2 2691 (1995). The ability of the compounds of the invention to treat nociception can be demonstrated according to the method described in Yamamoto et al., J. Pharmacol. Exp. Therap. £71 156 (1994). The ability of the compounds of the invention to treat colitis can be demonstrated according to the method described in Hogaboam et al (EUR. J. Pharmacol. 1996, £££, 261-269). The ability of the compounds of the invention to treat ischemia- repurfusion injury in kidney transplantation can be demonstrated according to the method described in Aktan et al (Transplant Int 1996, £., 201-207). The ability of the compounds of the invention to treat angina, pulmonary hypertension, raynaud's disease, and migraine can be demonstrated according to the method described in Ferro and Webb (Drugs 1996, £1,12-27). The compounds of the present invention can be used in the form of salts derived from inorganic or organic acids. These salts include but are not limited to the following: acetate, adipate, alginate, citrate, aspartate, benzoate, benzenesulfonate, bisulfate, butyrate, camphorate, camphorsulfonate, digluconate, cyclopentanepropionate, dodecylsulfate, ethanesulfonate, glucoheptanoate, glycerophosphate, hemisulfate, heptanoate, hexanoate, fumarate, hydrochloride, hydrobromide, hydroiodide, 2-hydroxy-ethanesulfonate, lactate, maleate, 5 methanesulfonate, nicotinate, 2-naphthalenesulfonate, oxalate, pamoate, pectinate, persulfate, 3-phenylpropionate, picrate, pivalate, propionate, succinate, tartrate, thiocyanate, p-toluenesulfonate and undecanoate. Also, the basic nitrogen-containing groups can be quaternized with such agents as Ioweralkyl halides, such as methyl, ι o ethyl, propyl, and butyl chloride, bromides, and iodides; dialkyi sulfates like dimethyl, diethyl, dibutyl, and diamyl sulfates, long chain halides such as decyl, lauryl, myristyl and stearyl chlorides, bromides and iodides, aralkyl halides like benzyl and phenethyl bromides, and others. Water or oil-soluble or dispersible products are thereby obtained. 15 Examples of acids which may be employed to form pharmaceutically acceptable acid addition salts include such inorganic acids as hydrochloric acid, sulphuric acid and phosphoric acid and such organic acids as oxalic acid, maleic acid, succinic acid and citric acid. 0 Basic addition salts can be prepared in situ during the final isolation and purification of the compounds of formula (I), or separately by reacting the carboxylic acid function with a suitable base such as the hydroxide, carbonate or bicarbonate of a pharmaceutically acceptable metal cation or with ammonia, or an organic primary, 25 secondary or tertiary amine. Such pharmaceutically acceptable salts include, but are not limited to, cations based on the alkali and alkaline earth metals, such as sodium, lithium, potassium, calcium, magnesium, aluminum salts and the like, as well as nontoxic ammonium, quaternary ammonium, and amine cations, including, but not limited to ammonium, 30 tetramethylammonium, tetraethylammonium, methylamine, dimethylamine, trimethylamine, triethylamine, ethylamine, and the like. Other representative organic amines useful for the formation of base addition salts include diethylamine, ethylenediamine, ethanolamine, diethanolamine, piperazine and the like. 35 The compounds of the invention are useful for antagonizing endotheiin in a human or other mammal. In addition, the compounds of the present invention are useful (in a human or other mammal) for the treatment of hypertension, acute or chronic pulmonary hypertension, Raynaud's disease, congestive heart failure, myocardial ischemia, reperfusion injury, coronary angina, cerebral ischemia, cerebral 5 vasospasm, chronic or acute renal failure, non-steroidal antiinflammatory drug induced gastric ulceration, cyclosporin induced nephrotoxicity, endotoxin-induced toxicity, asthma, fibrotic or proliferative diseases, including smooth muscle proliferation, systemic sclerosis, cirrhosis of the liver, adult respiratory distress syndrome, ι o idiopathic cardiomyopathy, lupus erythematosus, diabetic retinopathy or other retinopathies, psoriasis, scleroderma, prostatic hyperplasia, cardiac hyperplasia, restenosis following arterial injury or other pathologic stenosis of blood vessels, LPL-related lipoprotein disorders, transplantation-induced atherosclerosis or atherosclerosis in general, 15 platelet aggregation, thrombosis, cancers, prostate cancer, IL-2 and other cytokine mediated cardiotoxicity and permeability disorders, and nociception, especially treatment of bone pain associated with bone cancer. Total daily dose administered to a host in single or divided doses 20 may be in amounts, for example, from 0.001 to 1000 mg/kg body weight daily and more usually 0.1 to 100 mg/kg for oral administration or 0.01 to 10 mg/kg for parenteral administration. Dosage unit compositions may contain such amounts of submultiples thereof to make up the daily dose. 25 The amount of active ingredient that may be combined with the carrier materials to produce a single dosage form will vary depending upon the host treated and the particular mode of administration. It will be understood, however, that the specific dose level for any particular patient will depend upon a variety of factors including so the activity of the specific compound employed, the age, body weight, general health, sex, diet, time of administration, route of administration, rate of excretion, drug combination, and the severity of the particular disease undergoing therapy. The compounds of the present invention may be administered 35 orally, parenterally, sublingually, by inhalation spray, rectally, or topically in dosage unit formulations containing conventional nontoxic pharmaceutically acceptable carriers, adjuvants, and vehicles as desired. Topical administration may also involve the use of transdermal administration such as transdermal patches or iontophoresis devices. The term parenteral as used herein includes 5 subcutaneous injections, intravenous, intramuscular, intrasternal injection, or infusion techniques. Injectable preparations, for example, sterile injectable aqueous or oleagenous suspensions may be formulated according to the known art using suitable dispersing or wetting agents and suspending agents. to The sterile injectable preparation may also be a sterile injectable solution or suspension in a nontoxic parenterally acceptable diluent or solvent, for example, as a solution in 1 ,3-propanediol. Among the acceptable vehicles and solvents that may be employed are water, Ringer's solution, and isotonic sodium chloride solution. In addition, i s sterile, fixed oils are conventionally employed as a solvent or suspending medium. For this purpose any bland fixed oil may be employed including synthetic mono- or diglycerides. In addition, fatty acids such as oleic acid find use in the preparation of injectables. Suppositories for rectal administration of the drug can be 20 prepared by mixing the drug with a suitable nonirritating excipient such as cocoa butter and polyethylene glycols which are solid at ordinary temperatures but liquid at the rectal temperature and will therefore melt in the rectum and release the drug. Solid dosage forms for oral administration may include capsules, 25 tablets, pills, powders, and granules. In such solid dosage forms, the active compound may be admixed with at least one inert diluent such as sucrose lactose or starch. Such dosage forms may also comprise, as is normal practice, additional substances other than inert diluents, e.g., lubricating agents such as magnesium stearate. In the case of capsules, 30 tablets, and pills, the dosage forms may also comprise buffering agents. Tablets and pills can additionally be prepared with enteric coatings. Liquid dosage forms for oral administration may include pharmaceutically acceptable emulsions, solutions, suspensions, syrups, and elixirs containing inert diluents commonly used in the art, such as 35 water. Such compositions may also comprise adjuvants, such as wetting agents, emulsifying and suspending agents, and sweetening, flavoring, and perfuming agents. The compounds of the present invention can also be administered in the form of liposomes. As is known in the art, liposomes are 5 generally derived from phospholipids or other lipid substances. Liposomes are formed by mono- or multi-lamellar hydrated liquid crystals that are dispersed in an aqueous medium. Any non-toxic, physiologically aceptable and metabolizable lipid capable of forming liposomes can be used. The present compositions in liposome form can ι o contain, in addition to a compound of the present invention, stabilizers, preservatives, excipients, and the like. The preferred lipids are the phospholipids and phosphatidyl cholines (lecithins), both natural and synthetic. Methods to form liposomes are known in the art. See, for 15 example, Prescott, Ed., Methods in Cell Biology. Volume XIV, Academic Press, New York, N.Y. (1976), p. 33 et seq. A representative solid dosage form, for example, a tablet or a capsule, comprises: Compound of the invention: 35% w/w 20 Starch, Pregelatinized, NF 50% w/w Microcrystalline Cellulose, NF 10% w/w Talc, Powder, USP 5% w/w While the compounds of the invention can be administered as the sole active pharmaceutical agent, they can also be used in combination 25 with one or more cardiovascular agents independently selected from diuretics, adrenergic blocking agents, vasodilators, calcium channel blockers, renin inhibitors, angiotensin converting enzyme (ACE) inhibitors, angiotensin II antagonists, potassium channel activators and other cardiovascular agents. 30 Representative diuretics include hydrochlorothiazide, chlorothiazide, acetazolamide, amiloride, bumetanide, benzthiazide, ethacrynic acid, furosemide, indacrinone, metolazone, spironolactone, triamterene, chlorthalidone and the like or a pharmaceutically acceptable salt thereof. 35 Representative adrenergic blocking agents include phentolamine, phenoxybenzamine, prazosin, terazosin, tolazine, atenolol, metoprolol, nadolol, propranolol, timolol, carteolol and the like or a pharmaceutically acceptable salt thereof. Representative vasodilators include hydralazine, minoxidil, diazoxide, nitroprusside and the like or a pharmaceutically acceptable 5 salt thereof. Representative calcium channel blockers include amrinone, bencyclane, diltiazem, fendiline, flunarizine, nicardipine, nimodipine, perhexilene, verapamil, gallopamil, nifedipine and the like or a pharmaceutically acceptable salt thereof. ι o Representative renin inhibitors include enalkiren, zankiren, RO 42-5892, PD-134672 and the like or a pharmaceutically acceptable salt thereof. Representative angiotensin II antagonists include DUP 753, A-81988 and the like. 15 Representative ACE inhibitors include captopril, enalapril, lisinopril and the like or a pharmaceutically acceptable salt thereof. Representative potassium channel activators include pinacidil and the like or a pharmaceutically acceptable salt thereof. Other representative cardiovascular agents include sympatholytic 0 agents such as methyldopa, clonidine, guanabenz, reserpine and the like or a pharmaceutically acceptable salt thereof. The compounds of the invention and the cardiovascular agent can be administered at the recommended maximum clinical dosage or at lower doses. Dosage levels of the active compounds in the 25 compositions of the invention may be varied so as to obtain a desired therapeutic response depending on the route of administration, severity of the disease and the response of the patient. The combination can be administered as separate compositions or as a single dosage form containing both agents. 30 When administered as a combination, the therapeutic agents can be formulated as separate compositions which are given at the same time or different times, or the therapeutic agents can be given as a single composition. The foregoing is merely illustrative of the invention and is not intended to limit the invention to the disclosed compounds, processes, compositions and methods. Variations and changes which are obvious to one skilled in the art are intended to be within the scope and nature of the invention which are defined in the appended claims.

Claims: CLAIMS What is claimed is: 1. A compound of the formula: wherein Z is -C(R18)(R19)- or -C(O)- wherein R-| 8 and R-j g are independently selected from hydrogen and Ioweralkyl; n is 0 or 1 ; R is -(CH2)m-W wherein m is an integer from 0 to 6 and W is (a) -C(0)2-G wherein G is hydrogen or a carboxy protecting group, (b) -PO3H2, (c) -P(0)(OH)E wherein E is hydrogen, Ioweralkyl or arylalkyi, (d) -CN, (e) -C(0)NHR17 wherein R17 is Ioweralkyl, (f) alkylaminocarbonyl, (g) dialkylaminocarbonyl, (h) tetrazolyl, (i) hydroxy, (j) alkoxy, (k) sulfonamido, (I) -C(0)NHS(0)2 16 wherein R16 is Ioweralkyl, haloalkyi, aryl or dialkylamino, (m) -S(0)2NHC(0)Ri 6 wherein R-j g is defined as above, Xf (r) R i is selected from Ioweralkyl, alkenyl, haloalkyi, haloalkoxyalkyi, cycloalkylalkyl, arylalkyi, aryloxyalkyl, arylalkoxyalkyi, (N-alkanoyl-N- alkyl)aminoalkyl, alkylsulfonylamidoalkyl, and (heterocyclic)alkyl; R2 is selected from the group consisting of hydrogen, Ioweralkyl, alkenyl, alkynyl, alkoxyalkyi, alkoxycarbonylalkyl, hydroxyalkyi, haloalkyi, haloalkoxyalkyi, alkoxyalkoxyalkyl, thioalkoxyalkoxyalkyi, (N- alkanoyl-N-alkyl)aminoalkyl, alkylsulfonylamidoalkyl, cycloalkyi, cycloalkylalkyl, aminocarbonylalkyl, alkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, aminocarbonylalkenyl, alkylaminocarbonylalkenyl, dialkylaminocarbonylalkenyl, hydroxyalkenyl, aryl, arylalkyi, aryloxyalkyl, arylalkoxyalkyi, heterocyclic, (heterocyclic)alkyl and (R aa )(Rbb) N " R cc" wherein R aa is aryl or arylalkyi, R^b is hydrogen or alkanoyl and R cc is alkylene, with the proviso that one or both of R- j and R2 is other than hydrogen; R3 is (a) R4-C(0)-R5-. R4-R5a". R6-S(0)2-R7- or R26-S(0)-R27- wherein R5 is (i) a covalent bond, (ii) alkylene, (iii) alkenylene, (iv) -N(R2θ)-R8- or -R8a" N ( R 2θ)' R 8~ wh e r e' n R 8 and Rg a are independently selected from the group consisting of alkylene and alkenylene and R20 is hydrogen, Ioweralkyl, alkenyl, haloalkyi, alkoxyalkyi, haloalkoxyalkyi, cylcoalkyl or cycloalkylalkyl or (v) -O-R9- or -Rg a -0-Rg- wherein Rg and Rg a are independently selected from alkylene; R δa is (i) alkylene or (ii) alkenylene; R7 is (i) a covalent bond, (ii) alkylene, (iii) alkenylene or (iv) -N(R21 )-R10- or -R-| 0a" N ( R 2l )- R 10- wherein R10 and R-j øa are independently selected from the group consisting of alkylene and alkenylene and R21 is hydrogen, Ioweralkyl, alkenyl, haloalkyi, alkoxyalkyi, haloalkoxyalkyi, aryl or arylalkyi; R4 and Re are independently selected from the group consisting of (i) (R1 1 )(R12)N- wherein Rn and R12 are independently selected from ( 1 ) hydrogen, (2 ) Iowe ral kyl , (3) haloalkyi, 75 (4) alkoxyalkyi, (5) haloalkoxyalkyi, (6) alkenyl, (7) alkynyl, (8) cycloalkyi, 80 (9) cycloalkylalkyl, (10) aryl, (11) heterocyclic, (12) arylalkyi, and (13) (heterocyclic)alkyl, 85 (14) hydroxyalkyi, (15) alkoxy, (16) aminoaikyl, and (17) trialkylaminoalkyl (ii) Ioweralkyl, 90 (iii) alkenyl, (iv) alkynyl, (v) cycloalkyi, (vi) cycloalkylalkyl, (vii) aryl, 95 (viii) arylalkyi, (ix) heterocyclic, (x) (heterocyclic)alkyl, (xi) alkoxyalkyi, (xii) hydroxyalkyi, 100 (xiϋ) haloalkyi, (xiv) haloalkenyl, (xv) haloalkoxyalkyi, (xvi) haloalkoxy, (xvii) alkoxyhaloalkyl, 105 (xviii) alkylaminoalkyl, (xix) diaikylaminoalkyl, (xx) alkoxy, and wherein z is 0-5 and Ry a is alkylene; R26 is (i) Ioweralkyl, (ii) haloalkyi, (iii) alkenyl, (iv) alkynyl, (v) cycloalkyi, (vi) cycloalkylalkyl, (vii) aryl, (viii) arylalkyi, (ix) 115 heterocyclic, (x) (heterocyclic)alkyl, (xi) alkoxyalkyi or (xii) alkoxy- substituted haloalkyi; and R27 is alkylene or alkenylene; (b)R22-0-C(0)-R23- wherein R22 is a carboxy protecting 120 group or heterocyclic and R23 is (i) a covalent bond, (ii) alkylene, (iii) alkenylene or (iv) -N(R24)-R25- wherein R25 is alkylene and R24 is hydrogen or 125 Ioweralkyl , (c) Ioweralkyl , (d) alkenyl, (e) alkynyl, (f ) cycloalkyi, 130 (g) cycloalkylalkyl, (h) aryl, (i ) arylalkyi, (j ) aryloxyalkyl, (k) heterocyclic, 135 ( I ) (heterocyclic)alkyl, (m) alkoxyalkyi, (n) alkoxyalkoxyalkyl, o r (0) R13-C(0)-CH(R14)- wherein R13 is amino, alkylamino or dialkylamino and R14 is aryl or 140 R -| 5-C(0)- wherein R15 is amino, alkylamino or dialkylamino; or a pharmaceutically acceptable salt thereof. 2. The compound according to Claim 1 wherein n is 0 and Z is ■ CH2-. 145 3. The compound according to Claim 1 wherein n is 1 and Z is -CH2-. 4. The compound according to Claim 1 wherein n is 0, Z is 150 -CH2-, and R3 is R4-C(0)-Rs- , Rg-S02-R7- or R26-S(0)-R27- wherein R4, R5, Rg, R7, R2g and R27 are as defined therein. 5. The compound according to Claim 1 wherein n is 0, Z is -CH2-, and R3 is R4-C(0)-Rs- wherein R4 is (R1 1 )(R12)N- as defined therein and R5 is alkylene. 6. The compound according to Claim 1 wherein n is 0, Z is -CH2-, R1 is Ioweralkyl, and R3 is R4-C(0)-Rs- wherein R4 is (R1 1 )(R12)N- as defined therein and R5 is alkylene. 7. The compound according to Claim 1 wherein n is 0, Z is -CH2-, R1 is alkenyl, and R3 is R4-C(0)-Rs- wherein R4 is (R1 1 )(R12)N- as defined therein and R5 is alkylene. 8. The compound according to Claim 1 wherein n is 0, Z is -CH2-, Ri is heterocyclic (alkyl), and R3 is R4-C(0)-Rs- wherein R4 is (R1 1 )(R12)N- as defined therein and R5 is alkylene. 9. The compound according to Claim 1 wherein n is 0, Z is -CH2-, Rl is aryloxyalkyl, and R3 is R4-C(0)-Rs- wherein R4 is (R-| 1 )(R12)N- as defined therein and R5 is alkylene. 10. The compound according to Claim 1 wherein n is 0, Z is -CH2-, Rl is arylalkyi, and R3 is R4-C(0)-Rs- wherein R4 is (R1 1 )(R12)N- as defined therein and R5 is alkylene. 1 1. The compound according to Claim 1 wherein n is 0, Z is -CH2-, R1 is aryl, and R3 is R4-C(0)-Rs- wherein R4 is (Rn )(Ri 2)N- as defined therein and R5 is alkylene. 12. The compound according to Claim 1 wherein n is 0, Z is -CH2-. R1 is (N-alkanoyl-N-alkyl)aminoalkyl, and R3 is R4-C(0)-R5- wherein R4 is (R1 1 )(R12)N- as defined therein and R5 is alkylene. 13. The compound according to Claim 1 wherein n is 0, Z is -CH2-, Rl is alkylsulfonylamidoalkyl, and R3 is R4-C(0)-Rs- wherein R4 is (R1 1 )(R12)N- as defined therein and R5 is alkylene. 14. The compound according to Claim 1 wherein n is 0, R is tetrazolyl or -C(0)2-G wherein G is hydrogen or a carboxy protecting group or R is tetrazolyl or R is -C(0)-NHS(0)2R-j g wherein R- j g is Ioweralkyl, haloalkyi or aryl, Z is -CH2-, Ri and R2 are independently selected from (i) Ioweralkyl, (ii) alkenyl, (iii) substituted aryl wherein aryl is phenyl substituted with one, two or three substituents independently selected from Ioweralkyl, alkoxy, halo, alkoxyalkoxy and carboxyalkoxy and (iv) heterocyclic (alkyl), (v) arylalkyi, (vi) aryloxyalkyl, (vii) (N-alkanoyl-N-alkyl)aminoalkyl, and (viii) alkylsulfonylamidoalkyl, and R3 is R4-C(0)-Rs- wherein R4 is (R1 1 )(R12)N- wherein R-j - j and R12 are independently selected from Ioweralkyl, haloalkyi, alkoxyalkyi, haloalkoxyalkyi, aryl, hydroxyalkyi, alkoxy, aminoaikyl, trialkylaminoalkyl, heterocyclic, and arylalkyi and R5 is alkylene; or R3 is R4-C(0)-N(R2θ)- R 8" or R6-S(0)2-N(R21 )-Rl θ* wherein R4 is Ioweralkyl, aryl, alkoxy, alkylamino, aryloxy or arylalkoxy and Rβ is Ioweralkyl, haloalkyi, alkoxyalkyi, haloalkoxyalkyi, aryl or arylalkyi, Re and R10 are alkylene and R20 and R21 are Ioweralkyl; or R3 is Rg-S(0)2-R7- or R26-S(0)-R27- wherein Rg is Ioweralkyl or haloalkyi, R7 is alkylene, R26 is Ioweralkyl and R27 is alkylene. 15. The compound according to Claim 1 wherein n is 0, R is -C(0)2-G wherein G is hydrogen or a carboxy protecting group, tetrazolyl or -C(0)-NHS(0)2R -| g wherein R-j is Ioweralkyl, haloalkyi or aryl, Z is -CH2-, Rl is (i) Ioweralkyl or (ii) alkenyl, R 2 is substituted or unsubstituted 1 ,3-benzodioxolyl, 7-methoxy-1 ,3-benzodioxolyl, 1 ,4- benzodioxanyl, 8-methoxy-1 ,4-benzodioxanyl, dihydrobenzofuranyl, benzofuranyl, 4-methoxyphenyl, dimethoxyphenyl, fluorophenyl or difluorophenyl wherein the substituent is selected from Ioweralkyl, alkoxy and halogen and R3 is R4-C(0)-R5- wherein R5 is alkylene and R4 is (R1 1 )(R12)N- wherein R-j -j and R12 are independently selected from Ioweralkyl, aryl, hydroxyalkyi, alkoxy, aminoaikyl, trialkylaminoalkyl, and heterocyclic. 16. The compound according to Claim 1 wherein n is 0, R is -C(0)2-G wherein G is hydrogen or a carboxy protecting group, tetrazolyl or -C(0)-NHS(0)2R -| g wherein R-j g is Ioweralkyl, haloalkyi or aryl, Z is -CH2-, Rl is (i) hetrerocyclic (alkyl), (ii) aryloxyalkyl, (iii) aryalkyi, or (iv) aryl, R is substituted or unsubstituted 1 ,3- benzodioxolyl, 7-methoxy-1 ,3-benzodioxolyl, 1 ,4-benzodioxanyl, 8- methoxy-1 ,4-benzodioxanyl, dihydrobenzofuranyl, benzofuranyl, 4- methoxyphenyl, dimethoxyphenyl, fluorophenyl or difluorophenyl wherein the substituent is selected from Ioweralkyl, alkoxy and halogen and R3 is R4-C(0)-Rs- wherein R5 is alkylene and R4 is (R1 1 )(R12)N- wherein R-J -J and R12 are independently selected from Ioweralkyl, aryl, hydroxyalkyi, alkoxy, aminoaikyl, trialkylaminoalkyl, and heterocyclic. 17. The compound according to Claim 1 wherein n is 0, R is -C(0)2-G wherein G is hydrogen or a carboxy protecting group, tetrazolyl or -C(0)-NHS(0)2R -| 6 wherein R^ is Ioweralkyl or haloalkyi, Z is -CH2-, Rl is (i) phenyl, or (ii) substituted or unsubstituted 4- methoxyphenyl, 4-fluorophenyl, 2-fluorophenyl, 4-methylphenyl, 4- trifluoromethylphenyl, 4-pentafluoroethylphenyl, 4- methoxymethoxyphenyl, 4-hydroxyphenyl, 4-ethylphenyl, 1 ,3- benzodioxolyl, 1 ,4-benzodioxanyl or dihydrobenzofuranyl wherein the substituent is selected from alkoxy, alkoxyalkoxy and carboxyalkoxy, R 2 is 1 ,3-benzodioxolyl, 1 ,4-benzodioxanyl, dihydrobenzofuranyl, benzofuranyl, 4-methoxyphenyl, dimethoxyphenyl, fluorophenyl or difluorophenyl and R3 is R4-C(0)-Rs- wherein R5 is alkylene and R4 is (R1 1 )(R12)N- wherein R1 1 and are independently selected from haloalkyi, haloalkoxyalkyi, hydroxyalkyi, alkoxy, aminoaikyl, trialkylaminoalkyl, aryl, and heterocyclic. 18. The compound according to Claim 1 wherein n is 0, R is -C(0)2-G wherein G is hydrogen or a carboxy protecting group, tetrazolyl or -C(0)-NHS(0)2R -j g wherein R 1 6 is Ioweralkyl or haloalkyi, Z is -CH2-, l is substituted or unsubstituted 4-methoxyphenyl, 4- fluorophenyl, 2-fluorophenyl, 4-methylphenyl, 4-trifluoromethylphenyl, 4-pentafluoroethylphenyl, 4-methoxymethoxyphenyl, 4-hydroxyphenyl, 4-ethylphenyl, 1 ,3-benzodioxolyl, 1 ,4-benzodioxanyl or dihydrobenzofuranyl wherein the substituent is selected from alkoxy, alkoxyalkoxy and carboxyalkoxy, R is 1 ,3-benzodioxolyl, 1 ,4- benzodioxanyl, dihydrobenzofuranyl, benzofuranyl, 4-methoxyphenyl, dimethoxyphenyl, fluorophenyl or difluorophenyl and R3 is R4-C(0)-Rs- wherein R5 is alkylene and R4 is (R1 1 )(R12)N- wherein R- j - j and R-J 2 are independently selected from haloalkyi, haloalkoxyalkyi, hydroxyalkyi, alkoxy, aminoaikyl, trialkylaminoalkyl, aryl, and heterocyclic. 19. The compound according to Claim 1 wherein n is 0, R is -C(0)2-G wherein G is hydrogen or a carboxy protecting group, tetrazolyl or -C(0)-NHS(0)2R - j wherein R- j g is Ioweralkyl or haloalkyi, Z is -CH2-, Ri is (i) phenyl, or (ii) substituted or unsubstituted 4- methoxyphenyl, 4-fluorophenyl, 2-fluorophenyl, 4-methylphenyl, 4- trifluoromethylphenyl, 4-pentafluoroethylphenyl, 4- methoxymethoxyphenyl, 4-hydroxyphenyl, 4-ethylphenyl, 1 ,3- benzodioxolyl, 1 ,4-benzodioxanyl or dihydrobenzofuranyl wherein the substituent is selected from alkoxy, alkoxyalkoxy and carboxyalkoxy, R 2 is 1 ,3-benzodioxolyl, 1 ,4-benzodioxanyl, dihydrobenzofuranyl, benzofuranyl, 4-methoxyphenyl, dimethoxyphenyl, fluorophenyl or difluorophenyl and R3 is R4-C(0)-Rs- wherein R5 is alkylene and R4 is (R1 1 )(R12)N- wherein R-j -j and R-J2 are independently selected from aminoaikyl, trialkylaminoalkyl, aryl, and heterocyclic. 20. The compound according to Claim 1 wherein n is 0, R is -C(0)2-G wherein G is hydrogen or a carboxy protecting group, tetrazolyl or -C(0)-NHS(0)2R-| g wherein R-| g is Ioweralkyl or haloalkyi, Z is -CH2-, R1 is substituted or unsubstituted 4-methoxyphenyl, 4- fluorophenyl, 2 -fluorophenyl, 4-methylphenyl, 4-trifluoromethylphenyl, 4-pentafluoroethylphenyl, 4-methoxymethoxyphenyl, 4-hydroxyphenyl, 4-ethylphenyl, 1 ,3-benzodioxolyl, 1 ,4-benzodioxanyl or dihydrobenzofuranyl wherein the substituent is selected from alkoxy, alkoxyalkoxy and carboxyalkoxy, R2 is 1 ,3-benzodioxolyl, 1 ,4- benzodioxanyl, dihydrobenzofuranyl, benzofuranyl, 4-methoxyphenyl, dimethoxyphenyl, fluorophenyl or difluorophenyl and R3 is R4-C(0)-Rs- wherein R5 is alkylene and R4 is (Rn)(Ri2)N- wherein R-J -J and R- j 2 are independently selected from aminoaikyl, trialkylaminoalkyl, aryl, and heterocyclic. 21. The compound according to Claim 1 of the formula: wherein Z is -C(R18)(R19)- or -C(O)- wherein R18 and R19 are independently selected from hydrogen and Ioweralkyl; n is 0 or 1 ; R is -(CH2)m-W wherein m is an integer from 0 to 6 and W is (a) -C(0)2-G wherein G is hydrogen or a carboxy protecting group, (b) -PO3H2, (c) -P(0)(OH)E wherein E is hydrogen, Ioweralkyl or arylalkyi, (d) -CN, (e) -C(0)NHR17 wherein R17 is Ioweralkyl, (f) alkylaminocarbonyl, (g) dialkylaminocarbonyl, (h) tetrazolyl, (i) hydroxy, (j) alkoxy, (k) sulfonamido, (I) -C(0)NHS(0)2 16 wherein R-| 6 is Ioweralkyl, haloalkyi, aryl or dialkylamino, (m) -S(0)2NHC(0)R16 wherein R-jg is defined as above, R l is selected from Ioweralkyl, alkenyl, haloalkyi, haloalkoxyalkyi, cycloalkylalkyl, arylalkyi, aryloxyalkyl, arylalkoxyalkyi, (N-alkanoyl-N- aikyl)aminoalkyl, alkylsulfonylamidoalkyl, and (heterocyclic)alkyl; R2 is selected from the group consisting of hydrogen, Ioweralkyl, alkenyl, alkynyl, alkoxyalkyi, alkoxycarbonylalkyl, hydroxyalkyi, haloalkyi, haloalkoxyalkyi, alkoxyalkoxyalkyl, thioalkoxyalkoxyalkyi, (N- alkanoyl-N-alkyl)aminoalkyl, alkylsulfonylamidoalkyl, cycloalkyi, cycloalkylalkyl, aminocarbonylalkyl, alkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, aminocarbonylalkenyl, alkylaminocarbonylalkenyl, dialkylaminocarbonylalkenyl, hydroxyalkenyl, aryl, arylalkyi, aryloxyalkyl, arylalkoxyalkyi, heterocyclic, (heterocyclic)alkyl and (R a aM R bb) N " R cc" wherein R aa is aryl or arylalkyi, Rbb is hydrogen or alkanoyl and R cc is alkylene, with the proviso that one or both of R- | and R2 is other than hydrogen; R3 is (a) R4-C(0)-R5-, R4-R5a-. R6-S(0)2-R7- or R26-S(0)-R27- wherein R5 is (i) a covalent bond, (ii) alkylene, (iii) alkenylene, (iv) -N(R20)-R8- or -R 8a - N ( R 2θ)- R 8- wherein Re and Rg a are independently selected from the group consisting of alkylene and alkenylene and R20 is hydrogen, Ioweralkyl, alkenyl, haloalkyi, alkoxyalkyi, haloalkoxyalkyi, cylcoalkyl or cycloalkylalkyl or (v) -O-R9- or -Rga'O-Rg- wherein R9 and Rg a are independently selected from alkylene; R5a is (i) alkylene or (ii) alkenylene; R7 is (i) a covalent bond, (ii) alkylene, (iii) alkenylene or (iv) -N(R21 )-R10- or -R-| 0a" N ( R 2l )-Rl 0- wherein R-J O and R-j rja are independently selected from the group consisting of alkylene and alkenylene and R21 is hydrogen, Ioweralkyl, alkenyl, haloalkyi, alkoxyalkyi, haloalkoxyalkyi, aryl or arylalkyi; R4 and R6 are independently selected from the group consisting of (i) (Rn )(Ri 2)N- wherein R1 1 and R12 are independently selected from 1 ) hydrogen, 2) Ioweralkyl, 3) haloalkyi, 4) alkoxyalkyi, 5) haloalkoxyalkyi, 6) alkenyl, 7) alkynyl, 8) cycloalkyi, 9) cycloalkylalkyl, 10) aryl, (11) heterocyclic, ; 12) arylalkyi, and ;13) (heterocyclic)alkyl, 14) hydroxyalkyi, 15) alkoxy, ;16) aminoaikyl, and [ 17) trialkylaminoalkyl , (ϋ) Ioweralkyl, (iii) alkenyl, (iv) alkynyl, (v) cycloalkyi , (vi) cycloalkylalkyl, (vii) aryl, (viii) arylalkyi, (ix) heterocyclic, (x) (heterocyclic)alkyl, (xi) alkoxyalkyi, (xii) hydroxyalkyi, (xiii) haloalkyi, (xiv) haloalkenyl, (xv) haloalkoxyalkyi, 100 (xvi) haloalkoxy, (xvii) alkoxyhaloalkyl, (xviii) alkylaminoalkyl, (xix) diaikylaminoalkyl, (xx) alkoxy, and 105 (xxi) wherein z is 0-5 and R a is alkylene; 110 R26 is (i) Ioweralkyl, (ii) haloalkyi, (iii) alkenyl, (iv) alkynyl, (v) cycloalkyi, (vi) cycloalkylalkyl, (vii) aryl, (viii) arylalkyi, (ix) heterocyclic, (x) (heterocyclic)alkyl, (xi) alkoxyalkyi or (xii) alkoxy- substituted haloalkyi; and 115 R27 is alkylene or alkenylene; (b) R22-0-C(0)-R23- wherein R22 is a carboxy protecting group or heterocyclic and R23 is (i) a covalent bond, (ii) alkylene, (iii) alkenylene or (iv) 120 -N(R24)-R25-wherein R25 is alkylene and R24 is hydrogen or Ioweralkyl, (c) Ioweralkyl, (d) alkenyl, (e) alkynyl, 125 (f ) cycloalkyi, (g) cycloalkylalkyl, (h) aryl , ( i) arylalkyi, (j ) aryloxyalkyl, 130 (k) heterocyclic, (I ) (heterocyclic)alkyl, (m) alkoxyalkyi, (n) alkoxyalkoxyalkyl, o r (o) R13-C(0)-CH(R14)- 135 wherein R13 is amino, alkylamino or dialkylamino and R14 is aryl or R 15-C(0)- wherein R15 is amino, alkylamino or dialkylamino; or a pharmaceutically acceptable salt thereof. 22. The compound according to Claim 21 wherein n is 0 and Z is -CH2-. 23. The compound according to Claim 21 wherein n is 1 and Z is -CH2-. 24. The compound according to Claim 1 wherein n is 0, Z is -CH2-, and R3 is R4-C(0)-Rs- , R6-SO2-R7- or R26-S(0)-R27- wherein R4, R5, Rg, R7, R26 ancl R 27 are as defined therein. 25. The compound according to Claim 1 wherein n is 0, Z is -CH2-, and R3 is R4-C(0)-Rs- wherein R4 is (R11 )(R12)N- as defined therein and R5 is alkylene. 26. The compound according to Claim 21 wherein n is 0, Z is -CH2-, Rl is Ioweralkyl, and R3 is R4-C(0)-Rs- wherein R4 is (R1 1 )(R12)N- as defined therein and R5 is alkylene. 27. The compound according to Claim 21 wherein n is 0, Z is -CH2-, Rl is alkenyl, and R3 is R4-C(0)-Rs- wherein R4 is (Rn )(Ri 2)N- as defined therein and R5 is alkylene. 28. The compound according to Claim 21 wherein n is 0, Z is -CH2-, Rl is heterocyclic (alkyl), and R3 is R4-C(0)-Rs- wherein R4 is (R1 1 )(R12)N- as defined therein and R5 is alkylene. 29. The compound according to Claim 21 wherein n is 0, Z is -CH2-, Rl is aryloxyalkyl, and R3 is R4-C(0)-Rs- wherein R4 is (R1 1 )(R12)N- as defined therein and R5 is alkylene. 30. The compound according to Claim 21 wherein n is 0, Z is -CH2-, Rl is arylalkyi, and R3 is R4-C(0)-Rs- wherein R4 is (R1 1)(R12)N- as defined therein and R5 is alkylene. 31. The compound according to Claim 21 wherein n is 0, Z is -CH2-. l is aryl, and R3 is R4-C(0)-Rs- wherein R4 is (Rn )(Ri2)N- as defined therein and R5 is alkylene. 32. The compound according to Claim 21 wherein n is 0, Z is -CH2-, Rl is (N-alkanoyl-N-alkyl)aminoalkyl, and R3 is R4-C(0)-Rs- wherein R4 is (R1 1 )(R12)N- as defined therein and R5 is alkylene. 33. The compound according to Claim 21 wherein n is 0, Z is -CH2-, R1 is alkylsulfonylamidoalkyl, and R3 is R4-C(0)-Rs- wherein R4 is (R1 1 )(R12)N- as defined therein and R5 is alkylene. 34. The compound according to Claim 21 wherein n is 0, R is tetrazolyl or -C(0)2-G wherein G is hydrogen or a carboxy protecting group or R is tetrazolyl or R is -C(0)-NHS(0)2R ι g wherein R-j g is Ioweralkyl, haloalkyi or aryl, Z is -CH2-, Rl and R2 are independently selected from (i) Ioweralkyl, (ii) alkenyl, (iii) substituted aryl wherein aryl is phenyl substituted with one, two or three substituents independently selected from Ioweralkyl, alkoxy, halo, alkoxyalkoxy and carboxyalkoxy and (iv) heterocyclic (alkyl), (v) arylalkyi, (vi) aryloxyalkyl, (vii) (N-alkanoyl-N-alkyl)aminoalkyl, and (viii) alkylsulfonylamidoalkyl, and R3 is R4-C(0)-Rs- wherein R4 is (R1 1 )( R 12)N- wherein R- j - j and R12 are independently selected from Ioweralkyl, haloalkyi, alkoxyalkyi, haloalkoxyalkyi, aryl, hydroxyalkyi, alkoxy, aminoaikyl, trialkylaminoalkyl, heterocyclic, and arylalkyi and R5 is alkylene; or R3 is R4-C(0)-N(R2θ)-R8 * or R6-S(0)2-N(R21 )-R10- wherein R4 is Ioweralkyl, aryl, alkoxy, alkylamino, aryloxy or arylalkoxy and Rβ is Ioweralkyl, haloalkyi, alkoxyalkyi, haloalkoxyalkyi, aryl or arylalkyi, Re and R10 are alkylene and R20 and R21 are Ioweralkyl; or R3 is Rβ-S(0)2-R7- or R26-S(0)-R27- wherein Rg is loweralkyl or haloalkyi, R7 is alkylene, R26 is Ioweralkyl and R27 is alkylene. 35. The compound according to Claim 21 wherein n is 0, R is -C(0)2-G wherein G is hydrogen or a carboxy protecting group, tetrazolyl or -C(0)-NHS(0)2R -| g wherein R-j g is Ioweralkyl, haloalkyi or aryl, Z is -CH2-, Rl is (i) Ioweralkyl or (ii) alkenyl, R2 is substituted or unsubstituted 1 ,3-benzodioxolyl, 7-methoxy-1 ,3-benzodioxolyl, 1 ,4- benzodioxanyl, 8-methoxy-1 ,4-benzodioxanyl, dihydrobenzofuranyl, benzofuranyl, 4-methoxyphenyl, dimethoxyphenyl, fluorophenyl or difluorophenyl wherein the substituent is selected from Ioweralkyl, alkoxy and halogen and R3 is R4-C(0)-Rs- wherein R5 is alkylene and R4 is (R11 )(R12)N- wherein R-j -| and R12 are independently selected from Ioweralkyl, aryl, hydroxyalkyi, alkoxy, aminoaikyl, trialkylaminoalkyl, and heterocyclic. 36. The compound according to Claim 21 wherein n is 0, R is -C(0)2-G wherein G is hydrogen or a carboxy protecting group, tetrazolyl or -C(0)-NHS(0)2R -| g wherein R-j g is Ioweralkyl, haloalkyi or aryl, Z is -CH2-, Rl is (i) hetrerocyclic (alkyl), (ii) aryloxyalkyl, (iii) aryalkyi, or (iv) aryl, R2 is substituted or unsubstituted 1 ,3- benzodioxolyl, 7-methoxy-1 ,3-benzodioxolyl, 1 ,4-benzodioxanyI, 8- methoxy-1 ,4-benzodioxanyl, dihydrobenzofuranyl, benzofuranyl, 4- methoxy phenyl, dimethoxyphenyl, fluorophenyl or difluorophenyl wherein the substituent is selected from Ioweralkyl, alkoxy and halogen and R3 is R4-C(0)-R5- wherein R5 is alkylene and R4 is (R1 1 )(R12)N- wherein R- j - j and R12 are independently selected from Ioweralkyl, aryl, hydroxyalkyi, alkoxy, aminoaikyl, trialkylaminoalkyl, and heterocyclic. 37. The compound according to Claim 21 wherein n is 0, R is -C(0)2-G wherein G is hydrogen or a carboxy protecting group, tetrazolyl or -C(0)-NHS(0) 2 R - | g wherein R- j g is Ioweralkyl or haloalkyi, Z is -CH2-, R l is (i) phenyl, or (ii) substituted or unsubstituted 4-methoxyphenyl, 4-fluorophenyl, 2-fluorophenyl, 4-methylphenyl, 4- trifluoromethylphenyl, 4-pentafluoroethylphenyl, 4- methoxymethoxyphenyl, 4-hydroxyphenyl, 4-ethylphenyl, 1 ,3- benzodioxolyl, 1 ,4-benzodioxanyl or dihydrobenzofuranyl wherein the substituent is selected from alkoxy, alkoxyalkoxy and carboxyalkoxy, R 2 is 1 ,3-benzodioxolyl, 1 ,4-benzodioxanyl, dihydrobenzofuranyl, benzofuranyl, 4-methoxyphenyl, dimethoxyphenyl, fluorophenyl or difluorophenyl and R3 is R4-C(0)-R5- wherein R5 is alkylene and R4 is (R11 )(R12)N- wherein R-| i and R^ 2 are independently selected from haloalkyi, haloalkoxyalkyi, hydroxyalkyi, alkoxy, aminoaikyl, trialkylaminoalkyl, aryl, and heterocyclic. 38. The compound according to Claim 21 wherein n is 0, R is -C(0)2-G wherein G is hydrogen or a carboxy protecting group, tetrazolyl or -C(0)-NHS(0)2R -| g wherein R-| g is Ioweralkyl or haloalkyi, Z is -CH2-, Ri is substituted or unsubstituted 4-methoxyphenyl, 4- fluorophenyl, 2-fluorophenyl, 4-methylphenyl, 4-trifluoromethylphenyl, 4-pentafluoroethylphenyl, 4-methoxymethoxyphenyl, 4-hydroxyphenyl, 4-ethylphenyl, 1 ,3-benzodioxolyl, 1 ,4-benzodioxanyl or dihydrobenzofuranyl wherein the substituent is selected from alkoxy, alkoxyalkoxy and carboxyalkoxy, R2 is 1 ,3-benzodioxolyl, 1 ,4- benzodioxanyl, dihydrobenzofuranyl, benzofuranyl, 4-methoxyphenyl, dimethoxyphenyl, fluorophenyl or difluorophenyl and R3 is R4-C(0)-Rs- wherein R5 is alkylene and R4 is (R1 1 )(R12)N- wherein R- j - ) and R12 are independently selected from haloalkyi, haloalkoxyalkyi, hydroxyalkyi, alkoxy, aminoaikyl, trialkylaminoalkyl, aryl, and heterocyclic. 39. A compound selected from the group consisting of fraπs-frans-2-(4-Methoxphenyl)-4-(1 ,3-benzodioxol-5-yl)-1 -[3-(N- propyl-N-π-pentanesulfonylamino)propyl]-pyrrolidine-3- carboxylic acid; trans, frans-2-(4-Methoxymethoxyphenyl)-4-( 1 ,3-benzodioxol-5-yl)-1 - (2-(N-propyl-N-n-pentanesulfonylamino)ethyl]pyrrolidine-3- carboxylic acid; frans, frans-2-(3,4-Dimethoxyphenyl)-4-(1 ,3-benzodioxol -5-yl)-1 -[2- (N-propyl-N-n-pentanesulfonylamino)ethyl]pyrrolidine-3- carboxylic acid; trans, fraπs-2-(3,4-Dimethoxyphenyl)-4-(1 ,3-benzodioxol-5-y I)- 1 -[2- (N-propyl-N-n-hexanesulfonylamino)ethyl]pyrrolidine-3- carboxylic acid; trans, trans-2-( 4-Propoxyphenyl)-4-(1 ,3-benzodioxol-5-yl)-1 -[2-(N- propyl-N-π-pentanesulfonylamino)ethyl]pyrrolidine-3-carboxylic acid; frans, frans-2-(3,4-Dif luorophenyl)-4-(1 ,3-benzodioxol-5-yl)-1 -(((N,N- dibutylamino)carbonyl)methyl)-pyrrolidine-3-carboxylic acid; trans, frans-2-(3,4-Difluorophenyl)-4-(1 ,3-benzodioxol-5-yl)-1 -[2-(N- propyl-N-n-pentanesulfonylamino)ethyl]pyrrolidine-3-carboxylic acid; trans, frans-2-(3-Fluoro-4-methoxyphenyl)-4-(1 ,3-benzodioxol-5-yl)- 1 -[2-(N-propyl-N-n-hexanesulfonylamino)ethyl]pyrrolidine-3- carboxylic acid; trans, frans-2-(3-Fluoro-4-methoxyphenyl)-4-(1 ,3-benzodioxol-5-yl)- 1 -(2-(N-propyl-N-(3-chloropropanesulfonyl)amino)ethyl)- pyrrolidine-3-carboxylic acid; trans, fraπs-2-(3-Fluoro-4-methoxyphenyl)-4-(1 ,3-benzodioxol-5-yl)- 1 -(2-(N-isobutyl-N-(3- chloropropanesulfonyl)amino)ethyl)pyrrolidine-3-carboxylic acid; frans, frans-2-(3-Fluoro-4-methoxyphenyl)-4-(1 ,3-benzodioxol-5-yl)- 1 -[2-(N-propyl-N-(4- methylbutanesulfonyl)amino)ethyl]pyrrolidine-3-carboxylic acid; trans, frans-2-(4-Methoxy-3-fluorophenyl)-4-(7-methoxy- 1 ,3- benzodioxol-5-yl)-1 -[2-(N-propyl-N-(n- pentanesulfonyl)amino)ethyl]pyrrolidine-3-carboxylic acid; trans, frans-2-(3-Fluoro-4-methoxy phenyl)-4-(1 , 3-benzodioxol-5-yl)- 1 -[2-(N-propyl-N-(2,2,3,3,3-ρentafluoropropoxyethanesulfonyl)- amino)ethyl]pyrrolidine-3-carboxylic acid; trans, frans-2-(1 ,4-Benzodioxan-6-yl)-4-(7-methoxy-1 ,3-benzodioxol- 5-yl)- 1 -[2-(N-propyl-N-(n- pentanesulfonyl)amino)ethyl]pyrrolidine-3-carboxylic acid; frans,frans-2-(3-Fluoro-4-methoxyphenyl)-4-(1 ,3-benzodioxol-5-yl)- 1 -(2-(N-isobutyl-N-(pentanesulfonylamino)ethyl)pyrrolidine-3- carboxylic acid; trans, frans-2-(3-Fluoro-4-methoxypheny l)-4-(1 , 3-benzodioxol-5-y I)- 1 -(2-(N-(2-methoxyethyl)-N-(3-chloropropanesulfonyl)amino)- ethyl)pyrrolidine-3-carboxylic acid; trans, frans-2-(3-Fluoro-4-methoxyphenyl)-4-(1 ,3-benzodioxol-5-yl)- 1 -(2-(N-(2-methoxyethyl)-N- (pentanesulfonyl)amino)ethyl)pyrrolidine-3-carboxylic acid; trans, frans-2-(3-Fluoro-4-methoxypheny l)-4-(1 , 3-benzodioxol-5-yl)- 1 -[2-(N-propyl-N-((2,2,2-trifluoroethoxyethane)sulfonyl)amino)- ethyl]pyrrolidine-3-carboxylic acid; trans, frans-2-(3-Fluoro-4-methoxy phenyl)-4-(1 , 3-benzodioxol-5-yl)- 1 -(2-(N-(2-methoxyethyl)-N-(butanesulfonylamino)ethyl)- pyrrolidine-3-carboxylic acid; trans, frans-2-(3-Fluoro-4-methoxyphenyl)-4-( 1 ,3-benzodioxol-5-yl)- 1 -[2-(N-propyl-N-(2- methylpropanesulfonyl)amino)ethyl]pyrrolidine-3-carboxylic acid; and trans, frans-2-(3-Fluoro-4-methoxypheny l)-4-(1 , 3-benzodioxol-5-yl)- 1 -(2-(N-isobutyl-N-(butanesulfonylamino))ethyl)pyrrolidine-3- carboxylic acid; trans, frans-2-(2-Methylpentyl)-4-(1 ,3-benzodioxol-5-yl)-1 -(N,N- dibutylaminocarbonylmethyl)-pyrrolidine-3-carboxylic acid; trans, frans-2-(2,2-Dimethylpentyl)-4-(1 ,3-benzodioxol-5-yl)- 1 -(N,N- dibutylaminocarbonylmethyl)-pyrrolidine-3-carboxylic acid; trans ,frans-2-(2-(1 ,3-Dioxo-2-yl)ethyl)-4-( 1 ,3-benzodioxol-5-yl)- 1 - [(dibutyl amino)carbonylmethyl]-pyrrolidine-3-carboxylic acid; trans, frans-2-(2-(2-Tetrahydro-2 H-pyran)ethy l)-4-(1 , 3-benzodioxol- 5-yl)-1 -[(dibutyl amino)carbonylmethyl]-pyrrolidine-3-carboxylic acid; trans, frans-2-(2,2,4-Trimethyl-3-pentenyl)-4-(1 ,3-benzodioxol-5- yl)- 1 -(N,N-dibutylaminocarbonylmethyl)-pyrrolidine-3-carboxylic acid; trans, frans-2-(2,2,-Dimethyl-2-(1 ,3-dioxolan-2-yl)ethyl)-4-(1 ,3- benzodioxol-5-yl)-1 -(N,N-dibutylaminocarbonylmethyl)- pyrrolidine-3-carboxylic acid; 80 trans, frans-2-(2-(1 ,3-D ' ιoxo-2-yl)ethyl)-4-(1 ,3-benzodioxol-5-yl)-1 - [[Λ/-4-heptyl-Λ/-(2-methyl-3-fluorophenyl)] amino carbonylmethyl]-pyrrolidine-3-carboxylic acid; trans, frans-2-(2-(1 ,3-Dioxol-2-yl)ethyl)-4-(7-methoxy-1 ,3- benzodioxol-5-yl)-1 -[(dibutyl amino)carbonylmethyl]-pyrrolidine- 85 3-carboxylic acid trans, frans-2-((2-Methoxyphenoxy)-methyl)-4-(7-methoxy-1 ,3- benzodioxol-5-yl)-1 -[(dibutyl amino)carbonylmethyl]-pyrrolidine- 3-carboxylic acid; t;2S, 3fl,4S -2-(2,2-Dimethylpentyl)-4-(1 ,3-benzodioxol-5-yl)-1 -(N-4- 90 heptyl-N-(4-fluoro-3-methylphenyl))aminocarbonylmethyl)- pyrrolidine-3-carboxylic acid; trans, frans-2-(2-(2-Oxopyrrolidin-1 -yl)ethyl)-4-(1 ,3-benzodioxol-5- yl)-1 -[(dibutyl amino)carbonylmethyl]-pyrrolidine-3-carboxylic acid; 95 trans, frans-2-(2-( 1 ,3-Dioxol-2-yl)ethyl)-4-(7-methoxy-1 ,3- benzodioxol-5-yl)-1 -(N-4-heptyl-N-(4-fluoro-3- methylphenyl))aminocarbonylmethyl)-pyrrolidine-3-carboxylic acid; trans, frans-2-(2,2-Dimethylpentyl)-4-(7-methoxy-1 ,3-benzodioxol-5- 100 yl)-1 -[(dibutyl amino)carbonylmethyl]-pyrrolidine-3-carboxylic acid; frans,frans-2-(2,2-dimethylpentyl)-4-(2,3-dihydro-benzofuran-5-yl)- 1 -[(dibutyl amino)carbonylmethyl]-pyrrolidine-3-carboxylic acid; trans, trans-2-(2, 2, -Dimethy l-2-(1 , 3-dioxolan-2-yl)ethyl)-4-(7- 105 methoxy-1 ,3-benzodioxol-5-yl)-1 -(N,N- dibutylaminocarbonylmethyl)-pyrrolidine-3-carboxylic acid; trans, frans-2-(2-(2-Methoxyphenyl)-ethyl)-4-(7- methoxy- 1 , 3- benzodioxol-5-yl)-1 -[(dibutyl amino)carbonylmethyl]-pyrrolidine- 3-carboxylic acid; 110 trans, frans-2-(2,2-Dimethyl-3-(E>-pentenyl)-4-(7-methoxy-1 ,3- benzodioxol-5-yl)-1 -(N,N-dibutylaminocarbonylmethyl)- pyrrolidine-3-carboxylic acid; trans, frans-2-(2-(2-pyridyl)ethyl)-4-(1 ,3-benzodioxol-5-yl)-1 -(N ,N- dibutylaminocarbonylmethyl)-pyrrolidine-3-carboxylic acid; 115 (2S, 3R, 4S -2-(2-(2-oxopyrrolidin-1 -yl)ethyl)-4-(1 ,3-benzodioxol-5- yl)- 1 -(N,N-dibutylaminocarbonylmethyl)-pyrrolidine-3-carboxylic acid; {2S, 3R, 4S)-2-(2-(2-oxopyrrolidin-1 -yl)ethyl)-4-(1 ,3-benzodioxol-5- yl)-1 -(N-4-heptyl-N-(4-fluoro-3- 120 methylphenyl))aminocarbonylmethyl)-pyrrolidine-3-carboxylic acid; trans, frans-2-(2-(1 -pyrazoly l)ethyl)-4-( 1 ,3-benzodioxol-5-y I)- 1 - (N,N-dibutylaminocarbonylmethyl)-pyrrolidine-3-carboxylic acid; trans, frans-2-(4-Methoxyphenyl)-4-(1 ,3-benzodioxol-5-yl)-1 -[(N- 125 butyl-N-(4-dimethylaminobutyl)amino)carbonylmethyl]- pyrrolidine-3-carboxylic acid; f2fl,3r?,4S -2-(3-Fluoro-4-methoxyphenyl)-4-(1 ,3-benzodioxol-5-yl) 1 - (2-(N-propyl-N-pentanesulfonylamino)ethyl)-pyrrolidine-3- carboxylic acid; 130 or a pharmaceutically acceptable salt thereof. 40. A compound of the formula: 5 wherein n is 0 or 1 ; m is 0 to 6; W is (a) -C(0)2-G where G is hydrogen or a carboxy protecting group, (b) -PO3H2, (c) -P(0)(OH)E where E is hydrogen, Ioweralkyl or arylalkyi, (d) -CN, (e) -C(0)NHR-| 7 where R17 is Ioweralkyl, (f) alkylaminocarbonyl, (g) dialkylaminocarbonyl, (h) tetrazolyl, (i) hydroxy, (j) alkoxy, (k) sulfonamido, (I) -C(0)NHS(0)2R16 where R-|6 is Ioweralkyl, haloalkyi, phenyl or dialkylamino, (m) -S(0)2NHC(0)R16, -654- R -| is selected from Ioweralkyl, alkenyl, haloalkyi, haloalkoxyalkyi, alkoxyalkoxyalkyl, cycloalkylalkyl, aryl, arylalkyi, aryloxyalkyl, (heterocyclic)alkyl, (N-alkanoyl-N-alkyl)aminoalkyl, and alkylsulfonylamidoalkyl, and R2 is selected from the group consisting of hydrogen, Ioweralkyl, alkenyl, alkynyl, alkoxyalkyi, alkoxycarbonylalkyl, hydroxyalkyi, haloalkyi, haloalkoxyalkyi, alkoxyalkoxyalkyl, thioalkoxyalkoxyalkyi, (N-alkanoyl-N- alkyl)aminoalkyl, alkylsulfonylamidoalkyl, cycloalkyi, cycloalkylalkyl, aminocarbonylalkyl, alkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, aminocarbonylalkenyl, alkylaminocarbonylalkenyl, dialkylaminocarbonylalkenyl, hydroxy alkenyl, aryl, arylalkyi, aryloxyalkyl, arylalkoxyalkyi, heterocyclic, (heterocyclic)alkyl and (R aa )(Rbb)N-R cc - wherein R aa is aryl or arylalkyi, R is hydrogen or alkanoyl and R cc is alkylene, or a salt thereof. 41. The compound of Claim 40 wherein m is zero or 1; W is -CO2-G wherein G is hydrogen or a carboxy protecting group; or the substantially pure (+)- or (-)-isomer thereof. 42. The compound of Claim 40 wherein n and m are both 0; W is -CO2-G wherein G is hydrogen or a carboxy protecting group; and Ri is (i) Ioweralkyl, (ii) alkenyl, (iii) heterocyclic (alkyl), (iv) aryloxyalkyl, (v) arylalkyi, (vi) (N-alkanoyl-N-alkyl)aminoalkyl, (vii) alkylsulfonylamidoalkyl or (viii) substituted or unsubstituted 4- methoxy phenyl, 4-fluorophenyl, 3-fluorophenyl, 4-ethoxyphenyl, 4- ethylphenyl, 4-methylphenyl, 4-trifluoromethylphenyl, 4- pentafluoroethylphenyl, 3-fluoro-4-methoxyphenyl, 3-fluoro-4- ethoxyphenyl, 2-fluorophenyl, 4-methoxymethoxyphenyl, 4- hydroxyphenyl, 4-t-butylphenyl, 1 ,3-benzodioxolyl, 1 ,4-benzodioxanyl or dihydrobenzofuranyl wherein the substituent is selected from Ioweralkyl, haloalkyi, alkoxy, alkoxyalkoxy and carboxyalkoxy, and R2 is substituted or unsubstituted 1 ,3-benzodioxolyl, 7-methoxy-1 ,3- benzodioxolyl, 1 ,4-benzodioxanyl, 8-methoxy-1 ,4-benzodioxanyl, dihydrobenzofuranyl, benzofuranyl, 4-methoxyphenyl, dimethoxyphenyl, fluorophenyl or difluorophenyl wherein the substituent is selected from Ioweralkyl, alkoxy and halogen; or the substantially pure (+)- or (-)-isomer thereof. 43. The compound according to Claim 40 of the formula: wherein n is 0 or 1 ; m is 0 to 6; W is (a) -C(0)2-G where G is hydrogen or a carboxy protecting group, (b) -PO3H2, (c) -P(0)(OH)E where E is hydrogen, Ioweralkyl or arylalkyi, (d) -CN, (e) -C(0)NHR17 where R17 is Ioweralkyl, (f) alkylaminocarbonyl, (g) dialkylaminocarbonyl, (h) tetrazolyl, (i) hydroxy, (j) alkoxy, (k) sulfonamido, (I) -C(0)NHS(0)2 R 16 where R16 is Ioweralkyl, haloalkyi, phenyl or dialkylamino, -656- (m) -S(0)2NHC(0)R16, R l is selected from Ioweralkyl, alkenyl, haloalkyi, haloalkoxyalkyi, alkoxyalkoxyalkyl, cycloalkylalkyl, aryl, arylalkyi, aryloxyalkyl, (heterocyclic)alkyl, (N-alkanoyl-N-alkyl)aminoalkyl, and alkylsulfonylamidoalkyl, and R2 is selected from the group consisting of hydrogen, Ioweralkyl, alkenyl, alkynyl, alkoxyalkyi, alkoxycarbonylalkyl, hydroxyalkyi, haloalkyi, haloalkoxyalkyi, alkoxyalkoxyalkyl, thioalkoxyalkoxyalkyi, (N-alkanoyl-N- alkyl)aminoalkyl, alkylsulfonylamidoalkyl, cycloalkyi, cycloalkylalkyl, aminocarbonylalkyl, alkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, aminocarbonylalkenyl, alkylaminocarbonylalkenyl, dialkylaminocarbonylalkenyl, hydroxy alkenyl, aryl, arylalkyi, aryloxyalkyl, arylalkoxyalkyi, heterocyclic, (heterocyclic)alkyl and ( R aa)( R bb) N " R cc" wherein R aa is aryl or arylalkyi, Rb i hydrogen or alkanoyl and R cc is alkylene, or a salt thereof. 44. The compound according to Claim 43 wherein m is zero or 1; W is -CO2-G wherein G is hydrogen or a carboxy protecting group; or the substantially pure (+)- or (-)-isomer thereof. 45. The compound of Claim 43 wherein n and m are both 0; W is -CO2-G wherein G is hydrogen or a carboxy protecting group; and R-| is (i) Ioweralkyl, (ii) alkenyl, (iii) heterocyclic (alkyl), (iv) aryloxyalkyl, (v) arylalkyi, (vi) (N-alkanoyl-N-alkyl)aminoalkyl, (vii) alkylsulfonylamidoalkyl or (viii) substituted or unsubstituted 4- methoxyphenyl, 4-fluorophenyl, 3-fluorophenyl, 4-ethoxyphenyl, 4- ethylphenyl, 4-methylphenyl, 4-trifluoromethylphenyl, 4- pentafluoroethylphenyl, 3-fluoro-4-methoxyphenyl, 3-fluoro-4- ethoxyphenyl, 2-fluorophenyl, 4-methoxymethoxyphenyl, 4- hydroxyphenyl, 4-t-butylphenyl, 1 ,3-benzodioxolyl, 1 ,4-benzodioxanyl or dihydrobenzofuranyl wherein the substituent is selected from Ioweralkyl, haloalkyi, alkoxy, alkoxyalkoxy and carboxyalkoxy, and R 2 is substituted or unsubstituted 1 ,3-benzodioxolyl, 7-methoxy-1 ,3- benzodioxolyl, 1 ,4-benzodioxanyl, 8-methoxy-1 ,4-benzodioxanyl, dihydrobenzofuranyl, benzofuranyl, 4-methoxyphenyl, dimethoxyphenyl, fluorophenyl or difluorophenyl wherein the substituent is selected from loweralkyl, alkoxy and halogen; or the substantially pure (+)- or (-)-isomer thereof. 46. The substantially pure compound (+)-trans,trans-2-(4- Methoxyphenyl)-4-(1 ,3-benzodioxo-5-lyl)pyrrolidine-3-carboxylic acid; or a salt or ester thereof. 47. A compound of the formula wherein n is 0 or 1 ; m is 0 to 6; R5b is alkylene; Q is a leaving group; W is (a) -C(0)2-G where G is hydrogen or a carboxy protecting group, (b) -PO3H2, (c) -P(0)(OH)E where E is hydrogen, Ioweralkyl or arylalkyi, (d) -CN, (e) -C(0)NHR17 where R17 is Ioweralkyl, (f) alkylaminocarbonyl, (g) dialkylaminocarbonyl, (h) tetrazolyl, (i) hydroxy, (j) alkoxy, (k) sulfonamido, (I) -C(0)NHS(0)2R16 where R16 is Ioweralkyl, haloalkyi, phenyl or dialkylamino, (m) -S(0)2NHC(0)R16, R 1 is selected from Ioweralkyl, alkenyl, haloalkyi, haloalkoxyalkyi, alkoxyalkoxyalkyl, cycloalkylalkyl, aryl, arylalkyi, aryloxyalkyl, (heterocyclic)alkyl, (N-alkanoyl-N-alkyl)aminoalkyl, and alkylsulfonylamidoalkyl, and R2 is selected from the group consisting of hydrogen, Ioweralkyl, alkenyl, alkynyl, alkoxyalkyi, alkoxycarbonylalkyl, hydroxyalkyi, haloalkyi, haloalkoxyalkyi, alkoxyalkoxyalkyl, thioalkoxyalkoxyalkyi, (N-alkanoyl-N- alkyl)aminoalkyl, alkylsulfonylamidoalkyl, cycloalkyi, cycloalkylalkyl, aminocarbonylalkyl, alkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, aminocarbonylalkenyl, alkylaminocarbonylalkenyl, dialkylaminocarbonylalkenyl, hydroxyalkenyl, aryl, arylalkyi, aryloxyalkyl, arylalkoxyalkyi, heterocyclic, (heterocyclic)alkyl and ( R aa)( R bb) N " R cC wherein R aa is aryl or arylalkyi, R bb is hydrogen or alkanoyl and R cc is alkylene, or a salt thereof. 48. The compound according to Claim 47 wherein m is zero or 1 ; R5b is alkylene; Q is a leaving group; and W is -CO2-G wherein G is hydrogen or a carboxy protecting group; or the substantially pure (+)- or (-)-isomer thereof. 49. The compound according to Claim 47 wherein n and m are both 0; R5 is alkylene; Q is a leaving group; W is -CO2-G wherein G is hydrogen or a carboxy protecting group; and Ri is (i) Ioweralkyl, (ii) alkenyl, (iii) heterocyclic (alkyl), (iv) aryloxyalkyl, (v) arylalkyi, (vi) (N-alkanoyl-N-alkyl)aminoalkyl, (vii) alkylsulfonylamidoalkyl or (viii) substituted or unsubstituted 4- methoxyphenyl, 4-fluorophenyl, 3-fluorophenyl, 4-ethoxyphenyl, 4- ethylphenyl, 4-methylphenyl, 4-trifluoromethylphenyl, 4- pentafluoroethylphenyl, 3-fluoro-4-methoxyphenyl, 3-fluoro-4- ethoxyphenyl, 2-fluorophenyl, 4-methoxymethoxy phenyl, 4- hydroxyphenyl, 4-t-butylphenyl, 1 ,3-benzodioxolyl, 1 ,4-benzodioxanyl or dihydrobenzofuranyl wherein the substituent is selected from Ioweralkyl, haloalkyi, alkoxy, alkoxyalkoxy and carboxyalkoxy, and R is substituted or unsubstituted 1 ,3-benzodioxolyl, 7-methoxy-1 ,3- benzodioxolyl, 1 ,4-benzodioxanyl, 8-methoxy-1 ,4-benzodioxanyl, dihydrobenzofuranyl, benzofuranyl, 4-methoxyphenyl, dimethoxyphenyl, fluorophenyl or difluorophenyl wherein the substituent is selected from Ioweralkyl, alkoxy and halogen; or the substantially pure (+)- or (-)-isomer thereof. 50. The compound according to Claim 47 of the formula wherein n is 0 or 1 ; m is 0 to 6; R5 is alkylene; Q is a leaving group; W is (a) -C(0)2-G where G is hydrogen or a carboxy protecting group, (b) -PO3H2, (c) -P(0)(OH)E where E is hydrogen, Ioweralkyl or arylalkyi, (d) -CN, (e) -C(0)NHR17 where R17 is Ioweralkyl, (f) alkylaminocarbonyl, (g) dialkylaminocarbonyl, (h) tetrazolyl, (i) hydroxy, (j) alkoxy, (k) sulfonamido, (I) -C(0)NHS(0)2R16 where R16 is Ioweralkyl, haloalkyi, phenyl or dialkylamino, (m) -S(0)2NHC(0)Rl6. (n) -662- R l is selected from Ioweralkyl, alkenyl, haloalkyi, haloalkoxyalkyi, alkoxyalkoxyalkyl, cycloalkylalkyl, aryl, arylalkyi, aryloxyalkyl, (heterocyclic)alkyl, (N-alkanoyl-N-alkyl)aminoalkyl, and alkylsulfonylamidoalkyl, and R2 is selected from the group consisting of hydrogen, Ioweralkyl, alkenyl, alkynyl, alkoxyalkyi, alkoxycarbonylalkyl, hydroxyalkyi, haloalkyi, haloalkoxyalkyi, alkoxyalkoxyalkyl, thioalkoxyalkoxyalkyi, (N-alkanoyl-N- alkyl)aminoalkyl, alkylsulfonylamidoalkyl, cycloalkyi, cycloalkylalkyl, aminocarbonylalkyl, alkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, aminocarbonylalkenyl, alkylaminocarbonylalkenyl, dialkylaminocarbonylalkenyl, hydroxyalkenyl, aryl, arylalkyi, aryloxyalkyl, arylalkoxyalkyi, heterocyclic, (heterocyclic)alkyl and ( R aa)( R bb) N " R cc" wherein R aa is aryl or arylalkyi, R DD is hydrogen or alkanoyl and R cc is alkylene, or a salt thereof. 51 . The compound according to Claim 50 wherein m is zero or 1 ; R5 is alkylene; Q is a leaving group; and W is -CO2-G wherein G is hydrogen or a carboxy protecting group; or the substantially pure (+)- or (-)-isomer thereof. 52. The compound according to Claim 50 wherein n and m are both 0; R5b is alkylene; Q is a leaving group; W is -CO2-G wherein G is hydrogen or a carboxy protecting group; and Ri is (i) Ioweralkyl, (ii) alkenyl, (iii) heterocyclic (alkyl), (iv) aryloxyalkyl, (v) arylalkyi, (vi) (N-alkanoyl-N-alkyl)aminoalkyl, (vii) alkylsulfonylamidoalkyl or (viii) substituted or unsubstituted 4- methoxyphenyl, 4-fluorophenyl, 3-fluorophenyl, 4-ethoxyphenyl, 4- ethylphenyl, 4-methylphenyl, 4-trifluoromethylphenyl, 4- pentafluoroethylphenyl, 3-fluoro-4-methoxyphenyl, 3-fluoro-4- ethoxyphenyl, 2-fluorophenyl, 4-methoxymethoxyphenyl, 4- hydroxyphenyl, 4-t-butylphenyl, 1 ,3-benzodioxolyl, 1 ,4-benzodioxanyl or dihydrobenzofuranyl wherein the substituent is selected from Ioweralkyl, haloalkyi, alkoxy, alkoxyalkoxy and carboxyalkoxy, and R2 is substituted or unsubstituted 1 ,3-benzodioxolyl, 7-methoxy-1 ,3- benzodioxolyl, 1 ,4-benzodioxanyl, 8-methoxy-1 ,4-benzodioxanyl, dihydrobenzofuranyl, benzofuranyl, 4-methoxyphenyl, dimethoxyphenyl, fluorophenyl or difluorophenyl wherein the substituent is selected from Ioweralkyl, alkoxy and halogen; or the substantially pure (+)- or (-)-isomer thereof. 53. A compound of the formula wherein n is 0 or 1; m is 0 to 6; R5 is alkylene; R 20a ιs hydrogen, Ioweralkyl, alkenyl, haloalkyi, alkoxyalkyi, haloalkoxyalkyi, cycloalkyi, cycloalkylalkyl, aryl or arylalkyi; W is (a) -C(0)2-G where G is hydrogen or a carboxy protecting group, (b) -PO3H2, (c) -P(0)(OH)E where E is hydrogen, Ioweralkyl or arylalkyi, (d) -CN, (e) -C(0)NHR-|7 where R17 is Ioweralkyl, (f) alkylaminocarbonyl, (g) dialkylaminocarbonyl, (h) tetrazolyl, (i) hydroxy, (j) alkoxy, (k) sulfonamido, (I) -C(0)NHS(0)2R16 where R16 is Ioweralkyl, haloalkyl.phenyl or dialkylamino, (m) -S(0)2NHC(0)Rl6> R 1 is selected from Ioweralkyl, alkenyl, haloalkyi, haloalkoxyalkyi, alkoxyalkoxyalkyl, cycloalkylalkyl, aryl, arylalkyi, aryloxyalkyl, (heterocyclic)alkyl, (N-alkanoyl-N-alkyl)aminoalkyl, and alkylsulfonylamidoalkyl, and R2 is selected from the group consisting of hydrogen, Ioweralkyl, alkenyl, alkynyl, alkoxyalkyi, alkoxycarbonylalkyl, hydroxyalkyi, haloalkyi, haloalkoxyalkyi, alkoxyalkoxyalkyl, thioalkoxyalkoxyalkyi, (N-alkanoyl-N- alkyl)aminoalkyl, alkylsulfonylamidoalkyl, cycloalkyi, cycloalkylalkyl, aminocarbonylalkyl, alkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, aminocarbonylalkenyl, alkylaminocarbonylalkenyl, dialkylaminocarbonylalkenyl, hydroxyalkenyl, aryl, arylalkyi, aryloxyalkyl, arylalkoxyalkyi, heterocyclic, (heterocyclic)alkyl and ( R aa)( R bb) N_R cc" wherein R aa is aryl or arylalkyi, R b b is hydrogen or alkanoyl and R cc is alkylene, or a salt thereof. 54. The compound according to Claim 53 wherein m is zero or 1 ; R5 is alkylene; R 20a ιs hydrogen, Ioweralkyl, alkenyl, haloalkyi, alkoxyalkyi, haloalkoxyalkyi, cycloalkyi, cycloalkylalkyl, aryl or arylalkyi; and W is -CO2-G wherein G is hydrogen or a carboxy protecting group; or the substantially pure (+)- or (-)-isomer thereof. 55. The compound according to Claim 53 wherein n and m are both 0; R5b is alkylene; R 20a is hydrogen, Ioweralkyl, alkenyl, haloalkyi, alkoxyalkyi, haloalkoxyalkyi, cycloalkyi, cycloalkylalkyl, aryl or arylalkyi; W is -CO2-G wherein G is hydrogen or a carboxy protecting group; and Ri is (i) Ioweralkyl, (ii) alkenyl, (iii) heterocyclic (alkyl), (iv) aryloxyalkyl, (v) arylalkyi, (vi) (N-alkanoyl-N-alkyl)aminoalkyl, (vii) alkylsulfonylamidoalkyl or (viii) substituted or unsubstituted 4- methoxyphenyl, 4-fluorophenyl, 3-fluorophenyl, 4-ethoxyphenyl, 4- ethylphenyl, 4-methylphenyl, 4-trifluoromethylphenyl, 4- pentafluoroethylphenyl, 3-fluoro-4-methoxyphenyl, 3-fluoro-4- ethoxyphenyl, 2-fluorophenyl, 4-methoxymethoxyphenyl, 4- hydroxyphenyl, 4-t-butylphenyl, 1 ,3-benzodioxolyl, 1 ,4-benzodioxanyl or dihydrobenzofuranyl wherein the substituent is selected from Ioweralkyl, haloalkyi, alkoxy, alkoxyalkoxy and carboxyalkoxy, and R 2 is substituted or unsubstituted 1 ,3-benzodioxolyl, 7-methoxy-1 ,3- benzodioxolyl, 1 ,4-benzodioxanyl, 8-methoxy-1 ,4-benzodioxanyl, dihydrobenzofuranyl, benzofuranyl, 4-methoxyphenyl, dimethoxyphenyl, fluorophenyl or difluorophenyl wherein the substituent is selected from Ioweralkyl, alkoxy and halogen; or the substantially pure (+)- or (-)-isomer thereof. 56. The compound according to Claim 53 of the formula wherein n is 0 or 1 ; m is 0 to 6; R5b is alkylene; 20a ' s hydrogen, Ioweralkyl, alkenyl, haloalkyi, alkoxyalkyi, haloalkoxyalkyi, cycloalkyi, cycloalkylalkyl, aryl or arylalkyi; W is (a) -C(0)2-G where G is hydrogen or a carboxy protecting group, (b) -PO3H2, (c) -P(0)(OH)E where E is hydrogen, Ioweralkyl or arylalkyi, (d) -CN, (e) -C(0)NHRi7 where R17 is Ioweralkyl, (f) alkylaminocarbonyl, (g) dialkylaminocarbonyl, (h) tetrazolyl, (i) hydroxy, (j) alkoxy, (k) sulfonamido, (I) -C(0)NHS(0)2 16 where R16 is Ioweralkyl, haloalkyi, phenyl or dialkylamino, (m) -S(0)2NHC(0)Ri6, -668- Xf (r) (t) H , or R l is selected from Ioweralkyl, alkenyl, haloalkyi, haloalkoxyalkyi, alkoxyalkoxyalkyl, cycloalkylalkyl, aryl, arylalkyi, aryloxyalkyl, (heterocyclic)alkyl, (N-alkanoyl-N-alkyl)aminoalkyl, and alkylsulfonylamidoalkyl, and R2 is selected from the group consisting of hydrogen, Ioweralkyl, alkenyl, alkynyl, alkoxyalkyi, alkoxycarbonylalkyl, hydroxyalkyi, haloalkyi, haloalkoxyalkyi, alkoxyalkoxyalkyl, thioalkoxyalkoxyalkyi, (N-alkanoyl-N- alkyl)aminoalkyl, alkylsulfonylamidoalkyl, cycloalkyi, cycloalkylalkyl, aminocarbonylalkyl, alkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, aminocarbonylalkenyl, alkylaminocarbonylalkenyl, dialkylaminocarbonylalkenyl, hydroxyalkenyl, aryl, arylalkyi, aryloxyalkyl, arylalkoxyalkyi, heterocyclic, (heterocyclic)alkyl and (R aa )(Rbb) N " R cC wherein R aa is aryl or arylalkyi, Rbb is hydrogen or alkanoyl and R cc is alkylene, or a salt thereof. 57. The compound according to Claim 56 wherein m is zero or 1 ; R 5b is alkylene; R 20a ,s hydrogen, Ioweralkyl, alkenyl, haloalkyi, alkoxyalkyi, haloalkoxyalkyi, cycloalkyi, cycloalkylalkyl, aryl or arylalkyi; and W is -C02-G wherein G is hydrogen or a carboxy protecting group; or the substantially pure (+)- or (-)-isomer thereof. 58. The compound according to Claim 56 wherein n and m are both 0; R 5 b is alkylene; R 20a is hydrogen, Ioweralkyl, alkenyl, haloalkyi, alkoxyalkyi, haloalkoxyalkyi, cycloalkyi, cycloalkylalkyl, aryl or arylalkyi; W is -CO2-G wherein G is hydrogen or a carboxy protecting group; and Ri is (i) Ioweralkyl, (ii) alkenyl, (iii) heterocyclic (alkyl), (iv) aryloxyalkyl, (v) arylalkyi, (vi) (N-alkanoyl-N-alkyl)aminoalkyl, (vii) alkylsulfonylamidoalkyl or (viii) substituted or unsubstituted 4- methoxy phenyl, 4-fluorophenyl, 3-fluorophenyl, 4-ethoxyphenyl, 4- ethylphenyl, 4-methylphenyl, 4-trifluoromethylphenyl, 4-pentafluoroethylphenyl, 3-fluoro-4- methoxyphenyl, 3-fluoro-4-ethoxy phenyl, 2-fluorophenyl, 4-methoxymethoxyphenyl, 4-hydroxyphenyl, 4-t-butylphenyl, 1 ,3-benzodioxolyl, 1 ,4-benzodioxanyl or dihydrobenzofuranyl wherein the substituent is selected from Ioweralkyl, haloalkyi, alkoxy, alkoxyalkoxy and carboxyalkoxy, and R 2 is substituted or unsubstituted 1 ,3-benzodioxolyl, 7-methoxy-1 ,3- benzodioxolyl, 1 ,4-benzodioxanyl, 8-methoxy-1 ,4-benzodioxanyl, dihydrobenzofuranyl, benzofuranyl, 4-methoxyphenyl, dimethoxyphenyl, fluorophenyl or difluorophenyl wherein the substituent is selected from Ioweralkyl, alkoxy and halogen; or the substantially pure (+)- or (-)-isomer thereof. 59. A pharmaceutical composition for antagonizing endotheiin comprising a therapeutically effective amount of the compound of Claim 1 and a pharmaceutically acceptable carrier. 60. A pharmaceutical composition for antagonizing endotheiin comprising a therapeutically effective amount of the compound of Claim 21 and a pharmaceutically acceptable carrier. 61. A method for antagonizing endotheiin comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound of Claim 1. 62. A method for antagonizing endotheiin comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound of Claim 21. 63. A method for treating hypertension, congestive heart failure, restenosis following arterial injury, cerebral or myocardial ischemia or atherosclerosis comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound of Claim 1. 64. A method for treating coronary angina, cerebral vasospasm, acute and chronic renal failure, gastric ulceration, cyclosporin-induced nephrotoxicity, endotoxin-induced toxicity, asthma, LPL-related lipoprotein disorders, proliferative diseases, acute or chronic pulmonary hypertension, platelet aggregation, thrombosis, IL-2 mediated cardiotoxicity, nociception, colitis, vascular permeability disorders, ischemia-repurfusion injury, raynaud's disease and migraine comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound of claim 1. 65. A method for treating hypertension, congestive heart failure, restenosis following arterial injury, cerebral or myocardial ischemia or atherosclerosis comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound of Claim 21. 66. A method for treating coronary angina, cerebral vasospasm, acute and chronic renal failure, gastric ulceration, cyclosporin-induced nephrotoxicity, endotoxin-induced toxicity, asthma, LPL-related lipoprotein disorders, proliferative diseases, acute or chronic pulmonary hypertension, platelet aggregation, thrombosis, IL-2 mediated cardiotoxicity, nociception, colitis, vascular permeability disorders, ischemia-repurfusion injury, raynaud's disease and migraine comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound of claim 21. 67. A method for treating treating hypertension, congestive heart failure, restenosis following arterial injury, cerebral or myocardial ischemia or atherosclerosis comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound of Claim 1 in combination with one or more cardiovascular agents. 68. A method for treating treating hypertension, congestive heart failure, restenosis following arterial injury, cerebral or myocardial ischemia or atherosclerosis comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound of Claim 21 in combination with one or more cardiovascular agents. 69. A process for the preparation of a compound of the formula: wherein E is a carboxy-protecting group and Ri and R2 are independently selected from Ioweralkyl, alkenyl, alkoxyalkyi, alkoxycarbonylalkyl, hydroxyalkyi, haloalkyi, haloalkoxyalkyi, alkoxyalkoxyalkyl, thioalkoxyalkoxyalkyi, cycloalkyi, cycloalkylalkyl, aminocarbonylalkyl, alkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, aminocarbonylalkenyl, alkylaminocarbonylalkenyl, dialkylaminocarbonylalkenyl, aryl, arylalkyi, aryloxyalkyl, arylalkoxyalkyi, (N-alkanoyl-N-alkyl)aminoalkyl, alkylsulfonylamidoalkyl, heterocyclic and (heterocyclic)alkyl; or a salt thereof, comprising a) catalytic hydrogenation of a compound of the formula: wherein E, R- | and R 2 are defined as above and b) catalytic hydrogenation of the product of step a) in the presence of an acid or a mixture of acids. 70. The process of Claim 67 wherein the hydrogenation catalyst is Raney nickel and the acid is a mixture of acetic acid and trifluoroacetic acid. 71. The process of Claim 67 wherein E is Ioweralkyl and Ri and R2 are as described above. 72. A process for the preparation of a compound of the formula: wherein E is a carboxy-protecting group and Ri and R2 are independently selected from Ioweralkyl, alkenyl, alkoxyalkyi, alkoxycarbonylalkyl, hydroxyalkyi, haloalkyi, haloalkoxyalkyi, alkoxyalkoxyalkyl, thioalkoxyalkoxyalkyi, cycloalkyi, cycloalkylalkyl, aminocarbonylalkyl, alkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, aminocarbonylalkenyl, alkylaminocarbonylalkenyl, dialkylaminocarbonylalkenyl, aryl, arylalkyi, aryloxyalkyl, arylalkoxyalkyi, (N-alkanoyl-N-alkyl)aminoalkyl, alkylsulfonylamidoalkyl, heterocyclic and (heterocyclic)alkyl; or a salt thereof, comprising a) catalytic hydrogenation of a compound of the formula: wherein E, R- j and R2 are defined as above, b) catalytic hydrogenation of the product of step a) in the presence of an acid or a mixture of acids, and c) epimerization of the product of step b) with a base. 73. The process of Claim 70 wherein E is Ioweralkyl, R- j and R2 are as defined above. 74. The process of Claim 70 wherein the hydrogenation catalyst is Raney nickel and the acid is a mixture of acetic acid and trifluoroacetic acid. 75. A process for the preparation of a compound of the formula: wherein E is a carboxy-protecting group, Ri and R2 are independently selected from Ioweralkyl, alkenyl, alkoxyalkyi, alkoxycarbonylalkyl, hydroxyalkyi, haloalkyi, haloalkoxyalkyi, alkoxyalkoxyalkyl, thioalkoxyalkoxyalkyi, cycloalkyi, cycloalkylalkyl, aminocarbonylalkyl, alkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, aminocarbonylalkenyl, alkylaminocarbonylalkenyl, dialkylaminocarbonylalkenyl, aryl, arylalkyi, aryloxyalkyl, arylalkoxyalkyi, (N-alkanoyl-N-alkyl)aminoalkyl, alkylsulfonylamidoalkyl, heterocyclic and (heterocyclic)alkyl and R3 is R4-C(0)-R5- wherein R5 is alkylene and R4 is (R11)(R12)N- wherein R11 and R12 are independently selected from (1 ) Ioweralkyl, (2) haloalkyi, (3) alkoxyalkyi, (4) haloalkoxyalkyi, (5) alkenyl, (6) alkynyl, (7) cycloalkyi, (8) cycloalkylalkyl, (9) aryl, (10) heterocyclic, (1 1 ) arylalkyi, (13) hydroxyalkyi, ( 14) alkoxy, (15) aminoaikyl, (16) trialkylaminoalkyl, and (17) (heterocyclic)alkyl; or a salt thereof, comprising a) catalytic hydrogenation of a compound of the formula: wherein E, R- j and R are defined as above, b) catalytic hydrogenation of the product of step a) in the presence of an acid or a mixture of acids, c) epimerization of the product of step b) with a base and d) alkyation of the product of step c) with a compound of the formula R3-X wherein X is a leaving group and R3 is defined as above. 76. The process of Claim 73 wherein E is Ioweralkyl, R- j and R 2 are as defined above, and R3 is -CH2C(0)NRι ι R- | 2 wherein R- j - j and R- j 2 are independently selected from the group consisting of Ioweralkyl, aryl, hydroxyalkyi, alkoxy, aminoaikyl, trialkylaminoalkyl, and heterocyclic. 77. The process of Claim 73 wherein the hydrogenation catalyst is Raney nickel and the acid is a mixture of acetic acid and trifluoroacetic acid. 78. A process for the preparation of the substantially pure (+)- trans.trans optical isomer of the compound of the formula: wherein E is Ioweralkyl, Ri and R2 are independently selected from Ioweralkyl, alkenyl, alkoxyalkyi, alkoxycarbonylalkyl, hydroxyalkyi, haloalkyi, haloalkoxyalkyi, alkoxyalkoxyalkyl, thioalkoxyalkoxyalkyi, cycloalkyi, cycloalkylalkyl, aminocarbonylalkyl, alkylaminocarbonylalkyl, dialkylaminocarbonylalkyi, aminocarbonylalkenyl, alkylaminocarbonylalkenyl, dialkylaminocarbonylalkenyl, aryl, arylalkyi, aryloxyalkyl, arylalkoxyalkyi, (N-alkanoyl-N-alkyl)aminoalkyl, alkylsulfonylamidoalkyl, heterocyclic and (heterocyclic)alkyl, or a salt thereof, comprising reacting a mixture of the (+) and (-) enantiomers of the compound of the formula: with S-(+)- mandelic acid and separating the mandelate salt of the (+)- trans.trans optical isomer.

Inventors: BOYD STEVEN A, HENRY KENNETH J JR, HUTCHINS CHARLES W, JAE HWAN-SOO, KESTER JEFFREY A, KING STEVEN A, LIU GANG, SORENSEN BRYAN K, SZCZEPANKIEWICZ BRUCE G, TASKER ANDREW S, VON GELDERN THOMAS W, WINN MARTIN, WITTENBERGER STEVEN J, BOYD, STEVEN, A., HENRY, KENNETH, J., JR., HUTCHINS, CHARLES, W., JAE, HWAN-SOO, KESTER, JEFFREY, A., KING, STEVEN, A., LIU, GANG, SORENSEN, BRYAN, K., SZCZEPANKIEWICZ, BRUCE, G., TASKER, ANDREW, S., VON GELDERN, THOMAS, W., WINN, MARTIN, WITTENBERGER, STEVEN, J.
Applicants: ABBOTT LAB, ABBOTT LABORATORIES
Application year: 1997
Main classification: C07D405
IPC codes: A61K31, A61P1, A61P7, A61P9, A61P11, A61P13, A61P25, A61P43, C07D207, C07D211, C07D401, C07D403, C07D405, C07D409, C07D413, C07D417, C07D419, C07D453, C07D471, C07D491, C07F9