4-AMINO 6-SUBSTITUTED MYCOPHENOLIC ACID AND DERIVATIVES WITH IMMUNOSUPPRESSIVE ACTIVITY

Abstract: The disclosed derivatives of mycophenolic acid of formula (I) are therapeutic agents advantageous in the treatment of disease states indicated for mycophenolic acid and/or mycophenolate mofetil and other immunosuppressant agents.

Description: 4-AMINO 6-SUBSTITUTED MYCOPHENOLIC ACID AND DERIVATIVES WITH IM-MUNOSUPPRESSIVE ACTIVITY 5 Field of the Znvention The present invention relates to derivatives of mycophenolic acid in which the 4-hydroxy group has been replaced by 4-amino derivatives, and the 6-methoxy group has been replaced by other substituents. The invention includes natural and derivative side chains at the 5-position. The 10 invention is also directed to formulations and methods for treatment. Background Information and Related Disclosures Mycophenolic acid ("MPA") was initially described as a weakly-active antibiotic found in the fermentation broth of Penicillium breviccarpactum, having the following structure. Mycophenolic Acid MPA and certain related compounds, such as mycophenolate mofetil (the morpholinoethyl ester of MPA) , having the following structure: have more recently been described as having particularly advantageous properties as immunosuppreεεant drugs. Various derivatives of mycophenolic acid, their syntheεis and uses in the treatment of autoimmune disorders, psoriasis, inflammatory diseases, 35 including, in paruicular, rheumatoid arthritis, tumors, viruses, and for treatment of allograft rejection, are described in U.S. Patents Nos. 4,686,234; 4,725,622; 4,727,069; 4,748,173; 4,753,935; 4,786,637; 4,808,592; 4,861,776; 4,868,153; 4,948,793; 4,952,579; 4,959,387; 4,992,467; 5,247,083; and U.S. Patent Application Serial No. 07/927,260, 40 filed August 7, 1992. As immunoεuppressive agentε, the previously described eεterε and „ derivatives of mycophenolic acid are useful in treating auto-immune related diεorders, glomerulonephritiε and hepatitis, and in preventing allograft j \ rejection. As anti-inflammatory agents, they are useful in treating * 45 rheumatoid arthritis. As anti-tumor agents, they are useful in treating solid tu orε and malignancieε of lymphoreticular origins. See alεo U.S. Patentε No. 3,825,571 and 3,853,919; Japanese Pat. No. J 01290667; J. Med. Chem., 33(2), 833-8 (1990) ; Austr. J. Chem. , 31(2), 353-64, (1978) ; and J " . AntiJbiot. , 29(3), 275-85, 286-91 (1976) . The discloεed compounds are described as having anti-tumor, immunosuppressive, anti-viral, anti-arthritic and/or anti-psoriatic activities. The article by J. . Patterεon and G. Huang, Chemical Communications, 1579 (1991) describes synthetic methodology of interest with respect to such compounds. The above-cited patents, publications, and the references/ publications referenced therein, are all incorporated herein by reference. SUMMARY OF THE INVENTION Derivatives of mycophenolic acid and their esters and the pharmaceutically acceptable salts thereof, i.e. the compounds of Formula I: wherein: R 1 is hydrogen or lower alkyl; R 2 is hydrogen, lower alkyl, -C(0)R 3 , -C(0)NRR 5 , -C0 2 R 6 , or -S0 2 R 3 ; in which: R 3 iε hydrogen, lower alkyl, halo lower alkyl or optionally substituted phenyl; R 4 is hydrogen, lower alkyl or optionally εubεtituted phenyl; R 3 is hydrogen, lower alkyl or optionally εubεtituted phenyl; R 6 iε lower alkyl or optionally εubεtituted phenyl; and R 7 iε lower alkyl, cycloalkyl, fluorovinyl, difluorovinyl, trifluorovinyl, lower alkenyl, -C≡C-R 8 , allyl, CHO, or CH j OR 9 ; in which: R 8 iε hydrogen or lower alkyl, and R 9 iε hydrogen or 4-methoxybenzyl; and Z is a side chain selected from Formulae ZA, ZB, ZC, ZD, ZE, ZF, ZG, and ZH: Formula ZA wherein: Z 1 is hydrogen, lower alkyl, halo or CF 3 ; Z 2 iε hydrogen, lower alkyl, lower alkoxy, aryl, or -CHjZ 13 , where Z 13 is .aryl -*-" heteroaryl; Z 3 is hydrogen, lower alkyl, lower alkenyl, lower alkoxy, phenyl, or -S(0)-,Z 12 , where Z 12 is lower alkyl, and m is 0, 1 or 2; Z 4 is hydrogen, lower alkyl, or phenyl, or Z 3 and Z 4 taken together with the carbon to which they are attached form cycloalkyl of three to five carbon atoms; and G is OH, lower alkoxy, lower thioalkyl., -NG'G 2 , -OfCH^-NG'G 2 , or - 0(0- 2 .-N=G 3 , where n is an integer from 1 to 6, G 1 is hydrogen or lower alkyl, G 2 is hydrogen or lower alkyl, and =G 3 is lower alkylene of four to six carbon atoms, or lower alkylene of three to five carbon atoms pluε one member that iε -0-, -S-, or -N(G 4 ) - where G 4 is hydrogen or lower alkyl; Formula ZB wherein: Z 5 iε hydrogen or lower alkyl; Z 8 iε hydrogen or lower alkyl; D 1 and D 2 together with their adjacent carbon atomε form an optionally εubεtituted, εaturated or unεaturated carbocyclic or heterocyclic ring of 3 to 7 atomε; and G is as defined above; or Formula ZC wherein: Z 3 , Z 8 , and G are as defined above; or Formula ZD wherein: D 3 iε -CHj- or -CHjCHj-; and G is as defined above; or Formula ZE wherein: Z 6 iε hydrogen, lower alkyl, lower alkoxy, -COOH, -NHj or halo; Z 7 iε hydrogen, lower alkyl, lower alkoxy or halo; and Z 5 and G are aε defined above; or Formula ZF wherein: Z 1 and G are as defined above; or Formula ZG wherein: D 3 , Z 2 , Z 3 , Z 4 and G are as defined above; or Formula ZH wherein: D 4 is -CH--, -CHjCHj-, -CΑJZH-CX^- , -0-, or -OCHj-; and Z 1 and G are as defined above; and the pharmaceutically acceptable salts thereof. In another aspect, the invention relates to a pharmaceutical composition containing a therpeutically effective amount of a compound of Formula I or a pharmaceutically acceptable salt thereof admixed with at leaεt one pharmaceutically acceptable excipient. In still another aspect, the invention relates to a method of treating immune, inflammatory, tumor, proliferative, viral and psoriatic diεorderε in a mammal by ad iniεtering to a mammal in need of εuch treatment a therapeutically effective amount of a compound of Formula I or a pharmaceutically acceptable salt thereof. DETAILED DESCRIPTION OF THE INVENTION Definitions and General Parameters The "following definitions are set forth to illustrate and define the meaning and scope of the various termε used to describe the invention herein. As used herein, the term "alkyl" refers to a fully εaturated monovalent radical of one to twelve carbon atomε containing only carbon an hydrogen, and which may be a cyclic, branched or straight chain radical. This term iε further exemplified by radicalε such as methyl, ethyl, t-butyl, pentyl, cyclopentyl, cyclohexyl, heptyl, cycloheptyl and adamantyl. The term "lower alkyl" referε to a monovalent alkyl radical of one to six carbon atoms. This term iε further exemplified by such radicalε as methyl, ethyl, n-propyl, isopropyl, cyclopropyl, n-butyl, t-butyl, i-butyl (or 2-methylpropyl) , isoamyl, pentyl, cyclopentyl, i-pentyl, hexyl and cyclohexyl. The term "lower alkenyl" referε to an unsaturated monovalent hydrocarbon radical of one to six carbon atoms. This term is further exemplified by such radicals as vinyl, prop-2-enyl, pent-3-enyl, and hex-5-enyl. The term "halo" refers to fluoro and chloro, unleεε otherwise specified. The term "halo lower alkyl" referε to a lower alkyl radical εubεtituted with one or more chlorine or fluorine atomε. This term iε further exemplified by such radicals aε trichloromethyl, trifluoromethyl, dichloromethyl, fluoromethyl, difluoro-chloro-methyl, 3-chloropropyl and 4-trifluoro-2-chloro-butyl. The term "halomethyl" refers to a methyl radical substituted with one or more chlorine and/or fluorine atomε. This term is further exemplified by such radicals as trichloromethyl, trifluoromethyl, dichloromethyl, fluoromethyl and difluorochloromethyl. The term "lower alkylene" referε to a divalent alkyl radical of one to εix carbon atomε. This term is further exemplified by such radicals aε methylene, ethylene, n-propylene, i-propylene, n-butylene, t-butylene, i-butylene (or 2-methylpropylene) , iεoamylene, pentylene, and n-hexylene. The term "alkoxy" meanε the group -OR wherein R is lower alkyl. The term "lower alkanol" means an alcohol of the formula ROH where R is a lower alkyl. This term iε further exemplified by εuch alcoholε aε methanol, ethanol, n-propanol, i-propanol, n-butanol, t-butanol, i-butanol (or 2-methylpropanol) , pentanol, n-hexanol. The moiety "-N=G 3 " as defined represents a heterocycle radical εuch aε pyrrolidino, piperidino, hexamethyleneimino, imidazolidino, thiazolidino, morpholino, thiomorpholino, piperazino, thiopentamethyleneimino, and the like. The term "optionally εubεtituted phenyl" referε to phenyl and mono-, di-, or tri-εubstituted phenyl, wherein the optional subεtituentε are lower alkyl, lower alkoxy, hydroxy, trifluoromethyl, or halo. Thiε term iε further exemplified by εuch radicalε aε 2-chlorophenyl, 2- trifluoromethylphenyl, 4-methoxyphenyl, 4-chlorophenyl, 3,4- dimethoxyphenyl, 2-chloro-3,4-dimethoxyphenyl, 4-hydroxyphenyl, 4-methylphenyl, 3-1-butylphenyl, and 4-hexylphenyl. The term "aryl" referε to a monovalent unsaturated aromatic carbocyclic radical having a single ring (e.g., phenyl) or two condensed rings (e.g., naphthyl), which can optionally be mono-, di- or tri-εubεtituted, independently, with OH, COOH, lower alkyl, lower alkoxy, chloro, fluoro, trifluoromethyl and/or cyano. The term "heteroaryl" referε to a monovalent aromatic carbocyclic radical having at leaεt one heteroatom, εuch as N, O or S, within the ring, such aε quinolyl, benzofuranyl, pyridyl, morpholinyl and indolyl, which can optionally be mono-, di- or tri-substituted, independently, with OH, COOH, lower alkyl, lower alkoxy, chloro, fluoro, trifluoromethyl and/or cyano. The term "optionally εubεtituted, saturated or unsaturated carbocyclic or heterocyclic ring of 3 to 7 atoms" aε used with reference to a side chain of Formula ZB encompases side chains of the following structures: where the line inside each respective ring indicates the optional presence of a double bond and X 1 , X 2 , X 3 , X 4 and X 5 can independently be -CHX*-, -C(O)-, -C(N-X b )-, -C(N-NX d X β ) -, -0-, -S-, -S(O)-, -S(0) 2 - or -NX C -, where X* iε hydrogen, lower alkyl or forms a double bond; X is acyl, carbamoyl or ureido; X c is lower alkyl, C(0)X d , StOjX" or CfOJN ^; and X* 1 and X° are independently hydrogen or lower alkyl; provided that if more than one heteroatom is present such heteroatoms are separated by at least one carbon atom. Thus, a sidechain of Formula ZB in which D 1 and D 2 together represent -CH 2 CH 2 CH 2 CH 2 - , and Z 5 and Z 8 are both hydrogen, would be named as a 2- [(2-ethylidene) -2-cyclohex-l-yl]acetic acid derivative. Likewise, a sidechain of Formula ZB in which D 1 and D 2 together represent -CHxCRflCR,- , and Z 3 and Z 8 are both hydrogen, would be named aε a 2- [ (2-ethylidene) -4-tetrahydropyran-3-yl]acetic acid derivative. The term "optional" or "optionally" means that the subsequently described event or circumstance may or may not occur, and that the deεcription includeε instances in which said event or circumstance occurs and instances in which it does not. For example, "optionally substituted phenyl" means that the phenyl may or may not be εubεtituted and that the deεcription includeε both unεubεtituted phenyl and phenyl wherein there iε substitution: "optionally" followed by "converting the free base to the acid addition salt" means that such conversion may or may not be carried out in order for the process described to fall within the invention, and the invention includes those processeε wherein the free base iε converted to the acid addition salt and thoεe proceεεeε in which it is not. A "pharmaceutically acceptable salt" may be any salt derived from an inorganic or organic acid or base. Salts may be derived from acids or baεeε. The acid addition salts are derived from inorganic acids, εuch as hydrochloric acid, hydrobromic acid, sulfuric acid (giving the sulfate and biεulfate salts) , nitric acid, phosphoric acid and the like, and organic acidε such as acetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, malic acid, malonic acid, εuccinic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid,, ethaneεulfonic acid, salicylic acid, p-toluenesulfonic acid, and the like. The base addition εaltε are derived from inorganic bases εuch as sodium hydroxide, potassium hydroxide, lithium hydroxide, ammonia, calcium hydroxide, magnesium hydroxide and the like. Cations derived from organic bases include those formed from primary, secondary and tertiary amines, such aε iεopropylamine, diethylamine, trimethylamine, triethylamine, pyridine, cyclohexylamine, ethylene diamine, monoethanolamine, diethanolamine, triethanolamine, and the like. Aε uεed herein, the term "inert organic εolvent" or "inert εolvent" means a εolvent inert under the conditionε of the reaction being deεcribed in conjunction therewith (including, for example, benzene, toluene, acetonitrile, tetrahydrofuran, diethyl ether, chloroform, methylene chloride, pyridine, xylene, dimethylformamide, 1,4-dioxane, dichloromethane, and the like) . As used herein, the term "treatment" or "treating" eanε any treatment of a disease in a mammal, and includes: (i) preventing the diεeaεe, that is, causing the clinical symptomε of the diεeaεe not to develop; (ii) inhibiting the diεease, that is, arresting the development of clinical εymptomε; and/or (iii) relieving the diεeaεe, that is, causing the regresεion of clinical symptoms. As uεed herein, the term "effective amount" means a dosage sufficient to provide treatment. This will vary depending on the patient and the treatment being effected. "Iεomers" are different compounds that have the same molecular formula. "Stereoisomers" are iεomers that differ only in the way the atoms are arranged in space. "Enantiomerε" are a pair of εtereoiεomerε that are non-εuperimposable mirror images of each other. A 1:1 mixture of a pair of enantiomerε iε a "racemic" mixture. The term " (±) " is used to designate a racemic mixture where appropriate. "Diaεtereoiεomerε" are εtereoiεomerε that have at least two asymmetric atoms, but which are not mirror-imageε of each other. The abεolute εtereochemistry iε εpecified according to the Cahn-Ingold-Prelog R-S system. When the compound iε a pure enantiomer the stereochemistry at each chiral carbon may be specified by either R or S. Resolved compounds whose absolute configuration is unknown are designated (+) or (-) depending on the direction (dextro- or laevorotary) which they rotate the plane of polarized light at the wavelength of the sodium D line. When a compound iε a racemic mixture the εtereochemiεtry at each chiral carbon may be specified by either RS or SR by reference to a single enantiomer of the racemate. In this manner relative εtereochemistry is conveyed unambiguouεly. The compoundε of the invention may possess one or more asymmetric centers, and can be produced as a racemic mixture or as individual enantiomerε or diastereoisomers. The number of stereoisomers present in any given compound of Formula I depends upon the number of asymmetric centers present (there are 2" stereoisomers possible where n is the number of asymmetric centerε) . The individual stereoisomers may be obtained by resolving a racemic or non-racemic mixture of an intermediate at some appropriate stage of the synthesis, or by resolution of the compound of Formula I by conventional means. The individual stereoisomers (including individual enantiomers and diastereoisomers) aε well aε racemic and non-racemic mixtureε of εtereoisomers are encompaεsed within the scope of the present invention, all of which are intended to be depicted by the structures of this specification unless otherwise specifically indicated. Specific examples of the separation of iεomerε are set forth in the Examples. Unless specified to the contrary, the reactions described herein take place at atmoεpheric preεεure over a temperature range from about -20°C to about 100°C, more preferably from about 10°C to about 50°C, and most preferably at about room temperature. Isolation and purification of the compounds and intermediates described herein can be effected, if desired, by any suitable separation or purification procedure such as, for example, filtration, extraction, crystallization, column chromatography, thin-layer chromatography or thick-layer chromatography, or a combination of these procedures. Specific illustrations of suitable separation and isolation procedures can be found by reference to the exampleε hereinbelow. However, other equivalent separation or isolation procedures can, of course, also be used. Nomenclature The compoundε of Formula I will be named uεing the numbering εyεtem illuεtrated below. The iεobenzofuranyl nucleuε of the compoundε of Formula I iε numbered as follows: 28000-FF -10- Following are exampleε of how some representative compounds of Formula I are named. Sidechains of Formula ZA are numbered aε shown below: Representative compounds of Formula I where the εidechain is ZA are as follows: and are named: 1. (E) -6- (4-amino-l,3-dihydro-6,7-dimethyl-3-oxoisobenzofuran-5-yl) - 2 (S) ,4-dimethyl-4-hexenoic acid; 2. (E) -6- (6-cyclopropyl-l,3-dihydro-7-methyl-3-oxo-4- trifluoroacetylaminoiεobenzofuran-5-yl) -2 (S) -ethyl-4-methyl-4- hexenoic acid; 3. methyl (E) -6- (1,3-dihydro-7-methyl-4-methylamino-3-oxo-6- vinyliεobenzofuran-5-yl) -3-hydroxy-2-methylεulfonylamino-2-phenyl-4- trifluoromethyl-4-hexenoate; 4. thiomethyl (E) -4-chloro-6- (l,3-dihydro-4- (3,3-dimethylureido) -6- ethynyl-7-methyl-3-oxoiεobenzofuran-5-yl) -3-methyl-2-methylεulfonyl- 4-hexenoate. Sidechainε of Formula ZB in which D 1 and D 2 do not contain a hetero atom are numbered aε εhown below: Representative compounds of Formula I where the εidechain is ZB in which D 2 does not include a hetero atom are aε followε: and are named: 1. (E) -2-{2- [2- [l,3-dihydro-4-amino-6-hydroxymethyl-7-methyl-3- oxoiεobenzofuran-5-yl]ethylidene] cyclopent-1- (S) -yl}acetic acid; 2. (E) -2-{2- [2- (l,3-dihydro-6- (2-fluorovinyl) -7-methyl-4-methylamino-3- oxoiεobenzofuran-5-yl)ethylidene] cyclohex-1-yl}acetic acid; 3. (E) -2-{2- [2- (l,3-dihydro-7-methyl-3-oxo-6- (prop-2-enyl) -4- trifluoroacetylaminoisobenzofuran-5-yl)ethylidene] cyclohept-l- yljpropionic acid dimethylamide (where G 1 and G 2 are both methyl) ; 4. thiomethyl (E) -2-{2- [2- (6- (but-2-ynyl) -l,3-dihydro-4- (3,3- dimethylureido) -7-methyl-3-oxoisobenzofuran-5-yl)ethylidene] - cyclobut-1- (R) -yl}αctanoate. Sidechains of Formula ZB that include a heteroatom are numbered differently, depending upon the position of the heteroato (s) in the ring. For example, a sidechain of Formula ZB in which D 1 and D 2 together with their adjacent carbon atoms form a saturated heterocyclic ring of 6 atoms is numbered as shown below: where D represents -0-, -S(0), -N(R 9 ) and the like. Representative compounds of Formula I where the sidechain is ZB including a hetero atom are as followε: and are named: 1. (E) -2-{4- [2- (4-amino-1,3-dihydro-6,7-dimethyl-3-oxoiεobenzofuran-5- yl)ethylidene] tetrahydrofuran-3-yl}acetic acid; 2. hexyl (E) -2-{4- [2- (1,3-dihydro-6-formyl-7-methyl-3-oxo-4- trifluoroacetylaminoiεobenzofuran-5-yl)ethylidene] -3-methylpiperidin- 3 (S) -yljpropionate; 3. (E) -2-{4- [2- (1,3-dihydro-6-ethyl-7-methyl-4-methylamino-3- oxoiεobenzofuran-5-yl)ethylidene] thiepan-3-yl}heptanoic acid dimethylamide (where G 1 and G 2 are both methyl) . Sidechainε of Formula ZC are numbered as shown below: Representative compoundε of Formula I where the εidechain iε ZC are as followε: where MB = 4-methoxybenzyl and are named: 1. 3- (4-amino-l,3-dihydro-6,7-dimethyl-3-oxoisobenzofuran-5-ylmethyl) -2- methylcyclopent-2-enyl-l- (S) -acetic acid; hexyl 3- (1,3-dihydro-6- (4-methoxybenzyloxymethyl) -7-methyl-3-oxo-4- trifluoroacetylaminoiεobenzofuran-5-ylmethyl) cyclopent-2-enyl-1- acetate; 2- (S) - [3- (6-cyclohexyl-l,3-dihydro-7-methyl-4-methylamino-3- oxoisobenzofuran-5-ylmethyl) -2-methylcyclopent-2-en-l(S) -yl] -3- methylbutyric acid; 2-dimethylaminoethyl 3- (4-amino-l,3-dihydro-7-methyl-3-oxo-6- propylisobenzofuran-5-ylmethyl) -2-hexylcyclopent-2-en-l-ylacetate (where G 1 and G 2 are both methyl) . Sidechains of Formula ZD are numbered as shown below: w h e r e D ' i s C H . w h e r e D i s C H _, C H - Representative compounds of Formula I where the sidechain is ZD are as follows: and are named: 1. (E) -3- [2- (4-amino-l,3-dihydro-6,7-dimethyl-3-oxoisobenzofuran-5- yl)ethylidene] cyclopentane-1- (R) -carboxylic acid; 2. hexyl (E) -4- [2- (1,3-dihydro-6-ethyl-7-methyl-3-oxo-4- trifluoroacetylaminoiεobenzofuran-5-yl)ethylidene] cyclohexane-1- carboxylate; 3. methyl (E) -3- [2- (l,3-dihydro-7-methyl-4-methylamino-3-oxo-6- trifluorovinyliεobenzofuran-5-yl)ethylidene] cyclopentane-1- thiocarboxylate. Sidechains of Formula ZE are numbered aε shown below: Representative compounds of Formula I where the sidechain is ZE are as follows: and are named: 1. (E) -2- [3- (4-amino-l,3-dihydro-6,7-dimethyl-3-oxoiεobenzofuran-5-yl) - 1- ethylprop-1-en-1-yl]benzoic acid; 2. (E) -2- [3- (6-εec-butyl-l,3-dihydro-7-methyl-3-oxo-4- trifluoroacetylaminoiεobenzofuran-5-yl)prop-1-en-1-yl] -6- methylbenzoic acid dimethylamide (where G 1 and G 2 are both methyl) ; 3. hexyl (E) -6-chloro-2- [3- (6-allyl-l,3-dihydro-7-methyl-4-methylamino- 3-oxoisobenzofuran-5-yl) -1-hexylprop-l-en-l-yl] -4-methoxybenzoate. Sidechainε of Formula ZF are numbered aε shown below: Representative compoundε of Formula I where the εidechain is ZF are aε followε: and are named: 1. 4 - (4 -amino- 1 , 3 -dihydro- 6 , 7 -dimethyl -3 -oxoiεobenzofuran- 5 -ylmethyl) -3 - methylcyclopent-3 -ene-l- (S) -carboxylic acid; 2 . ethyl 4 - (l , 3 -dihydro-6-ethyl-7 -methyl-3 -oxo-4 - trifluoroacetylaminoiεobenzofuran-5-ylmethyl) -3-hexylcyclopent-3-ene- 1-carboxylate; 3. thiomethyl 4- (6-cyclopentyl-l,3-dihydro-7-methyl-4-methylamino-3- oxoisobenzofuran-5-ylmethyl)cyclopen -3-ene-1-carboxylate. Sidechains of Formula ZG are numbered as shown below: Repreεentative compounds of Formula I where the sidechain is ZG are as follows: and are named: 1. 3- [3- (S) - (4-amino-l,3-dihydro-6,7-dimethyl-3-oxoisobenzo-furan-5- yl) cyclopent-1-en-l-yl] -propionic acid; 2. 3- [3- (l,3-dihydro-6-ethyl-7-methyl-4-methylamino-3-oxo-isobenzofuran- 5-yl) cyclopent-1-en-l-yl] -2,3-dimethyl- -phenyl propionic acid. Sidechainε of Formula ZH are numbered as shown below: Representative compoundε of Formula I where the εidechain iε ZH are as follows: are named as follows: 1. (E) -2- [3- (4-amino-1,3-dihydro-6,7-dimethyl-3-oxoisobenzofuran-5-yl) - 1-methylprop-l-en-l-yl] cyclopentane-1-carboxylic acid; 2. Ethyl (E) -2- [3- (l,3-dihydro-6-ethyl-7-methyl-3-oxo-4- trifluoroacetylaminoisobenzofuran-5-yl) -1-methylpro -1-en-1- yl] cyclohexane-1R-carboxylate; 3. Thiomethyl (E) -2- [3- (l,3-dihydro-6-methoxymethyl-7-methyl-4- methylamino-3-oxoiεobenzofuran-5-yl)prop-l-en-l-yl] cycloheptane-1- carboxylate. Compoundε of Formula I where the side chain iε ZH, in which D 4 iε a heteroatom, are numbered differently, in that the heteroatom iε designated aε poεition 1 of the ring. For example, the compound where D 4 is oxygen, and R 1 and R 2 are both hydrogen, R 7 is methyl, Z 1 iε methyl, and G iε hydroxy, iε named as follows: (E) -2- [3- (4-amino-l,3-dihydro-6,7-dimethyl-3-oxoisobenzofuran-5-yl) - 1-methylprop-l-en-l-y ]furan-3-carboxylic acid. PREPARATION OF COMPOUNDS OF FORMULA I The compounds of Formula I are prepared from the lower alkyl 4- iεocyanato..eεterε of Formula 6, the εtructure of which iε shown below: Formu la 6 where Z* iε a sidechain of Formula Z as defined in the Summary of the Invention in which G iε lower alkoxy. The compounds of Formula 6 are prepared from intermediates of Formula A: Formula A where Z* iε as defined above. The preparation of compoundε of Formula A is illustrated below in Reaction Scheme XXIII. The compounds of Formula 6 are then converted to the compoundε of Formula I by εeveral different εynthetic pathwayε, depending on the desired subεtitutions at the 4-position. Many of the eεterification routeε and/or final esteri ication steps for the eεterε of the 4-εubεtituted derivatives of mycophenolic acid are described in U.S. Patent Nos. 4,686,234; 4,725,622; 4,727,069; 4,748,173; 4,753,935; 4,861,776; and the pending application entitled "Direct Esterification of Mycophenolic Acid", Serial No. 07/911635, filed July 10, 1992 (by inventors working in the same research organization as that of the preεent applicantε, and subject to an obligation of assignment to the same aεsignee as in the present application) all previously incorporated herein by reference. By substituting the acids of Formula I for mycophenolic acid or its acid derivatives aε deεcribed in the above references, the esterification routes and/or final steps described may likewise be used. Starting Materials The intermediates of Formula A are prepared starting from compoundε of Formula 1, the εtructure of which iε shown below: Formul 1 where Z* iε aε defined above. The compoundε of Formula 1 may be prepared aε deεcribed below in Reaction Schemeε I to XXII. The preparation of εuch compoundε is also described in more detail in co-pending Application Serial No. 08/???,???, Attorney Docket No. DO-MPA-1, entitled "???"; filed contemporaneously herewith, which iε hereby incorporated by reference in itε entirety. Aε those skilled in the art will appreciate, the intermediates synthesized in the preparation of compoundε of Formula 1, e.g., where R* iε toεyl and/or where G iε lower alkoxy can be εubεtituted in Reaction Scheme XXIII for the compoundε of Formula 1 and B without need for conversion through corresponding compounds where R* iε H and G is OH. For example, the compounds of Formula 105 where R* is aryl or alkylsulfonyl can be uεed directly aε compound of Formula 2 in Reaction Scheme XXIII. Alternatively, when R 7 iε lower alkyl or cycloalkyl, by using mycophenolic acid as the starting material and performing the syntheses described with reference to Reaction Schemeε XXIII and XXIV, the correεpondingly obtained 6-substituted derivatives can be further derivatized at the 4- and/or 5-position(ε) , e.g., as described with reference to Reaction Schemes I through XXII. Starting Materials Mycophenolic acid is commercially available, e.g., from Sigma Chemical Company, St. Louis, MO. The mycophenolic acid lower alkyl eεterε of Formula 1 can be εyntheεized, for example, aε deεcribed in Synthetic Organic Chemiεtry by Wagner and Zook (Wiley, New York) 1956, εee pageε 479- 532. Other reactantε, εuch aε methoxyethoxy methyl chloride, t-butyl- dimethylεilyl chloride, and various orthoesters are likewiεe commercially available or may be readily prepared by thoεe εkilled in the art uεing commonly employed synthetic methodology. Preparation of Compounds of Formula 1 where Z is Sidechain ZA One ftiethod of preparing compounds of Formula 1 where Z is the sidechain of Formula ZA, illustrated as compoundε of Formula 1A, is shown below in Reaction Schemes I to X. REACTION SCHEME I Formula 101 Formula 102 Fo lkyl Formula 104a Formula 1A aε on ester Preparation of Formula 102 As illustrated in Reaction Scheme I, Step 1, the , phenolic hydroxyl group of a mycophenolic acid lower alkyl ester is protected. A mycophenolic acid lower alkyl ester of Formula 101, in a solvent (such as ether, ethyl acetate, dimethyformamide, or preferably dichloromethane) , is reacted with an equimolar amount of a halogenated protecting group (εuch as: methoxyethoxymethyl chloride; a sulfonyl chloride, e.g., tosyl chloride, mesyl chloride; or a εilyl chloride, e.g., trimethylεilyl chloride, diphenylmethyl ilyl chloride, or preferably tert-butyldimethylεilyl chloride) in presence of an equimolar amount of an organic base (εuch as diiεopropylethylamine, triethylamine or imidazole) . The reaction takes place at -20 to 35°C (preferably at 25°C) for 1 to 24 hours (preferably 16 hours) to give the correεponding compound of Formula 102 (where R* iε the protecting group) . Preparation of Formula 103 As illustrated in Reaction Scheme I, Step 2, the side chain double bond of a protected mycophenolic acid lower alkyl ester is ozonized to yield an aldehyde. A stream of ozonized oxygen is pasεed through a εolution of a protected compound of Formula 102 in a solvent (εuch as an alcohol, a halocarbon, or preferably a mixture of methanol and dichloromethane) . The reaction takes place at -100 to -40°C (preferably at -80°C) , and continues until the presence of excesε ozone iε detected by the development of a blue color. The reεultant hydroperoxide reduced without further purification, by the addition of a reducing agent (such as zinc and acetic acid, dimethyl sulfide, or preferably thiourea) . The reaction takeε place at -80°C to 25°C (preferably 0°C) over a period of 12 to 24 hourε (preferably 16 hours), to give the corresponding aldehyde of Formula 103. Preparation of Formula 104 As illustrated in Reaction Scheme I, Step 3, the aldehyde is converted to a carbinol by addition of an organometallic compound of Formula 103a [where M is MgBr or lithium, preferably MgBr (a Grignard reagent) ; Z 1 iε hydrogen, lower alkyl or CF 3 , and Z 2 is hydrogen or lower alkyl] . An organolithium reagent is formed by reaction of a halovinyl (preferably bromovinyl) compound of Formula 103a (where M is halo) with an alkyllithium (preferably n-butyllithium) in an ethereal εolvent (εuch as ether, or preferably tetrahydrofuran) . The reaction takeε place at -100 to 0°C (preferably -40°C) over a period of 0.5 to 5 hourε (preferably 1 hour) . Alternatively the halovinyl compound of Formula 103a is reacted with magnesium metal in an ethereal solvent (εuch aε ether or preferably tetrahydrofuran) . The reaction takes place at 30 to 60°C (preferably 40°C) over a period of 1 to 6 hours (preferably 2 hourε) . The organometallic compound of Formula 103a where M iε zinc or cadmium may be prepared by reaction of 103a where M is Li or MgBr with a zinc or cadmium halide, preferably chloride. The compound of Formula 103a where M iε tin may be prepared by reaction of 103a where M iε Li or MgBr with a trialkyl chloroεtannane, preferably tributyltin chloride. The compound of Formula 103a where M iε tin may alεo be prepared by reaction of 103a where M iε trifluoromethanesulfonate by reaction with a compound of formula (R 3 Sn),, where R iε alkyl, preferably methyl, in the preεence of a palladium catalyst, preferably tetrakiε(triphenylphoεphine) alladium. The compound of Formula 103a where M iε trifluoromethaneεulfonate may be prepared from a ketone of the formula: by reaction with a εtrong baεe (εuch aε εodium hydride or potaεsium hexamethyldisilazide) , followed by reaction of the anion thus produced with tri luoromethaneεulfonic anhydride. Alternatively, the compound of Formula 103a where M iε tin may be prepared by reacting a trialkyl tin hydride (preferably tributyl tin hydride) with an acetylene of the formula Z'-C≡C-Z 2 . One molar equivalent of the resultant organometallic reagent is added to a solution of an aldehyde of Formula 103 (in the same solvent system used to make the organometallic reagent) . The reaction takeε place at -80 to 20°C .(preferably 0 β C) over a period of 5 to 60 minuteε (preferably 10 minutes) to give the corresponding carbinol of Formula 104. Preparation of Formula 105 As illustrated in Reaction Scheme I, Step 4, an alkyl ester of Formula 105 is formed by a Claisen ortho ester rearrangement reaction of a carbinol of Formula 104 and an orthoester of Formula 104a (where Z 3 iε hydrogen, halo, lower alkyl, lower alkenyl, phenyl, alkoxy or -thio lower alkyl; and Z 4 iε hydrogen or lower alkyl; or Z 3 and Z 4 taken together with the carbon to which they are attached form cycloalkyl) . A carbinol of Formula 104 iε heated at 50 to 140°C (preferably about 130°C) with about 10 molar equivalentε of an orthoester of Formula 104a, in the presence of from 0.05 to 0.25 molar equivalents (preferably 0.10 molar equivalents) of an organic acid catalyst (εuch aε propionic, butyric, or preferably trimethylacetic acid) . The reaction takes place over a period of 1 to 48 hourε (preferably 3 hours) to give the corresponding alkyl ester of Formula 105. Preparation of Formula 1A Compoundε of Formula 1A are prepared as eεterε by deprotection of compoundε of Formula 105 aε described below with reference to Reaction Scheme X, -'Step 1; they are hydrolyzed to the correεponding carboxylic acid aε deεcribed below with reference to Reaction Scheme X, Step 2. Preparation of Enantiomers of Formula 1A where Z 2 is Lower Alkyl One method of preparing individual enantiomerε of compounds of Formula 1A iε from chiral compounds of Formula 104b, the preparation of which is shown below in Reaction Scheme II. REACTION SCHEME II Formula 103 Formu la 103f Formula 103g where Y iε chloro or bromo. Formula 103g Formula 103a For mu la 103h Formula 104b Preparation of Formula 103f Aε illuεtrated in Reaction Scheme II, Step 1, an aldehyde of Formula 103 is oxidized to the correεponding carboxylic acid of Formula 103f. An aldehyde of Formula 103 iε reacted with about two molar equivalentε of an oxidizing agent (for example, chromic acid, silver oxide, bleach, or preferably εodium periodate) , in an inert εolvent (εuch as toluene, or preferably ethyl acetate) , in the presence of water and a catalytic amount (for example, about 0.01 molar equivalents) of a catalyst (εuch aε ruthenium oxide, or preferably ruthenium trichloride) . The reaction takeε place at 0 to 40°C (preferably 25°C) for 30 minuteε to 8 hours (preferably 2 hours) , to give the correεponding carboxylic acid of Formula 103f. Preparation of Formula 103g Aε illustrated in Reaction Scheme II, Step 2, a carboxylic acid of Foiπnula 103f is converted to the corresponding acyl halide of Formula 103g. A carboxylic acid of Formula 103f is reacted with about one molar equivalent, preferably 1.1 molar equivalents, of a halogenating agent (for example, thionyl chloride, thionyl bromide, or preferably oxalyl chloride) , in an inert solvent (such aε dichloromethane, or preferably ethyl acetate) , in the presence of a catalytic amount (for example, about 0.05 molar equivalents) of dimethylformamide. The reaction takes place at 0 to 40°C (preferably 25°C) for 30 minutes to 8 hourε (preferably 2 hours) , to give the corresponding acyl halide of Formula 103g. Preparation of Formula 103h Aε illuεtrated in Reaction Scheme II, Step 3, an acyl halide of Formula 103g iε converted to the corresponding keto olefin of Formula 103h by addition of an organometallic compound of Formula 103a. An acyl halide of Formula 103g is reacted with about one molar equivalent of a organometallic compound of Formula 103a (where M iε cadmium, zinc, tin, or the like, prepared aε εhown in the preparation of compounds of Formula 104) , in an inert solvent (such as dichloromethane, ether, or preferably tetrahydrofuran) , optionally in the presence of a catalytic amount (for example, about 0.05 molar equivalents) of a palladium catalyst [preferably tetrakis (triphenylphosphine)palladium] . The reaction takeε place at -10 to 20°C (preferably 0°C) for 30 minutes to 8 hourε (preferably 4 hourε) , to give the correεponding keto olefin of Formula 103h. Preparation of Formula 104b Aε illuεtrated in Reaction Scheme II, Step 4, a keto olefin of Formula 103h is reduced εtereospecifically to the corresponding carbinol of Formula 104b by reduction with borane methyl εulfide in the preεence of a catalytic amount of (R) -tetrahydro-l-methyl-3,3-diphenyl-lH,3H-pyrrolo- [1,2-c] [1,3,2]oxazaborole. A keto olefin of Formula 103h iε sterospecifically reduced with about one molar equivalent of borane methyl εulfide in the preεence of a catalytic amount (0.05-0.3 molar equivalentε) of (R) -tetrahydro-1-methyl- 3,3-diphenyl-lH,3H-pyrrolo- [1,2-c] [1,3,2] oxazaborole in an inert solvent (preferably a mixture of toluene and dichloromethane) . The reaction takes place at -30 to 40°C (preferably -20°C) for 1-24 hourε (preferably 12 hourε) , to give the correεponding carbinol of Formula 104b. Preparation of Enantiomers of Compounds of Formula 1A The chiral carbinol of Formula 104b is then converted to an enantiomer of a compound of Formula 1A in the same manner aε εhown above in Reaction Scheme I (converεion of compoundε of Formula 104 to 105 to 1A) . Preparation of Compounds of Formula 1A where Z 2 is Hydroxy Compounds of Formula 1A where Z 2 iε hydroxy are prepared aε εhown below in Reaction Scheme III. REACTION SCHEME III Formula 103b For lkyl Formula 106a Preparation of Formula 106 Aε illustrated in Reaction Scheme III, Step 1, an aldehyde of Formula 103 iε tranεformed into an unεaturated aldehyde of Formula 106 by a Wittig reaction with an ylid of Formula 103b (where Z 1 iε hydrogen or lower alkyl) . An aldehyde of Formula 103 iε reacted with one molar equivalent of an ylid of Formula 103b, in an organic solvent (such aε dichloromethane, dimethylformamide or preferably toluene) . The reaction takeε place at 0 to 110°C (preferably 80°C) for 1 to 24 hourε (preferably 8 hourε) to give the correεponding unεaturated aldehyde of Formula 106. Preparation of Formula 107 Aε illustrated in Reaction Scheme III, Step 2, an unsaturated aldehyde of Formula 106 is condensed with the anion of an ester of Formula 106a (where Z 3 is hydrogen, lower alkyl, lower alkenyl, or phenyl and Z 4 is hydrogen, lower alkyl, or phenyl) to give a beta-hydroxy ester of Formula 107. An ester of Formula 106a iε converted to an alkali metal εalt by reacting a εolution of the eεter in an ethereal solvent (such as ether or preferably tetrahydrofuran) with an equimolar amount of an alkali metal hydride, hexamethyldisilazide or amide (preferably lithium diiεopropylamide) at a temperature of -100 to 0°C (preferably -80°C) , for 30 minutes to 2 hourε (preferably 30 minutes) to give a εolution of the correεponding ester anion. The ester anion εolution (1.0 to 1.5 molar equivalentε, preferably 1.0 molar equivalentε) iε added to a εolution of an unsaturated aldehyde of Formula 106 in the same ethereal solvent. The condensation reaction takes place at a temperature of -100°C to 0°C (preferably -80°C) for 1 to 6 hours (preferably 2 hours) to give the corresponding beta-hydroxy ester of Formula 107. Preparation of Compounds of Formula 1A where Z 2 is Alkoxy Compoundε of Formula 1A where Z 2 iε alkoxy are prepared as shown below in Reaction Scheme IV. REACTION SCHEME IV Formu la 07 Formu la 108 Preparation of Formula 108 As illustrated in Reaction Scheme IV, Step 1, the beta-hydroxy group of an ester of Formula 107 iε O-alkylated to give the correεponding beta- alkoxy eεter (R b ) of Formula 108. An eεter of Formula 107 iε reacted with 1 to 3 (preferably 1.5) molar equivalentε of an alkyl halide (preferably an alkyl iodide, εuch aε methyl iodide or n-butyl iodide, preferably methyl iodide) and 1 to 3 (preferably 1.25) molar equivalentε of silver oxide, in a polar organic εolvent (εuch aε dioxane', dimethylformamide or preferably acetonitrile) . The reaction takeε place at 25 to 100°C (preferably 70°C) for 1 to 24 hours (preferably 4 hours) to give the corresponding beta-alkoxy ester of Formula 108. Preparation of Compounds of Formula 1A where Z 4 is Hydroxy Compounds of Formula 1A where Z 4 is hydroxy are prepared as shown below in Reaction Scheme V. REACTION SCHEME V Formu la 105 Formula A Preparation of Formula 1A where Z 4 is Hydroxy As illustrated in Reaction Scheme V, Step 1, an alpha-halo alkyl ester of Formula 105 (where Z 1 is hydrogen, lower alkyl or CF 3 , Z 2 iε hydrogen or lower alkyl, Z 3 iε hydrogen, lower alkyl, lower alkenyl, or phenyl, and Z 4 iε halo) iε converted to an alpha-hydroxy acid of Formula 1A where Z 4 iε hydroxy. The reaction takeε place by hydrolyεiε of an alpha- alkanoyloxy ester intermediate, formed by diεplacement of the alpha-halo group with an alkali metal alkanoate. An alpha-halo (preferably chloro) eεter of Formula 105 is reacted with 1 to 5 (preferably 3) molar equivalents of an alkali metal alkanoate (the metal preferably potasεium and the alkanoate preferably acetate) in a polar organic solvent (such as acetonitrile or preferably dimethylformamide) The reaction takes place at 40 to 100°C (preferably 75°C) for 1 to 24 hours (preferably 12 hourε) to give the corresponding alpha-alkanoyloxy ester intermediate (not εhown) , which iε employed without iεolation or further purification. The alpha-alkanoyloxy ester is then subjected to basic hydrolyεiε by reaction with 1 to 5 (preferably 2) molar equivalentε of an alkali metal hydroxide (preferably εodium hydroxide) in a mixture of water and an organic solvent (εuch aε methanol, dimethoxyethane or preferably tetrahydrofuran) . The reaction takeε place at 0 to 60°C (preferably 40°C) for 1 to 12 hours (preferably 4 hourε) , to afford the correεponding alpha- hydroxy acid of Formula 1A. Aε illuεtrated in Reaction Scheme V, when R* of Formula 105 iε a εilyl protecting group, the hydrolysis conditions are also effective for deprotection to restore the phenolic hydroxyl group. Alternatively, for example when R" is methoxymethylethyl, the deprotection and hydrolysiε procedureε deεcribed with reference to Reaction Scheme X, can be employed. Preparation of Chiral Compounds of Formula 1A One method of preparing chiral compounds of Formula 1A is shown below in Reaction Scheme VT. REACTION SCHEME VT Formula 109a Fo mu I a 1A Preparation of Formula 109 Aε illustrated in Reaction Scheme VI, Step 1, an unsaturated aldehyde of Formula 106 is reduced and then converted to the corresponding compound of Formula 109 in which R b is a leaving group (a sulfonate or halide, preferably a bromide) . An unsaturated aldehyde of Formula 106 iε reacted with from 0.5 to 2 (preferably 1) molar equivalentε of a reducing agent (such aε εodium cyanoborohydride or preferably sodium borohydride) in an alcoholic solvent (such aε ethanol, iεopropanol or preferably methanol) . The reaction takes place at 0 to 50°C (preferably 25°C) for 1 to 12 hours (preferably 2 hourε) to give the correεponding allylic alcohol (not εhown) which iε uεed without isolation or further purification. The allylic alcohol iε reacted with from 1 to 1.5 (preferably 1.25) molar equivalentε of a sulfonating agent (such aε p-tolueneεulfonyl chloride) and an organic base, or preferably reacted with a halogenating reagent (such aε carbon tetrachloride/triphenylphoεphine or preferably N-bromoεuccinimide/triphenylphoεphine) in an inert organic εolvent (εuch aε ether or preferably dichloromethane) . The reaction takeε place at a temperature of -40 to 40°C (preferably -10°C) for 1 to 12 hours (preferably 2 hours) to afford the corresponding compound of Formula 109. Preparation of Formula 110 As illustrated in Reaction Scheme VI, Step 2, an allylic halide or sulfonate of Formula 109 is alkylated with a chiral 4-alkyl N-acyl oxazolidinone of Formula 109a to give the correεponding chiral εubεtituted acyl oxazolidinone of Formula 110. An alkali metal (preferably lithium) εalt of a chiral 4-alkyl N-acyl oxazolidinone of Formula 109a (the alkyl group preferably being 4- iεopropyl) by reaction of the N-acyl oxazolidinone with 1 to 1.25 (preferably 1.05) molar equivalentε of an alkali metal hydride, hexamethyldisilazide or dialkylamide (preferably lithium diisopropylamide) in an inert organic εolvent (εuch aε ether or preferably tetrahydrofuran) . The reaction takes place at -100 to -20°C (preferably -80°C) for 5 to 120 minutes (preferably 30 minutes) . The εolution of the salt (1 to 1.5, preferably 1.25 molar equivalents) iε then added to a εolution of an allylic compound of Formula 109 in the same solvent. The alkylation reaction takeε place at -100 to 0°C (preferably -80°C) for 30 minuteε to 6 hours (preferably 1 hour) to afford the correεponding chiral substituted acyl oxazolidinone of Formula 110. Preparation of Chiral Formula IA As illustrated in Reaction Scheme VI, Step 3, a chiral substituted acyl oxazolidinone of Formula 110 iε hydrolyzed to the correεponding chiral acid of Formula 1A. Use of an acyl oxazolidinone of Formula 109a having a 4-alkyl subεtituent of the oppoεite configuration in Reaction Scheme VT, Step 2, followed by hydrolyεis as described in Step 3 resultε in the correεponding chiral acid where Z 3 haε the opposite configuration. An acyl oxazolidinone of Formula 110 is reacted with from 1.25 to 3.5 (preferably 3.0) molar equivalents of lithium hydroxide, in a mixture of water and a water-miscible organic solvent (such aε dioxane or preferably tetrahydrofuran) containing from 6 to 10 (preferably 8) molar equivalents of 30% aqueous hydrogen peroxide. The reaction takeε place at -20 to 40°C (preferably 20°C) for 1 to 24 hourε (preferably 12 hourε) to afford the correεponding chiral acid of Formula IA. Alternative Preparation of Compounds of Formula IA An alternative preparation of compounds of Formula IA is shown below in Reaction Scheme VII. REACTION SCHEME VII Formula 109 l I Formula 112 F Fnorrmmiui Il:a 109b Preparation of Formula 112 Aε illuεtrated in Reaction Scheme VII, Step 1, an allylic compound of Formula 109 in which R b is a leaving group (a sulfonate or halide, preferably a bromide) is condensed with an ester of Formula 109b to give the mono- or di-alkyl ester of Formula 112 (where Z 3 is hydrogen, lower alkyl, lower alkenyl, or phenyl and Z 4 is hydrogen, lower alkyl, or phenyl) . An eεter of Formula 109b iε converted to an alkali metal εalt by reaction with 1.05 to 1.25 (preferably 1.1) molar equivalentε of an alkali metal amide (εuch as sodium hexamethyldisilazide, potassium tetramethylpiperidide or preferably lithium diiεopropylamide) in an organic εolvent (εuch as ether, dioxane or preferably tetrahydrofuran) . The reaction takes place at -40 to 30°C (preferably 0°C) for 15 minutes to 3 hours (preferably 30 minutes) . Without isolation or further purification, the resulting solution of the alkali metal salt of the ester of Formula 109b (1.2 to 1.6, preferably about 1.3 molar equivalents) is then reacted with an allylic compound of Formula 109, in the same solvent, optionally in the presence of from 2% to 10% (preferably about 5%) by volume of hexamethyl phosphoric triamide. The reaction takeε place at -100 to -40°C (preferably -80°C) for 30 minutes to 6 hours (preferably 1 hour) to afford the corresponding alkyl ester of Formula 112. Preparation of Formula IA Compound of Formula IA are then obtained aε eεters by deprotection of compounds of Formula 105 as described below with reference to Reaction Scheme X, Step 1; they are hydrolyzed to the corresponding carboxylic acid as described below with reference to Reaction Scheme X, Step 2. Preparation of Compounds of Formula IA where Z 3 is S(θ) m alkyl Compounds of Formula IA where Z 3 is S(0) m alkyl are prepared as shown below in Reaction Scheme VTII. REACTION SCHEME VIII Formula 1A where Z' is SCC π ,alky Preparation of Formula IA where Z 3 is S(θ) m alkyl As illustrated in Reaction Scheme VIII, Step 1, a 2- (alkylthio) -4- hexenoic acid ester of Formula IA (where Z 3 is S-lower alkyl, and Z 4 iε hydrogen or lower alkyl) is oxidized to give the corresponding 2- (alkylsulfinyl) - or 2- (alkylsulfonyl) -4-hexenoic acid ester of Formula IA where Z 3 is S(O) lower alkyl or S(0) 2 lower alkyl. Alternatively, the reaction can be performed with an acid of Formula IA where Z 3 is S-lower alkyl, to give the correεponding acid where Z 3 iε 2- (alkylεulfinyl) or 2- (alkylsulfonyl) . An alkylthio-4-hexenoic acid eεter of Formula IA is reacted with 1.0 to 1.25 (preferably 1.05) molar equivalents of an oxidizing agent (such as oxone ® ) optionally in the presence of an inert support (such aε alumina) , in a solvent (such aε chloroform or preferably dichloromethane) . The reaction takeε place at 0 to 55°C (preferably 35°C) for 1 to 10 hours (preferably 2 hours) to afford the corresponding 2- (alkylsulfinyl) -4- hexenoic acid ester of Formula IA where Z 3 iε S (O) lower alkyl. By repeating the foregoing procedure under the same conditions [starting with the 2- (alkylsulfinyl) -4-hexenoic acid ester so-produced] , or by conducting the reaction with the 2- (alkylthio) -4-hexenoic acid ester starting material [and using 2.0 to 2.5 (preferably 2.25) molar equivalentε of oxone] the correεponding 2-alkylεulfonyl-4-hexenoic acid eεterε are produced. A 2- (alkylεulfinyl) - or 2- (alkylsulfonyl) -4-hexenoic acid ester of Formula I-ZA-K is hydrolyzed to give the corresponding acid as described with reference to Reaction Scheme X, Step 2. Preparation of Compounds of Formula IA where Z 1 is Halo Compounds of Formula IA where Z 1 is halo are prepared as shown below in Reaction Scheme IX. REACTION SCHEME IX Formula 103c Formula 114 Formula 115 Formu Ia 106b Formula 1A where Z is halo Preparation of Formula 114 Aε illuεtrated in Reaction Scheme IX, Step 1, a protected aldehyde of Formula 103 and a triphenylphosphoranylideneacetate of Formula 103c are combined in a Wittig reaction to give the correεponding alkyl-2-halo- butenoate eεter of Formula 114. An aldehyde of Formula 103 is reacted with 1.0 to 1.5 (preferably 1.1) molar equivalents of an alkyl 2-halo-2-triphenylphosphoranylidene- acetate of Formula 103c (the halo group preferably being chloro) in an organic solvent (such as acetonitrile, or preferably toluene) . The reaction takes place at 50 to 120°C (preferably 110°C) for 4 to 48 hourε (preferably 24 hours) to afford the corresponding alkyl 2-halo-4-aryl-2- butenoate ester of Formula 114. Preparation of Formula 115 As illustrated in Reaction Scheme IX, Step 2, a protected alkyl 2- halo-4-aryl-2-butenoate ester of Formula 114 is converted to the correεponding bromide of Formula 115 after reduction to the correεponding alcohol (not εhown) . A 2-halo-4-aryl-2-butenoate ester of Formula 114 (preferably a t- butyl ester) iε converted to the correεponding acid (preferably by dissolution in trifluoroacetic acid at room temperature for 1 to 2 hourε) . The acid. iε iεolated and purified by conventional meanε, then reacted with 0.5 to 3 (preferably 1.6) molar equivalentε of a reducing agent (εuch aε εodium cyanoborohydride, εodium borohydride, or preferably borane dimethyl diεulfide complex) in an inert solvent (such aε methanol, ethanol, iεopropanol or preferably THF) . The reaction takeε place at 0 to 50°C (preferably 25°C) for 1 to 48 hours (preferably 24 hours) to give the corresponding alcohol (not shown) which is used after purification. The c lylic alcohol so-produced is reacted with from 1 to 1.5 (preferably 1.25) molar equivalents of a εulfonating agent (such as p-toluenesulfonyl chloride) and an organic base, or preferably reacted with a halogenating reagent (such as carbon tetrachloride/triphenylphosphine or preferably N-bromosuccinimide/triphenylphosphine) in an inert organic solvent (εuch aε ether or preferably dichloromethane) . The reaction takeε place at a temperature of -40 to 40°C (preferably -10°C) for l to 12 hourε (preferably 2 hourε) to afford the correεponding 2-halo-4-aryl-2-butenyl bromide compound of Formula 115. Preparation of Formula IA where Z 1 is Halo Aε illuεtrated in Reaction Scheme IX, Step 3, a protected 2-halo-4- aryl-2-butenyl bromide compound of Formula 115 iε condenεed with a dialkyl malonate of Formula 116, εubεtituted by Z 4 (where Z 4 is hydrogen, lower alkyl, or phenyl) , which is hydrolysed and decarboxylated to give the corresponding 4-halo-4-hexenoic acid derivative of Formula IA where Z 1 is halo. An ester of Formula 116 (where Z 4 iε hydrogen, lower alkyl, or phenyl) iε converted to an alkali metal εalt by reaction with 1.05 to 1.25 (preferably 1.1) molar equivalentε of an alkali metal hydride (preferably sodium hydride) in an organic solvent (εuch aε ether, dioxane or preferably tetrahydrofuran) . The reaction takeε place at -40 to 30°C (preferably 0°C) for 15 minutes to 3 hours (preferably 30 minutes) . Without isolation or further purification, the resulting solution of the alkali metal salt of the ester of Formula 106b (1.2 to 1.6, preferably about 1.3 molar equivalents) iε then reacted with an allylic bromo compound of Formula 115 in the same solvent. The reaction takes place at -20 to 50°C (preferably 25°C) for 30 minutes to 6 hours (preferably 2 hours) to afford the correεponding dialkyl eεter derivative. The dialkyl ester thus produced iε then hydrolyεed conventionally, using a strong base, preferably aqueous εodium hydroxide, in a protic solvent, preferably ethanol, heating to reflux. The dicarboxylic acid thus produced iε separated conventionally, and then decarboxylated by heating, preferably in a high-boiling inert εolvent, moεt preferably 1,2- dichlorobenzene, to give the correεponding 4-halo-4-hexenoic acid derivative of Formula IA where Z 1 is halo. Preparation of Compounds of Formula IA Compoundε of Formula IA aε esters and carboxylic acids are obtained by deprotection and hydrolysiε aε shown below in Reaction Scheme X. REACTION SCHEME X lkyl Formula 117 For u la 1A as an ester Formula 1A as an acid Preparation of Formula IA as an Ester Aε illuεtrated in Reaction Scheme X, Step 1, a protected phenol of Formula 117 (which can be any of the corresponding protected compounds of Reaction Schemes I to IX, such aε Formulae 105, 107, 108, 112, and the like) iε deprotected to give the correεponding alkyl eεter of Formula IA aε an ester. An alkyl ester of Formula 117 (having either an acetal-type or a silyl-type protecting group) is treated with from 0.05 to 0.2 molar equivalentε (preferably 0.1 molar equivalentε) of an aqueouε mineral acid (such as sulfuric, perchloric, or preferably hydrochloric acid) , in a water-miscible organic solvent (such as methanol, acetone, or preferably ethanol) . The reaction takes place at 0 to 50°C (preferably 25°C) over a period bf 1 to 6 hours (preferably 2 hourε) to give the correεponding free phenol of Formula IA. Alternatively, to remove acetal-type protecting groups (such as MEM) a compound of Formula 117 is treated with 0.05 to 0.25 molar equivalents (preferably 0.1 molar equivalents) of a Lewis acid (such as zinc chloride or preferably zinc bromide) , in a solvent (such as benzene, chloroform, or preferably dichloromethane) . The reaction takeε place at 0 to 50°C (preferably 25°C) over a period of 1 to 12 hourε (preferably 3 hourε) to give the correεponding free phenol of Formula IA. Alternatively, to remove silyl-type protecting groupε (εuch aε t- butyldimethylsilyl) a compound of Formula 117 iε reacted with 1.0 to 1.5 (preferably 1.25) moles of a tetraalkyl ammonium fluoride (preferably tetrabutylammonium fluoride) in an ethereal solvent (such as dioxane or preferably tetrahydrofuran) . The reaction takeε place at -10 to 25°C (preferably 0°C) over a period of 0.1 to 2 hourε (preferably 0.5 hourε) to give the correεponding free phenol of Formula IA. Preparation of Formula IA as a Carboxylic Acid Aε illuεtrated in Reaction Scheme X, Step 2, a compound of Formula 1A aε an eεter (prepared aε described above) iε hydrolyzed to give the correεponding acid of Formula IA aε a carboxylic acid. An alkyl ester of Formula IA is reacted with from 1.5 to 4 molar equivalents (preferably 2 molar equivalents) of an inorganic hydroxide (such as potasεium, εodium, or preferably lithium hydroxide) in a mixture of water and an organic solvent (εuch as tetrahydrofuran, methanol, or preferably dimethoxyethane) . The reaction takes place at 0 to 60°C (preferably 40°C) over a period of 1 to 12 hourε (preferably 3 hourε) . The resulting anion is acidified with an aqueous mineral acid (εuch aε hydrochloric acid) . The acidification takes place at 0 to 40°C (preferably 25°C) over a period of 1 to 10 minutes (preferably 2 minutes) to give the corresponding carboxylic acid of Formula IA. Preparation of Compounds of Formula IB One method of preparing compounds of Formula 1 where Z is a sidechain of Formula ZB, illuεtrated aε compoundε of Formula IB, iε εhown below in Reaction Schemeε XI and XII. REACTION SCHEME XI Formu la 103 For ula 201 For u la 202 where M is Li or MgBr. For u la 202 Formu la 203 Formu la 203 Formula 1B Preparation of Formula 202 Aε illuεtrated in Reaction Scheme XI, Step 1, the aldehyde of Formula 103 iε converted to a carbinol of Formula 202 by addition of an unεaturated cyclic organometallic compound of Formula 201 where M iε Li or MgBr, prepared for example aε described above with reference to Reaction Scheme I, Step 3. One molar equivalent of the organometallic reagent 201 is added to a solution of an aldehyde of Formula 103 (in the εame εolvent εystem used to make the organometallic reagent) . The reaction takes place at -80 to -20°C (preferably -40°C) over a period of 5 to 60 minutes (preferably 15 minutes) to give the corresponding carbinol of Formula 202. Resolution of Formula 202 The racemic compound of Formula 202 may be separated into its two enantiomers by conventional meanε, for example by converεion into two diaεtereoiεomerε that are then εeparated by cryεtallization, chromatography, or by any conventional εeparation technique. Preferably, the carbinol iε reacted with a chiral isocyanate to give a mixture of diastereoisomeric carbamateε, which are separated by chromatography and cleaved to give the pure enantiomerε. A carbinol of Formula 202 is heated at 30 to 100°C (preferably about 60°C) with 2 to 6 molar equivalents (preferably 4 molar equivalents) of a chiral isocyanate in the presence of 1 to 1.5 molar equivalents (preferably 1.2 molar equivalents) of a strong organic base, for example 4-dimethylaminopyridine, in a hindered tertiary amine (for example diisopropylethylamine) as a solvent. The reaction takeε place over a period of 1 to 24 hours (preferably 7 hourε) to give the correεponding carbamate aε a mixture of diaεtereoiεomerε. The mixture of diaεtereoiεomeric carbamateε iε εeparated by conventional meanε, preferably chromatography. The individual diaεtereoiεomers are then separately cleaved by treatment with 1 to 1.5 molar equivalents (preferably 1.2 molar equivalents) of a trihalosilane, for example trichlorosilane, in the preεence of an exceεε of a tertiary amine, for example triethylamine, in an inert εolvent, for example toluene. The reaction takeε place at a temperature of 90-120°C (preferably 110°C) over a period of 5 minuteε to 2 hourε (preferably 15 minuteε) to give the correεponding enantiomer of the carbinol of Formula 202. Preparation of Formula 203 Aε illuεtrated in Reaction Scheme XI, Step 2, an alkyl ester of Formula 203 is formed by a Claisen ortho ester reaction of a carbinol of Formula 201 (or an enantiomer thereof) with an appropriately substituted orthoester. A carbinol of Formula 202 is heated at 50 to 140°C (preferably 130°C) with a large excesε of an orthoester of Formula 104a (see Reaction Scheme I, step 4), in the preεence of from 0.05 to 0.25 molar equivalents (preferably 0.10 molar equivalents) of an organic acid catalyst (such as propionic, butyric, or trimethylacetic acid, preferably trimethylacetic acid) . The reaction takeε place over a period of 1 to 24 hourε (preferably 2.5 hourε) to give the correεponding alkyl ester of Formula 203. Preparation of Formula IB Compounds of Formula IB are prepared as described with reference to Reaction Scheme X, Step 1 (deprotection to afford the corresponding alkyl ester of Formula IB) , and Step 2 (hydrolysiε to afford the correεponding acid of Formula IB) . Alternative Preparation of Enantiomers of Compounds of Formula IB Another method of preparing individual enantiomerε of compoundε of Formula 1 where Z iε sidechain ZB, illuεtrated aε compounds of Formula IB, is from chiral compounds of Formula 202b, the preparation of which is shown below in Reaction Scheme XII. REACTION SCHEME XII Formula 103g + D Fo Formu la 202a Formu la 202a Formu la 202b Preparation of Formula 202a Compoundε of Formula 202a are prepared aε described above with reference to Reaction Scheme II, Step 3 (conversion of 103g to 103h) . Preparation of Formula 202b Compounds of Formula 202b are prepared as described above with reference to Reaction Scheme II, Step 4 (converεion of 103h to 104b) . Preparation of Enantiomers of Compounds of Formula IB The chiral carbinol of Formula 202b iε then converted to an enantiomer of a compound of Formula IB in the εame manner aε εhown above in Reaction Scheme XI (converεion of compoundε of Formula 202 to 203 to IB) . Preparation of Compounds of Formula IC One method of preparing compounds of Formula l where Z iε a εidechain of Formula ZC, illuεtrated aε compoundε of Formula IC, is shown below in Reaction Scheme XIII. REACTION SCHEME XIII Formu In 302 Formu la 301 -37- Formula 302 For mu I a 303 15 Formu la 304 20 Formu la 304 Formu la 305 Formu la 306 Formula 307 40 45 Formula 308 Formu la 308 Formu la 309 Formula 1C Preparation of Formula 302 As illustrated in Reaction Scheme XIII, Step 1, an aldehyde of Formula 103 (prepared, for example aε deεcribed above with reference to Reaction Scheme I, Steps l and 2) iε tranεformed into an unεaturated aldehyde of Formula 302 by a Wittig reaction with an ylid of Formula 301 (where Z s iε hydrogen or lower alkyl) . An aldehyde of Formula 103 iε reacted with one molar equivalent of an ylid of Formula 301, in an organic εolvent (εuch aε dichloromethane, dimethylformamide or preferably toluene) . The reaction takeε place at 0 to 110°C (preferably 80°C) for 1 to 24 hourε (preferably 8 hourε) to give the corresponding unsaturated aldehyde of Formula 302. Preparation of Formula 303 Aε illuεtrated in Reaction Scheme XIII, Step 2, an unεaturated aldehyde of Formula 302 iε converted to the correεponding vinyl carbinol of Formula 303. An aldehyde of Formula 302 iε reacted with from 1.0 to 1.25 (preferably 1.1) molar equivalents of an organovinyl compound (preferably vinylmagnesium bromide) in a εolvent (εuch aε ether or preferably tetrahydrofuran) . The reaction takeε place at -30 to 20°C (preferably at 0°C) for 0.1 to 4 hours (preferably 0.5 hours) to give the correεponding vinyl carbinol of Formula 303. Preparation of Formula 304 As illustrated in Reaction Scheme XIII, Step 3, a vinyl carbinol of Formula 303 is oxidized to give the corresponding dienone of Formula 304. A vinyl carbinol of Formula 303 is reacted with 1.0 to 1.5 (preferably 1.1) molar equivalents of an oxidizing agent (εuch as manganese dioxide, pyridinium chlorochromate or preferably pyridinium dichromate) in a solvent (such as pyridine or preferably dichloromethane) . The reaction takes place at 0 to 30°C (preferably 25°C) for 30 minutes to 4 hourε (preferably 1 hour) to give the corresponding dienone of Formula 304. Preparation of Formula 305 As illuεtrated in Reaction Scheme XIII, Step 4, a dienone of Formula 304 iε cyclized to give the correεponding cyclopentenone of Formula 305. A dienone of Formula 304 reacted with 0.3 to 1.5 (preferably 1.0) molar equivalentε of a Lewiε acid (εuch aε boron trichloride, tin (IV) chloride or preferably boron trifluoride etherate) in a εolvent (εuch as tetrachloroethane or preferably dichloromethane) . The reaction takeε place at 0 to 30°C (preferably 25°C) for 1 to 6 hourε (preferably 2 hourε) to give the correεponding cyclopentenone of Formula 305. Preparation of Formula 306 Aε illuεtrated in Reaction Scheme XIII, Step 5, a cyclopentenone of Formula 305 iε reduced to give the corresponding cyclopentenol of Formula 306. A cyclopentenone of Formula 305 iε reacted with 1.0 to 1.5 (preferably- 1.1) molar equivalentε of a reducing agent (εuch aε lithium tri-tert-butoxyaluminium hydride or preferably sodium borohydride in the presence of an equimolar amount of cerium trichloride) in a mixture of an ethereal εolvent (preferably tetrahydrofuran) and a lower alkanol (preferably methanol) . The reaction takeε place at 0 to 40°C (preferably at 25°C) for 1 to 6 hourε (preferably 2 hourε) to give the cyclopentenol of Formula 306. Preparation of Formula 307 Aε illuεtrated in Reaction Scheme XIII, Step 6, a cyclopentenol of Formula 306 is tranεformed to the corresponding vinyl ether of Formula 307. A cyclopentenol of Formula 306 iε reacted with from 10 to 100 (preferably 50) molar equivalentε of a 1-alkenyl ether, optionally in the preεence of a co-εolvent (εuch aε ether or tetrahydrofuran) , in the preεence of from 0.1 to 0.5 (preferably 0.3) molar equivalentε of a mercury (II) εalt (preferably mercury (II) acetate) . The reaction takeε place at 0 to 50°C (preferably 25°C) for l to 5 days (preferably 2 days) to give the corresponding vinyl ether of Formula 307. Preparation of Formula 308 Aε illuεtrated in Reaction Scheme XIII, Step 7, a vinyl ether of Formula 307 iε rearranged to the correεponding acetaldehyde of Formula 308. A vinyl ether of Formula 307 iε reacted with from 10 to 100 (preferably 50) molar equivalents of a lithium εalt (εuch aε the tetrafluoroborate or preferably the perchlorate) in a solvent (such aε tetrahydrofuran or preferably ether) . The reaction takeε place at 0 to 35°C (preferably 25°C) for 0.1 to 2 hours (preferably 0.5 hours) to give the correεponding acetaldehyde of Formula 308. Preparation of Formula 309 Aε illuεtrated in Reaction Scheme XIII, Step 8, an acetaldehyde of Formula 308 iε oxidized to give the corresponding acid of Formula 309. An acetaldehyde of Formula 308 is reacted with 1 to 3 (preferably 1.5) molar equivalentε of a εuitable oxidizing agent (such as εilver oxide, Joneε reagent or preferably εodium chlorite) in the presence of an equimolar amount of a phenol (such as quinol or preferably reεorcinol) . The reaction is conducted in a mixture of water and a water-miscible organic εolvent (εuch aε tetrahydrofuran or preferably dioxane) at a pH of from 4 to 6 (preferably 5) at -10 to 25°C (preferably 0°C) for 10 minutes to 2 hourε (preferably 30 minuteε) to give the corresponding acid of Formula 309. Preparation of Formula IC As illuεtrated in Reaction Scheme XIII, Step 9, an acid of Formula 309 is deprotected to give the correεponding acid of Formula IC. An acid of Formula 309 where R* is a εulphonyloxy protecting group hydrolyzed under baεic conditionε, uεing from 1 to 5 (preferably 3) molar equivalentε of an alkali metal hydroxide (preferably lithium hydroxide) in a mixture of water and a water-miεcible organic εolvent (such as dioxane or preferably methanol) . The reaction takes place at 40 to 100°C (preferably 60°C) for 1 to 48 hourε (preferably 12 hourε) to afford the correεponding cyclopentene carboxylic acid of Formula IC. Alternatively, for other protecting groupε, the deprotection reaction takeε place as described above with reference to Reaction Scheme X, Step 1. Preparation of Compounds of Formula ID One method of preparing compoundε of Formula 1 where Z is a sidechain of Formula ZD, illustrated as compounds of Formula ID, iε εhown below in Reaction Scheme XIV. REACTION SCHEME XIV Formu la 401 Formu la 103d iky l Formu I a 104a Formu la 402 Formu la 402 Formu la 403 Formu la 403 For ula 1D Preparation of Formula 401 As illustrated in Reaction Scheme XIV, Step 1, an aldehyde of Formula 103 (where R a iε a silyl protecting group) iε converted to a carbinol by addition of an organometallic compound of Formula 103d (εuch aε a εubεtituted vinyl organolithium, or preferably a Grignard reagent where: M iε MgBr or Li; Z 2 iε hydrogen or lower alkyl; and TBS is a tert- butyldimethylεilyl protecting group) . The aldehyde of Formula 103 iε reacted with from 1.1 to 1.5 (preferably 1.25) molar equivalentε of an organometallic, preferably organolithium, derivative of a protected 2-halo (preferably 2-bromo) but-1- en-4-ol. The reaction is performed at from -100 to -40°C (preferably at -78°C) for from 30 minuteε to 6 hourε (preferably 1 hour) to afford the corresponding compound of Formula 401. Preparation of Formula 402 As illustrated in Reaction Scheme XIV, Step 2, an alkyl ester of Formula 402 iε formed by a Claisen ortho ester rearrangement reaction of a carbinol of Formula 401 and a trialkyl orthoacetate of Formula 104a. A carbinol of Formula 401 is heated at 50 to 120°C (preferably about 100°C) with about 10 molar equivalents of an orthoester of Formula 104a, in the presence of from 0.05 to 0.25 (preferably 0.10) molar equivalents of an organic acid catalyst (such as propionic, butyric, or preferably trimethylacetic acid) . The reaction takes place over a period of 1 to 48 hourε (preferably 8 hours) to give the corresponding alkyl ester of Formula.4.02. Preparation of Formula 403 Aε illuεtrated in Reaction Scheme XIV, Step 3, an alkyl eεter of Formula 402 iε reacted with a tetraalkylammonium fluoride and then halogenated to give a protected ester of Formula 403. A compound of Formula 402 is reacted with from 2 to 3 (preferably 2) molar equivalents of a tetraalkylammonium (preferably tetrabutylammonium) fluoride, in a solvent (such as dioxane or preferably methylene chloride) at from 0 to 25 β C (preferably 10°C) , for from 30 minutes to 4 hourε (preferably 1 hour) . The product so obtained iε reacted with from l.0 to 1.5 (preferably 1.25) molar equivalentε of a halogenating agent (preferably a brominating agent, such aε triphenylphoεphine/carbon tetrabromide or preferably triphenylphoεphine/N-bromoεuccinimide) in a εolvent εuch aε ether or preferably dichloromethane. The reaction takeε place at from -40 to 0°C (preferably -10°C) for from 1 to 6 hourε (preferably 4 hours) to give the corresponding halogenated eεter of Formula 403. Preparation of Formula ID Aε illustrated in Reaction Scheme XIV, Step 4, a halogenated ester of Formula 403 iε cyclized to give a cycloalkyl eεter of Formula IC. A compound of Formula 403 iε reacted with from 2.0 to 2.5 (preferably 2.25) molar equivalentε of a εtrong baεe (εuch aε lithium diiεopropylamide, εodium hydride or preferably εodium hexamethyldiεilazide) in an ethereal εolvent (εuch as ether, dioxane or preferably tetrahydrofuran) The reaction takeε place at from -100 to -60°C (preferably -78°C) for 1 to 12 hours (preferably 4 hours) to give the cycloalkyl ester of Formula ID, which may be hydrolyzed to the carboxylic acid of Formula ID aε described above with reference to Reaction Scheme X, Step 2. Preparation of Compounds of Formula IE Methods of preparing compounds of Formula 1 where Z is sidechain of Formula ZE, illuεtrated as compoundε of Formula IE, iε εhown below in Reaction Schemeε XV to XVII. REACTION SCHEME XV kyl kyl Formula 502 Formula 503 Formula 503 Formula 504 Formula 504 Formula 103 Formula 505 Formula 505 Formula 506 Preparation of Formula 502 As illustrated in Reaction Scheme XV, Step 1, the 2-methyl group of an alkyl 2-methylbenzoate of Formula 501 (where Z 6 and Z 7 are selected from hydrogen, lower alkyl, lower alkoxy, lower alkoxycarbonyl, halo and nitro) iε brominated to give the corresponding compound of Formula 502. An eεter of Formula 501 iε reacted with 1.0 to 1.2 (preferably 1.05) molar equivalentε of a brominating agent (such aε N-bromoacetamide or preferably N-bromoεuccinimide) , optionally in the presence of an initiator (such as visible light) or from 0.001 to 0.01 (preferably 0.005) molar equivalents of a chemical initiator (εuch aε azobiεisobutyronitrile or preferably benzoyl peroxide) in a εolvent (εuch aε ethyl formate or preferably carbon tetrachloride) . The reaction takeε place at 40 to 80°C (preferably 75°C) for 30 minuteε to to 6 hourε (preferably 2 hourε) to afford the correεponding alkyl 2-bromomethylbenzoate of Formula 502, which can be purified by conventional meanε or preferably uεed directly for the next εtep. Preparation of Formula 503 As illustrated in Reaction Scheme XV, Step 2, a 2-bromomethyl group of Formula 502 is converted to the corresponding phosphonium εalt of Formula 503. A 2-bromomethylbenzoate of Formula 502 iε reacted with 1.0 to 1.25 (preferably 1.05) molar equivalentε of a triaryl phoεphine (preferably triphenyl phoεphine) in a εolvent (εuch aε dimethylformamide or preferably acetonitrile) . The reaction takeε place at 25 to 90°C (preferably 50°C) for 1 to 24 hourε (preferably 2 hourε) to afford the corresponding phosphonium εalt of Formula 503. Preparation of Formula 504 Aε illuεtrated in Reaction Scheme XV, Step 3, a phoεphonium εalt of Formula 503 iε converted to the correεponding εubεtituted benzylidenetriphenylphoεphorane ylid of Formula 504. A phosphonium salt of Formula 503 iε diεεolved or εuspended in a solvent (such as dioxane, ether or preferably dimethylformamide) and reacted with 1.0 to 1.25 (preferably 1.05) molar equivalents of a baεe (such as sodium hydride, triethylamine or preferably 1,5- diazabicyclo[4.3.0]non-5-ene) . The reaction takeε place at 0 to 60°C (preferably 25°C) for 1 to 6 hours (preferably 2 hourε) to afford the correεponding ylid of Formula 504, which can be iεolated by conventional meanε or itε εolution can be used directly for the next step. Preparation of Formulae 505 and 506 As illuεtrated in Reaction Scheme XV, Step 4, an ylid of Formula 504 and a protected aldehyde of Formula 103 (prepared, for example, aε deεcribed in connection with Reaction Scheme ZA-A, Step 2) are employed in a Wittig reaction to give the correεponding protected εubεtituted benzoic acid alkyl eεter of Formula 505 aε a mixture of E and Z iεomerε, from which the deεired E iεomer of Formula 506 iε iεolated, aε illuεtrated in Reaction Scheme XV, Step 5. A solution of 0.8 to 1.0 (preferably 0.95) molar equivalents of a protected aldehyde of Formula 103 in a solvent (such aε ether, dioxane or preferably dimethylformamide) iε added to a εolution of an ylid of Formula 504 in the εame εolvent. The reaction takeε place at 0 to 50°C (preferably 25°C) for 1 to 24 hourε (preferably 12 hourε) to afford the correεponding protected εubεtituted benzoic acid alkyl ester of Formula 505 aε a mixture of E and Z iεomerε, from which the deεired E-iεomer of Formula 506 can be isolated by conventional means (εuch aε diεtillation, chromatography or preferably fractional cryεtallization) . REACTION SCHEME XVI Formula 507 Formula 508 Formula 509 Formula 510 Formula 510 Formula 511 Preparation of Formula 508 As illustrated in Reaction Scheme XVT, Step 1, the alpha carbon of an alkyl 2-alkylbenzoate of Formula 507 (where Z s is hydrogen or lower alkyl, and Z 6 and Z 7 are εelected from hydrogen, lower alkyl, lower alkoxy, lower alkoxycarbonyl, halo and nitro) iε brominated to give the correεponding compound of Formula 508. The reaction takeε place under the conditionε deεcribed with reference to Reaction Scheme XV, Step 1. Preparation of Formula 509 Aε illuεtrated in Reaction Scheme XVI, Step 2, an alkyl 2-bromo- alkylbenzoate of Formula 508 and a trialkyl phosphite are combined in an Arbuzov reaction to give the correεponding phoεphonate of Formula 509. A compound of Formula 508 iε reacted with from 5 to 20 (preferably 10) molar equivalents of a trialkyl phosphite (preferably triethyl phoεphite) . The reaction takeε place at 100 to 200°C (preferably 150°C) for 1 to 24 hourε (preferably 6 hours) to afford the corresponding phosphonate of Formula 509. Preparation of Formulae 510 and 511 . As illustrated in Reaction Scheme XVI, Step 3, a phoεphonate of Formula 509 and a protected aldehyde of Formula 103 (prepared, for example, aε deεcribed in connection with Reaction Scheme I, Step 2) are reacted to give the correεponding protected εubεtituted benzoic acid alkyl eεter of Formula 510 aε a mixture of E and Z isomers, from which the desired E iso er of Formula 511 iε iεolated, aε illuεtrated in Reaction Scheme XV, Step 4. A phoεphonate of Formula 509 is reacted with 1.0 to 1.5 (preferably 1.1) molar equivalentε of a baεe such (as εodium amide, potassium tert-butoxide or preferably sodium hydride) for from 1 to 4 hours (preferably 2 hourε) at 0 to 50°C (preferably 25°C) in a εolvent (εuch aε dioxane, dimethylformamide or preferably dimethoxyethane) , to give a εolution or εuεpenεion of the correεponding alkali metal εalt of Formula 509, which iε employed without iεolation or further purification. The alkali metal salt is reacted with from 0.9 to 1.1 (preferably 1.0) molar equivalents of a protected aldehyde of Formula 103, dissolved in the εame solvent. The reaction takeε place at 0 to 60°C (preferably 40°C) for 1 to 6 hourε (preferably 2 hourε) to afford the correεponding protected optionally εubεtituted benzoic acid alkyl eεter of Formula 510 aε a mixture of E and Z ■iεomers, from which the deεired E-iεomer of Formula 511 can be iεolated by conventional meanε (εuch aε diεtillation, chromatography or preferably fractional cryεtallization) . REACTION SCHEME XVII Formula 103 Br gCHSiCCH 3 3 3 Formula 513 Formula 512 Formu la 514 Formu I a 5 4 Formula 515 where R a is TBDMS where R B i s acy Formula 515 Formula 511 Formula 516 Preparation of Formula 513 As illustrated in Reaction Scheme XVII, Step 1, a protected aldehyde of Formula 103 iε converted to a trialkylεilylcarbinol of Formula 513 in a Grignard reaction. An aldehyde of Formula 103 iε reacted with from 1.0 to 1.25 (preferably 1.1) molar equivalents of a trialkylεilylalkyl-magneεium bromide (such as trimethylεilylpropylmagneεium bromide, or preferably trimethylsilylmethylmagneεium bromide) of Formula 512, in an ethereal solvent (εuch as ether, dimethoxyethane or preferably tetrahydrofuran) . The reaction takeε place at -40 to 40°C (preferably 0°C) for 30 minutes to 4 hours (preferably 1 hour) to give the corresponding trialkylsilylcarbinol of Formula 513. Preparation of Formula 514 As illustrated in Reaction Scheme XVII, Step 2, a protected trialkylεilylcarbinol of Formula 513 iε dehydrated to give the corresponding protected alkene as a mixture of E and Z isomers, from which the desired Z isomer of Formula 514 is isolated. A carbinol of Formula 513 iε reacted with from 1.0 to 1.5 (preferably 1.05) molar equivalentε of a εulphonyl chloride (εuch as p-toluenesulphonyl chloride or preferably methanesulphonyl chloride) in the presence of the same molar proportion of a tertiary organic baεe (εuch aε N-methyl- pyrrolidine or preferably triethylamine) . The reaction takeε place at 0 to 40°C (preferably 15°C) for 30 minuteε to 4 hourε (preferably 2 hourε) to afford the correεponding protected alkene of Formula 514 aε a mixture of E and Z iεomerε, from which the deεired Z-iscmer of Formula 514 can be isolated by conventional means (εuch as distillation, chromatography or prefers-bly fractional crystallization) . Preparation of Formula 515 As illustrated in Reaction Scheme XVII, Step 3, an alkene of Formula 514 where R m iε a εilyl protecting group iε converted to an alkene of Formula 515 where R" iε an acyl group. An alkene of Formula 514 iε heated at 50-130°C (preferably about 118°C) with a large exceεs of a mixture (preferably about equimolar) of a carboxylic acid of Formula R"OH and an anhydride of Formula (R") 2 0 (where R" is the desired acyl group) , preferably a mixture of acetic acid and acetic anhydride. The reaction takeε place over a period of 6 to 48 hourε (preferably 18 hourε) to give the correεponding alkene of Formula 515 where R" iε the acyl group. Preparation of Formula 511 Aε illuεtrated in Reaction Scheme XVTI, Step 4, a protected alkene of Formula 515 iε converted to a protected optionally εubstituted benzoic acid alkyl eεter of Formula 511 in a Heck reaction with an alkyl-2-halo-benzoate of Formula 515. An alkene of Formula 515 is reacted with 1.0 to 2.0 (preferably 1.25) molar equivalentε of an alkyl 2-halobenzoate (εuch as an alkyl 2-bromobenzoate or preferably 2-iodobenzoate) . The reaction is conducted in the presence of from 0.001 to 0.1 (preferably 0.05) molar equivalents of a palladium catalyst [such aε tetrakiε (tri-o-tolylphoεphine) palladium, or tetrakiε (triphenylphosphine)palladium or preferably palladium (II) acetate] optionally'in the presence of from 1.0 to 1.25 (preferably 1.05) molar equivalentε of a baεe (εuch εilver carbonate, sodium bicarbonate or preferably triethylamine) , in a εolvent (εuch aε acetonitrile or preferably dimethylformamide) . The reaction iε conducted at from 0 to 120°C (preferably 60°C) for 1 to 48 hourε (preferably 6 hourε) to yield the correεponding protected optionally εubstituted benzoic acid alkyl ester of Formula 511. Preparation of Formula IE The protected optionally subεtituted benzoic acid eεter of Formula 506 or Formula 511 are then deprotected to give the correεpbnding eεter of Formula IE. The deprotection reaction takeε place aε deεcribed above with reference to Reaction Scheme X, Step 1. The optionally εubεtituted benzoic acid eεter of Formula IE may then be hydrolyzed to give the correεponding acid of Formula IE aε described above with reference to Reaction Scheme X, Step 2. Preparation of Formula IE where Z* is Amino The compounds of Formula IE where Z 6 is nitro are employed aε precurεorε to the correεponding compoundε of Formula IE where Z 6 iε amino. The nitro compounds are also active aε IMPDH inhibitorε when teεted aε deεcribed below. A nitrobenzoic acid of Formula IE (where Z 6 iε nitro) iε reacted with 1.0 to 3.0 (preferably 2.0) molar proportions of a reducing agent (εuch as sodium hydrosulfite or preferably tin (II) chloride) in hydrochloric acid solution, optionally in the presence of a water-miscible co-solvent (such aε methanol or preferably acetic acid) . The reaction takeε place at 25 to 100°C (preferably 75°C) for 1 to 24 hourε (preferably 4 hours) to afford the corresponding amino-εubεtituted benzoic acid of Formula IE (where Z 6 iε amino) . REACTION SCHEME XVIII Formu la 509 . + Formula Formula Formula 520 Formu I a I-2E-D1 «- Formula I - ZE-D2 Step 5 Step 6 Preparation of Formula 517 As illuεtrated in Reaction Scheme XVIII, Step 1, a phoεphonate of Formula 509 undergoeε a baεe catalyzed condenεation (e.g., uεing 1 molar equivalent of εodium hydride) with tetrahydropyranyloxyacetaldehyde, in a solvent such as dimethylformamide. The reaction takeε place at 25°C over a period of 1 to 4 hourε, to give E/Z mixture from which the deεired product of Formula 517 can be iεolated by conventional meanε, εuch aε chromatography. Preparation of Formula 518 As illustrated in Reaction Scheme XVTII, Step 2, the tetrahydropyranyloxy group of a compoimd of Formula 517 iε hydrolyzed in the preεence of a catalytic amount of a dilute acid (e.g., HCl) in aqueouε tetrahydrofuran. The reaction takeε place at 25°C over a period of 1 to 4 hourε, to give the correεponding carbinol of Formula 518. Preparation of Formula 519 Aε illuεtrated in Reaction Scheme XVIII, Step 3, a carbinol of Formula 518 iε converted to the halo (e.g., chloro or bromo) derivative of Formula 519 uεing 1 molar equivalent of triphenylphoεphine and either carbon tetrachloride or carbon tetrabro ide, in dichloromethane. The reaction takeε place at 25°C over a period of 2 hourε. Preparation of Formula 520 Aε illuεtrated in Reaction Scheme XVTII, Step 4, a halo derivative of Formula 519 undergoeε a baεe-catalyzed ether formation with the indicated phenol, uεing 5 molar equivalentε of potaεsium carbonate, in dimethylformamide. The reaction takes place at 25°C over a period of 4 hours. Preparation of Formula IE As illuεtrated in Reaction Scheme XVTII, Step 5, an ether of Formula 520 iε rearranged to give the correεponding eεter of Formula IE by a thermal rearrangement catalyεed by floriεil. The rearrangement takeε place in toluene at 110°C over a period of one to four dayε. Aε illustrated in Reaction Scheme XVTII, Step 6, the ether εo- produced is hydrolyzed to the correεponding acid of Formula IE aε deεcribed with reference to Reaction Scheme X, Step 2. Preparation of Compounds of Formula IF One method of preparing compounds of Formula 1 where Z is a εidechain of Formula ZF, illuεtrated aε compoundε of Formula IF, iε εhown below in Reaction Scheme XIX. REACTION SCHEME XIX CH Formula 601 Formula 602 Formula 604 For u la 605 For u la 606 Preparation of Formula 602 Aε illuεtrated in Reaction Scheme XIX, Step 1, an aldehyde of Formula 601, prepared for example aε εhown in J. Orσ. Chem.. 1977, p3408, iε reduced to a carbinol of Formula 602. An aldehyde of Formula 601 iε reacted with a reducing agent capable of εelectively reducing an aldehyde in the presence of ester groupε, preferably from 1 to 2 (preferably 1.5) molar equivalentε of εodium borohydride in the presence of from 1 to 2 (preferably 1.5) molar equivalentε of cerium chloride trihydrate, in an alcoholic/ethereal εolvent mixture (preferably 4:1 tetrahydrofuran:methanol) . The reaction takes place at 0 to 40°C (preferably 25°C) for 10 minutes to 2 hours (preferably 30 minutes) to give the corresponding carbinol of Formula 602. Preparation of Formula 604 As illustrated in Reaction Scheme XIX, Step 2, a phenol of Formula 603 is alkylated with a carbinol of Formula 602 by meanε of the Mitεonobu reaction to give an ether of Formula 604. A carbinol of Formula 602 iε reacted with an equimolar amount of a phenol of Formula 603 in the presence of from 1 to 3 (preferably 2) molar equivalents of a triarylphosphine, preferably triphenylphosphine, plus from 1 to 3 (preferably 1.5) molar equivalentε of diethyl azodicarboxylate in an ethereal solvent (preferably tetrahydrofuran) . The reaction takeε place at 0 to 40 β C (preferably 25°C) for 1 to 10 hourε (preferably 3 hours) to give the correεponding ether of Formula 604. Preparation of Formula 605 Aε illuεtrated in Reaction Scheme XIX, Step 3, a phenol of Formula 604 iε thermally rearranged to give a dieεter of Formula 605. An ether of Formula 604 is heated in an inert solvent (preferably toluene) in the presence of about 10 parts by weight of an activated magnesium εilicate, preferably Floriεil ® . The reaction takeε place at reflux temperature for 1 to 10 days (preferably 4 days) to give the correεponding diester of Formula 605. Preparation of Formula 606 Aε illuεtrated in Reaction Scheme XIX, Step 4, a diester of Formula 605 iε hydrolyzed to give a dicarboxylic acid of Formula 606. A dieεter of Formula 605 is reacted with an excess of an inorganic baεe, preferably about 50 molar equivalentε of lithium hydroxide, in an aqueouε εolvent (preferably 5:1 methanol:water) . The reaction takeε place at 0 to 40°C (preferably 25°C) for 1 to 10 days (preferably 2 days) to give the corresponding dicarboxylic acid of Formula 606. Preparation of Formula IF Aε illuεtrated in Reaction Scheme XIX, Step 5, a dicarboxylic acid of Formula 606 iε decarboxylated to give a monocarboxylic acid of Formula IF. A dicarboxylic acid of Formula 606 iε heated (optionally in the presence of a high boiling inert εolvent, for example tetramethylbenzene, but preferably in the abεence of any εolvent) . The reaction takeε place at 160 to 240°C (preferably 195°C) for about 5 minuteε to give the correεponding monocarboxylic acid of Formula IF. Preparation of Compounds of Formula IG One method of preparing compounds of Formula 1 where Z is εidechain of Formula ZG, illustrated as compoundε of Formula IG, is shown below in Reaction Scheme XX. REACTION SCHEME XX For u la 701 Formu la 702 For u la 703 10 Formula 704 25 Formu I a 705 Formula 706 Formu la 707 45 Formu la 707 Formula 70B Formu la 70E Formu la 709 Formu la 709 Formu la 710 Formula 710 Formu la 711 Formu I a 7 1 For mu I a 1 G Preparation of Formula 703 As illustrated in Reaction Scheme XX, Step 1, the phenol of Formula 701 is alkylated with 3-hydroxycyclohexene to give the corresponding ether of Formula 703, by means of the Mitεonobu reaction. The Mitsonobu reaction takeε place aε deεcribed with reference to Reaction Scheme XIX, Step 2. Similarly, by εubstituting 3-cyclohexene with 3-cycloheptene, and carrying out the procedures of Reaction Scheme XX, the corresponding compoundε where Z iε a εide chain of Formula ZG where D 3 iε -CH--CH-- are obtained. Preparation of Formula 704 As illustrated in Reaction Scheme XX, Step 2, a Claisen rearrangement of the ether of Formula 703 gives the alkylated phenol of Formula 704. The reaction takes place, e.g., at 200°C for 12 to 16 hourε in the preεence of N,N-diethylaniline. Preparation of Formula 705 Aε illuεtrated in Reaction Scheme XX, Step 3, the alkylated phenol of Formula 704 iε protected to give a protected phenol of Formula 705 (where R* iε εilyl or toεyl) . An alkylated phenol of Formula 704 iε reacted with an equimolar amount of t-butyl dimethylsilyl chloride or p-tolueneεulfonyl chloride, in the preεence of an equimolar amount, reεpectively, of imidazole or 4- dimethyla inopyridine. The reaction takeε place in dichloromethane at a temperature of 25°C for 1 to 4 hourε to give the correεponding protected phenol of Formula 705. Preparation of Formula 706 Aε illustrated in Reaction Scheme XX, Step 4, a protected phenol of Formula 705 iε converted to the correεponding dialdehyde of Formula 706 by ozonolyεiε. The ozonolyεiε reaction takeε place aε deεcribed with reference to Reaction Scheme I, Step 2. Preparation of Formula 707 Aε illuεtrated in Reaction Scheme XX, Step 5, an intramolecular baεe- catalyzed aldol reaction with a dialdehyde of Formula 706 produceε the correεponding formyl cyclopentene of Formula 707. The reaction is conducted with 0.1 moles of dibenzylamine or n-methylaniline trifluoroacetate in benzene, taking place at 50°C for 30 minutes. Preparation of Formula 708 Aε illuεtrated in Reaction Scheme XX, Step 6, a formyl cyclopentene of Formula 707 iε reduced to the corresponding carbinol. The reaction employs sodium borohydride/cerium chloride, as described with reference to Reaction Scheme XIX, Step 1. Preparation of Formula 709 As illuεtrated in Reaction Scheme XX, Step 7, a carbinol of Formula 708 iε converted to the correεponding acetate of Formula 709. The reaction is conducted with equimolar amountε of acetyl chloride and triethylamine, taking place in methylene chloride at 0°C for 1 hour. Preparation of Formula 710 Aε illuεtrated in Reaction Scheme XX, Step 8, an acetate of Formula 709 iε converted to the corresponding diester of Formula 710. The reaction is conducted aε deεcribed in J. Am. Chem. Soc , 102:4730 (1980), with 4 moles of sodium dimethylmalonate, 0.5 moles triphenylphosphine and 0.25 moles of tetrakis triphenylphoεphine palladium at 50°C in tetrahydrof ran . Preparation of Formula 711 Aε illuεtrated in Reaction Scheme XX, Step 9, an dieεter of Formula 710 iε converted to the correεponding eεter of Formula 711, by reaction with ceεium acetate in hexamethylphoεphoric triamide at 120°C for l to 3 hourε. Preparation of Formula IG As illustrated in Reaction Scheme XX, Step 10, an eεter of Formula 711 iε hydrolyzed to give the correεponding compound of Formula IG. The reaction takeε place aε deεcribed with reference to Reaction Scheme X, Step 2. Preparation of Compounds of Formula IH One method of preparing compoundε of Formula 1 where Z iε εidechain of Formula ZH, illustrated as compoundε of Formula IH, iε εhown below in Reaction Scheme XXI. REACTION SCHEME XXI Formu la 103e Formu la 801 Formu la B01 Formu I a 802 Formu la 802 Formu l a B03 Formu la 803 Formu l a 804 Formu la 604 Formula 805 For mu I a 1 H Preparation of Formula 801 Aε illuεtrated in Reaction Scheme XXI, Step 1, an aldehyde of Formula 103 iε converted to a carbinol by addition of an organometallic compound of Formula 103e (such as a subεtituted vinyl organolithium, or preferably a Grignard reagent, where M is MgBr; TBS is a tert-butyldimethylsilyl protecting group; and n iε 3-5) . A halovinyl (preferably bromovinyl) compound of Formula 103e (where M is halo) iε reacted with magnesium metal in an ethereal solvent (εuch aε ether or preferably tetrahydrofuran) . The reaction takes place at 30 to 60°C (preferably 40°C) over a period of 1 to 6 hourε (preferably 2 hours) . One molar equivalent of the resultant organometallic reagent is added to a εolution of an aldehyde of Formula 103 (in the same solvent εyεtem uεed to make the organometallic reagent) . The reaction takeε place at -80 to 20°C (preferably 0°C) over a period of 5 to 60 minutes (preferably 10 minutes) to give the corresponding εilyl-protected carbinol of Formula 801. Preparation of Formula 802 As illustrated in Reaction Scheme XXI, Step 2, an alkyl ester of Formula 802 is formed by a Claisen ortho eεter rearrangement reaction of a carbinol of Formula 801 and an orthoeεter compound of Formula 104a (aε illuεtrated in Reaction Scheme I, where Z 3 and Z 4 are hydrogen) . A silyl-protected carbinol of Formula 801 iε heated at 50 to 120°C (preferably about 100°C) with about 10 molar equivalents of an orthoester of Formula 104a, in the presence of from 0.05 to 0.25 molar equivalents (preferably 0.10 molar equivalents) of an organic acid catalyεt (εuch aε propionic, butyric, or preferably trimethylacetic acid) . The reaction takeε place over a period of 1 to 48 hourε (preferably 8 hours) to give the correεponding alkyl eεter of Formula 802. Preparation of Formula 803 Aε illuεtrated in Reaction Scheme XXI, Step 3, the εilyl-protected carbinol of an alkyl eεter of Formula 802 iε deprotected. A compound of Formula 803 iε reacted with from 5 to 30 (preferably 20) molar equivalentε of hydrogen fluoride, in a mixture of water and a water-miεcible organic solvent (preferably acetonitrile) . The reaction takes place at -20 to 40°C (preferably 25°C) for 5 to 60 minutes (preferably 30 minuteε) to afford the corresponding unprotected carbinol/alkyl ester of Formula 803. Preparation of Formula 804 As illustrated in Reaction Scheme XXI, Step 4, a carbinol of Formula 803 is converted to a halide (preferably a bromide) of Formula 804, by means of a one-step or a two-step procedure. In the one-step procedure, a carbinol of Formula 803 iε reacted with from 1.0 to 1.3 (preferably 1.1) molar equivalentε of a triaryl (preferably triphenyl) phosphine, and from 1.0 to 1.3 (preferably 1.1) molar equivalents of a halogen εource (εuch aε N-bromoεuccinimide or preferably carbon tetrabromide) . The reaction iε conducted in an inert εolvent (εuch aε ether or preferably tetrahydrofuran) . The reaction takeε place at 0 to 50°C (preferably 25°C) for l to 12 hourε (preferably 3 hourε) to afford the correεponding halide of Formula 804. Alternatively, in the two-εtep procedure, which iε preferred, a carbinol of Formula 803 iε converted firεt into a sulphonate ester (such aε a p-tolueneεulphonate or preferably a methaneεulphonate) by reaction with from 1.0 to 1.5 (preferably 1.3) molar equivalentε a sulphonyl halide (preferably methanesulphonyl chloride) in the presence of an equimolar amount of a tertiary organic base (preferably diiεopropylethylamine) in a εolvent (εuch aε chloroform or preferably dichloromethane) . The reaction takeε place at -20 to 30°C (preferably 0°C) for 10 to 60 minuteε (preferably 30 minuteε) . The εo-obtained εulphonate ester is then reacted with from 5 to 20 (preferably 20) molar equivalentε of an alkali metal halide (preferably lithium bromide) in a εolvent' (εuch aε 2-butanone or preferably acetone) . The reaction takes place at 0 to 56°C (preferably at reflux) for 30 to 180 minutes (preferably 90 minutes) to afford the corresponding halide of Formula 804. Preparation of Formula 805 As illustrated in Reaction Scheme XXI, Step 5, a halogenated carbinol/alkyl ester of Formula 804 is deprotected at the phenolic group to give the corresponding halogenated carbinol/alkyl ester of Formula 805. The deprotection reaction takes place aε described above with reference to Reaction Scheme X, Step 1. Preparation of Formula IH Aε illuεtrated in Reaction Scheme XXI, Step 6, a halogenated carbinol/alkyl ester of Formula 805 is subjected to a base-induced cyclization reaction to afford the product of Formula IH. A compound of Formula 805 is reacted with from 2.0 to 2.5 (preferably 2.3) molar equivalentε of a εtrong baεe (such as lithium diiεopropylamide, sodium hydride or preferably εodium hexamethyldisilazide) in a solvent (εuch aε dioxane or preferably tetrahydrofuran) . The reaction takeε place at -20 to 30°C (preferably at 0°C) for 5 to 60 minuteε (preferably 15 minutes) to afford the corresponding cycloalkylester of Formula IH. The cycloalkyl ester of Formula I-ZH-Al may then be hydrolyzed to give the corresponding acid of Formula IH. The hydrolysiε takeε place aε described above with .reference to Reaction Scheme X, Step 2. Compounds of Formula 1 where Z is a εidechain of Formula ZH in which D" iε 0 or O-CH- are preferably prepared aε described below in Reaction Scheme XXII. REACTION SCHEME XXII F o r m u l a 806 F or mu l a 807 Formu l a 807 Formu l a B08 Formu l a 80B Fo mu l a B09 Formu l a 809 Formu l a 810 Formu l a B 10 For u la 1 H Preparation of Formula 807 Aε illuεtrated in Reaction Scheme XXII, Step 1, an aldehyde of Formula 302 (where Z 5 iε methyl) undergoeε an aldol reaction with the bromo-alkyl oxazolidinone of Formula 806 (where q iε 1 or 2) , which can be prepared by analogy with the reactionε deεcribed in J. Amer. Chem. Soc., 103, 2127, 1981, to give the acyloxazolidinone of Formula 807. An oxazolidinone of Formula 806 iε reacted with an equimolar amount of a baεe (εuch aε lithium diiεopropylamide or preferably di-n-butylboryl trifluoromethane εulphonate/triethylamine) , and then with an aldehyde of Formula 302. The reaction takeε place at -78°C to 0°C (preferably -40°C) for 1 to 12 hourε (preferably 3 hourε) to afford the correεponding acyloxazolidinone of Formula 807. Preparation of Formula 808 Aε illuεtrated in Reaction Scheme XXII, Step 2, an acyloxazolidinone of Formula 807 iε hydrolyzed to the carboxylic acid of Formula 808. An acyloxazolidinone of Formula 807 is reacted with 1-5 (preferably 3) molar equivalentε of lithium hydroxide in 3:1 tetrahydrofuran containing 5-20 (preferably 12) molar equivalents of hydrogen peroxide. The reaction takes place at -10 to 25 β C (preferably 0°) for 5 to 60 minuteε (preferably 30 minuteε) to give the correεponding carboxylic acid of Formula 808. Preparation of Formula 809 Aε illuεtrated in Reaction Scheme XXII, Step 3, a carboxylic acid of Formula 808 iε deprotected to give the correεponding phenol of Formula 809, uεing the method deεcribed with respect to Reaction Scheme X, Step 1. Preparation of Formula 810 A phenol of Formula 809 is esterified to give the corresponding ester of Formula 810. A phenol of Formula 809 is treated with methanol in the presence of 0.05 to 0.2 (preferably 0.1) molar equivalentε of an acid catalyεt (preferably p-tolueneεulphonic acid) . The reaction takeε place at 0 to 50°C (preferably 25°C) for 1 to 24 hours (preferably 12 hours) to give the corresponding methyl ester of Formula 810. Preparation of Formula IH A methyl ester of Formula 810 undergoes an intramolecular cyclization reaction to give the correεponding cyclized eεter of Formula IH. A methyl ester of Formula 810 is treated with 1.9 to 2.5 (preferably 2.0) molar equivalentε of a εtrong baεe (εuch aε lithium diiεopropylamide or preferably sodium hydride) in tetrahydrofuran (or preferably dimethylformamide) . The reaction takes place at -10 to 25°C (preferably 0°) for 1-12 hours (preferably 2 hourε) to give the correεponding cyclized ester of Formula IH, which may be hydrolyzed to give the corresponding acid of Formula IH, using the method deεcribed with reεpect to Reaction Scheme X, Step 2. Preparation of Esters of Formula 1 The esters of Formula 1 (compounds where G is not OH) can be prepared aε described in U.S. Patents Nos. 4,727,069 and 4,753,935, incorporated herein by reference, by deprotection of a precursor (e.g., as described with reference to Reaction Scheme X, Steps 1) or aε deεcribed below by attachment of a leaving group and itε replacement by the deεired eεter. Preparation of Intermediates of Formula A The preparation of an intermediate of Formula A iε εhown in Reaction Scheme XXIII telow. REACTI0N SCHEME XXIII Formu I a 1 Formula B where R iε a protecting group and Z* iε a sidechain of Formula Z as defined in the Summary of the Invention in which G is lower alkoxy. For ula B Formu I a C where Z b iε a εidechain of Formula Z aε defined in the Summary of the Invention in which G iε hydroxy. Formula C Formu I a D Formula E Formu I a F Formula A Formula A Preparation of Formula B As illustrated in Reaction Scheme XXIII, Step 1, a lower alkyl ester of Formula 1, prepared as deεcribed above, iε protected at the phenolic hydroxyl with an arylεulfonyl or alkylεulfonyl group. A compound of Formula 1 iε reacted with 1.0 to 1.1 (preferably 1.05) molar equivalentε of an arylεulfonyl or alkylsulfonyl halide (preferably p-toluenesulfonyl chloride) in pyridine. The reaction takes place at -10°C to 30°C (preferably room temperature) for 1 to 24 hours (preferably 12 hourε) . The protected correεponding compound of Formula B iε iεolated by conventional meanε (such as evaporation) . Preparation of Formula C As illustrated in Reaction Scheme XXIII, Step 2, a protected lower alkyl eεter of Formula B is demethylated in a cleavage reaction with 5 oleε of anhydrouε lithium iodide in a pyridine solvent (preferably collidine) . The reaction takes place at 50 to 75°C (preferably 60°C) for 10 hours to 8 days (preferably 4 days) . The corresponding protected 6- hydroxy acid of Formula C is iεolated by conventional meanε (such aε evaporation) . Preparation of Formula D Aε illustrated in Reaction Scheme XXIII, Step 3, a protected 6- hydroxy acid of Formula C iε esterified in an acid-catalyzed esterif cation. The reaction takeε place in a lower alkanol solvent (corresponding to the deεired lower alkyl ester, such aε methanol) with an acid (εuch aε p-tolueneεulfonic acid) at room temperature for 12 to 24 hourε (preferably 18 hourε) . The correεponding protected 6-hydroxy lower alkyl ester of Formula D iε isolated and purified by conventional means (such aε chromatography) . Preparation of Formula E As illuεtrated in Reaction Scheme XXIII, Step 4, a protected 6- hydroxy lower alkyl ester of Formula D is converted to the corresponding 6-triflate. The reaction takes place with the addition of 1.05 to 1.3 (preferably 1.2) molar equivalents of trifluoromethanesulfonic anhydride in a solvent (such as methylene chloride and/or pyridine) at -10°C to 10°C (preferably 0°C) for 15 minuteε to 10 hours (preferably 30 minuteε) . The correεponding protected 6-triflate of Formula E is isolated by conventional meanε (such aε evaporation) . Preparation of Trialkylstannanes of Formula 5a The trialkyl stannanes of Formula 5a are made by reaction of an organolithium or organomagnesium (Grignard) reagent with a trialkyl (preferably tributyl) tin chloride. The organolithium or organomagnesium reagents are either commercially available or are made conventionally, for example by halogen-metal exchange. Compounds in which R 7 contains a terminal triple bond can be reacted directly with butyllithiums to afford the organolithium compound. The butyl lithium reaction takeε place at -100°C to 0°C (preferably at -78°C) for 1 to 8 hourε (preferably 2 hours) to give the corresponding lithium derivative. The halide starting material iε reacted with magnesium metal in an ethereal solvent (preferably THF) under standard Grignard reaction conditions to give the magnesium halide derivative. The lithium or magnesium halide derivative iε reacted with a trialkylchloroεtannane (preferably tributylchlorostannane) in an ethereal εolvent (preferably THF) . The reaction takes place at -78°C to 0°C for 1 to 4 hourε (preferably 2 hourε) to give the correεponding trialkylεtannane of Formula 5a, which iε isolated and used in Reaction Scheme A, Step 5 without further purification. Tetramethyl, vinyltributyltin and phenyltributyl are all commercially available, e.g., from Aldrich. Preparation of Formula F Aε illuεtrated in Reaction Scheme XXIII, Step 5, a protected 6-triflate of Formula E is converted to the corresponding compound of Formula F where R 7 iε lower alkyl, cycloalkyl, vinyl, fluorovinyl, difluorovinyl, trifluorovinyl, alkenyl, -C≡C-R 11 , allenyl or CH 2 -0-(4- methoxybenzyl) by reaction with a trialkylεtannane of Formula 5a in the preεence of 6 moleε of lithium chloride and a palladium catalyεt [such aε triε (dibenzylidineacetone)dipalladium (O) chloroform adduct, or preferably tetrakiε- (triphenylphosphine)palladium] . The reaction takeε place in a polar aprotic solvent (preferably N-methylpyrrolidinone) at 50°C to 100°C (preferably 80°C) for 3 to 10 hourε (preferably 6 hours) . The 6-substituted protected lower alkyl eεter of Formula F is isolated and purified by conventional methods. The compoundε of Formula F where R 7 iε lower alkyl of two or more carbon atomε can be made by hydrogenation of the corresponding alkenyl compounds of Formula F, e.g., aε described below in Example 6. Preparation of Formula A As illustrated in Reaction Scheme XXIII, Step 6, a 6-εubstituted protected lower alkyl eεter of Formula F iε deprotected and converted to the corresponding acid by base hydrolysis. The compound of formula F iε reacted with 5 moles of a strong base (preferably lithium hydroxide) in an aqueous/lower alkanol solvent (such as methanol: ater) . The reaction takeε place at 50 to 70°C (preferably 60°C) for 10 to 24 hourε (preferably 16 hours) followed by acidification. The 6-substituted acid of Formula A where Z b is a sidechain of Formula Z aε defined in the Summary of the Invention in which G is hydroxy iε iε iεolated and purified by conventional meanε. Thiε 6-substituted acid can be converted to a compound of Formula A where Z" iε a εidechain of Formula Z aε defined in the Summary of the Invention in which G is lower alkoxy, by conventional means, for example aε shown in Step 3 above. Preparation of Formula A where R 7 is CH-OH and CHO The compounds of Formula A where R 7 is CI^OH and CHO (respectively designated Formulae A-2 and A-3) are prepared as deεcribed with reference to Reaction Scheme XXIV. REACTION SCHEME XXIV Formula A- 2 Formula A- 3 Preparation of Formula A-2 Aε illuεtrated in Reaction Scheme XXIV, Step 1, a 6- (4- methoxybenzyloxymethyl) εubεtituted compound of Formula A (εhown aε Formula A-l) iε debenzylated by reaction with 1 mole of a Lewiε acid (εuch aε boron tribromide or preferably boron trifluoride etherate) , or with 20 moleε of trifluoroacetic acid. The reaction takeε place in dichloromethane at -10°C to 5°C (preferably 0°C) for 30 minutes to 2 hours (preferably 1 hour) . Alternatively, when using trifluoroacetic acid, the reaction takes place at room temperature. The corresponding 6-hydroxymethyl compound of Formula A-2 iε iεolated and purified by conventional meanε. Preparation of Formula A-3 Aε illuεtrated in Reaction Scheme XXIV, Step 2, a 6-hydroxymethyl compound of Formula A-2 iε oxidized (uεing manganeεe dioxide or preferably one mole of pyridine chlorochromate) . The reaction takeε place in methylene chloride at -10°C to 5°C (preferably 0°C) for 8 to 24 hourε (preferably 12 hourε) . The correεponding 6-formyl compound of Formula A-3 iε isolated and purified by conventional means. Alternative Preparation of Formula A where R 7 is Lower Alkyl A compound of Formula A where R 7 is vinyl or alkenyl in converted to the correεponding lower alkyl compound by catalytic reduction in the preεence of 0.01 to 0.10 (preferably 0.02) moleε of triε(triphenylphoεphine)rhodium chloride. The reaction takeε place in an inert organic solvent (preferably 1:1 ethanol:benzene) at 20°C to 30°C (preferably 25°C) for 1 to 12 hours (preferably 2 hourε) . The correεponding compound of Formula A where R 7 iε lower alkyl (other than methyl) iε iεolated and purified by conventional meanε. Preparation of Intermediates of Formula 6 The p'reparation of a compound of Formula 6 is shown in Reaction Scheme XXV below. REACTION SCHEME XXV Formu la A Formu la 2 Formu l a 2 Formu la 3 For u la 4 Formula 4 For u la 5 For u l a 5 Formu la 6 Preparation of Compounds of Formula 2 Aε illustrated in Reaction Scheme XXV, Step 1, a phenol of Formula A is converted to the trifluoromethylsulfonyl compound of Formula 2. A compound of Formula A iε reacted in an inert organic εolvent, preferably dichloromethane, with about 1 to 3 molar equivalents, preferably about 2 molar equivalents, of a base, preferably pyridme, and with a slight excess, preferably about 1.1 molar equivalents, of a εulfonic anhydride, (εuch as a halo lower alkyl sulfonic anhydride, halomethyl εulfonic anhydride, and halosulfonic anhydride, or preferably trifluoromethanesulfonic anhydride or fluorosulfonic anhydride) or a sulfonyl halide, (such as trifluoromethylsulfonyl bromide, preferably trifluoromethylεulfonyl chloride) . The reaction iε carried out in the temperature range from about -20°C to 20°C, preferably at about 0°C, for about 15 to 45 minuteε, preferably about 30 minuteε. The trifluoromethylεulfonyl reaction product, a compound of Formula 2, iε iεolated and purified by conventional meanε. Preparation of Compounds of Formula 3 Aε illuεtrated in Reaction Scheme XXV, Step 2, a trifluoromethylεulfonyl derivative of Formula 2 iε converted to the cyano compound of Formula 3. A compound of Formula 2 iε reacted with about 1 to 3 molar equivalentε, preferably about 1.85 molar equivalents, of potassium cyanide with a catalytic amount of a triarylphoεphine palladium complex, preferably tetrakiε(triphenylphosphine) palladium, in an organic solvent, preferably 1,4-dioxane. The reaction iε carried out in the temperature range from about 70°C to 130°C, preferably at about the reflux temperature of 1,4-dioxane, for about 10 to 30 hours, preferably about 18 hours. The cyano reaction product, a compound of Formula 3, is isolated and purified by conventional meanε, preferably by extraction by an organic εolvent and column chromatography. Preparation of Compounds of Formula 4 Aε illuεtrated in Reaction Scheme XXV, Step 3, the cyano compound of Formula 3 iε hydrolyzed to the carboxy compound of Formula 4. A compound of Formula 3 iε hydrolyzed by reacting it with about 1 to 10 molar equivalentε, preferably about 4 molar equivalentε, of an inorganic baεe (e.g., εodium hydroxide, lithium hydroxide, or potaεsium hydroxide, preferably sodium hydroxide,) in a large excess of organic solvent, preferably in about 3:2 water:methanol solution. The reaction iε carried out in the temperature range from about 40°C to 130°C, preferably at about the reflux temperature of the 3:2 water/methanol εolvent, for about l to 3 hourε, preferably about 2 hourε. The reaction εolution iε diεtilled, and an additional of about 1 to 1.6 molar equivalentε, preferably about 1.3 molar equivalentε, of an inorganic baεe (e.g., εodium hydroxide, lithium hydroxide, or potaεεium hydroxide, preferably εodium hydroxide,) is added and the reaction iε continued in the temperature range from about 40°C to 130°C, preferably at about the reflux temperature of the remaining εolution, for about 1 to 3 dayε, preferably about 2 dayε. The reaction product, a compound of Formula 4, iε iεolated and purified by conventional meanε. Alternatively, the compound of Formula 4 may be prepared by reacting a correεponding compound of Formula 2 with a catalytic amount of 1,1' -biε (diphenylphoεphine)ferrocene palladium dichloride in a large exceεε of an alkanol (preferably methanol) in an organic εolvent (preferably trimethyl formamide) with a εlight exceεε, preferably 1.01 molar equivalents, of an organic base (preferably triethylamine) , under a carbon monoxide atmosphere of increased pressure of about 400-1000 PSI, preferably at about 600 PSI. The reaction product, which iε a dieεter of a compound of Formula 5, iε then hydrolyzed by reacting it with about 1 to 10 molar equivalentε, preferably about 4 molar equivalentε, of an inorganic baεe, preferably aqueouε lithium hydroxide, in a large exceεε of an organic εolvent, preferably 4:1 methanol/water εolution. The εolution is heated to a temperature range from about 30°C to 80°C, preferably from about 50°C to 60°C, for about 1 to 10 hours, preferably for about 2 to 6 hourε. The reaction product, a compound of Formula 4, iε iεolated and purified by conventional meanε. Preparation of Compounds of Formula 5 Aε illustrated in Reaction Scheme XXV, Step 4, a carboxy derivative of Formula 4 is converted to the ester of Formula 5. The compound of Formula 4 is reacted in a large exceεε of a compound of the formula GH, where G iε lower alkoxy, preferably methanol, with catalytic amountε of an acid catalyεt, preferably p-tolueneεulfonic acid. The reaction iε carried out in the temperature range from about 0°C to 40°C, preferably at about 20°C, for about 4 hourε to 3 dayε, preferably about 24 hourε. The reaction product, a 4-carboxy derivative of Formula 5, iε iεolated and purified by conventional meanε. Preparation of Compounds of Formula 6 Aε illuεtrated in Reaction Scheme XXV, Step 5, a 4-carboxy derivative of Formula 5 iε converted to the 4-iεocyanate derivative of Formula 6. A compound of Formula 5 is reacted with about 1 to 3 molar equivalentε, preferably about 2 molar equivalentε, of an organic baεe, preferably triethylamine, in a large excess of an organic solvent, preferably dimethylformamide, and about 1 to 2 molar equivalents, preferably about 1.3 molar equivalents, of an alkyl or phenyl haloformate or of a dialkyl or diphenyl halophosphate, preferably diphenyl chlorophosphate, in the temperature range from about -20°C to 20°C, preferably at about 0°C, allowing it to warm to the temperature range from about 0°C to 40°C, preferably at about 20°C, allowing the reaction to proceed for about 0.5 to 2 hours, preferably about 1 hour. The reaction mixture iε recooled to the temperature range from about -20°C to 20°C, preferably at about 0°C, and a large excess of sodium azide is added and the reaction proceeds for about 10 to 30 hourε, preferably about 18 hourε. The iεocyanato reaction product, a compound of Formula 6, iε iεolated and purified by conventional meanε. Alternatively, a compound of Formula 5 iε reacted with about 1 to 3 molar equivalentε, preferably about 2 molar equivalentε, of an organic base, preferably triethylamine, in a large excesε of an organic εolvent, preferably dimethylformamide, and with a slight exceεε, preferably 1.2 molar equivalentε, of a diphenyl or dialkyl phoεphoroazide, preferably diphenyl phoεphoroazide, in the temperature range from about 0°C to 40°C, preferably at about 20°C, for about 12 to 36 hourε, preferably for about 24 hourε. The iεocyanato reaction product, a compound of Formula 6, iε iεolated and purified by conventional meanε. PREPARATION OF COMPOUNDS OF FORMULA I In the following Reaction Schemeε, it εhould be noted that Z* repreεentε a εidechain of Formula Z aε defined in the Summary of the Invention in which G iε lower alkoxy, and Z b repreεentε a εidechain of Formula Z aε defined in the Summary of the Invention in which G iε hydroxy. 1. Preparation of Compounds of Formula I where R 1 and R 2 are both Hydrogen Compoundε of Formula I where R 1 and R 2 are both hydrogen are depicted aε Formula IA: Formula j _ The preparation of compoundε of Formula IA iε εhown in Reaction Scheme XXVI below. REACTION SCHEME XXVI Formu la 6 Formula u Formu la ^ Preparation of Formula IA where Z is Z b A compound of Formula 6 is hydrolyzed with about 1 to 20 molar equivalents, preferably 10 molar equivalents, of an inorganic base, preferably lithium hydroxide monohydrate, in an inert organic solvent, preferably 3:10 water:1,4-dioxane. The reaction is carried out in the temperature range from about 0°C to 40°C, preferably at about 20°C, for about 1 to 3 hourε, preferably about 2 hourε. The reaction product, a 4- amino compound of Formula IA where Z iε Z b , iε iεolated and purified by conventional meanε, preferably column chromatography. Preparation of Formula IA where Z is Z" A compound of Formula IA where Z iε Z iε eεterified with a lower alkanol of formula GH, where G iε lower alkoxy, aε described in the preparation of a compound of Formula D. Preparation of Compounds of Formula I where R 1 is Hydrogen and R 2 is -C(θ)NR"R 5 Compounds of Formula I where R 1 is hydrogen and R 2 iε -C(0)NR 4 R 5 are depicted aε Formula IB: Formula TR The preparation of compoundε of Formula IB is shown in Reaction Scheme XXVII below. REACTION SCHEME XXVII Formu la 6 Formula Ig Preparation of Formula IB where Z is Z* A compound of Formula 6 is reacted with a large excesε of an amine compound of the formula HNR*R 5 , where R 4 and R 5 are aε defined in the Summary of Invention, for example, methylamine, dimethylamine, methylphenylamine, ammonia, and the like, in an inert organic εolvent, preferably tetrahydrofuran. The reaction iε carried out in the temperature range from about 0°C to 40°C, preferably at about 20°C, for about 30 minuteε to 2 hourε, preferably about 1 hour. The reaction product, a 4- (optionally εubstituted ureido) ester of Formula IB where Z iε Z", iε iεolated and purified by conventional meanε. Preparation of Formula IB where Z is Z b An ester of Formula IB is hydrolyzed by reacting with about 1 to 10 molar equivalents, preferably about 4 molar equivalentε of an inorganic baεe, preferably aqueouε lithium hydroxide, in a large exceεε of an organic εolvent, preferably 4:1 methanol/water. The εolution iε heated to a temperature range from about 30°C to 80°C, preferably from about 50°C to 60°C, for about 1 to 10 hours, preferably for about 2 to 6 hours. The reaction product, a 4- (optionally subεtituted ureido) acid compound of Formula IB, is isolated and purified by conventional means. Preparation of Compounds of Formula I where R 1 is Hydrogen and R 2 is -C(θ)R 3 Compounds of Formula I where R 1 is hydrogen and R 2 is -C(0)R 3 are depicted as Formula IC: Formu la IC The preparation of compounds of Formula IC iε εhown in Reaction Scheme XXVTII below. REACTION SCHEME XXVTII ι3 Formula IA Formula IC Preparation of Compounds of Formula IC where Z is Z* A compound of Formula IA iε reacted in a large exceεε of an inert organic εolvent, preferably dichloromethane, with about 1 to 6 molar equivalentε, preferably about 2.5 molar equivalentε, of an anhydride compound of the formula (R 3 C(0)) 2 0 or of a acyl chloride of the formula R 3 C(0)C1, where R 3 iε aε defined in the Summary of the Invention. The reaction iε carried out in the temperature range from about 0°C to 40°C, preferably at about 20°C, for about 30 minuteε to 2 hourε, preferably about 1 hour. The reaction product, an amido ester of Formula IC, is isolated and purified by conventional meanε, preferably by recryεtallization. Preparation of Formula IC where Z is Z b A compound of Formula IC aε an eεter iε hydrolyzed aε deεcribed in the preparation of a compound of Formula IB to give a 4-amido compound of Formula IC aε a carboxylic acid. Preparation of Compounds of Formula I where R 1 is Lower Alkyl and R 2 is - C(0)R 5 Compoundε of Formula I where R l iε lower alkyl and R 2 iε -C(0)R 3 are depicted aε Formula ID: Formula ID The preparation of compounds of Formula ID is shown in Reaction Scheme XXIX below. REACTION SCHEME XXIX Formul a IC Preparation of Formula ID wherein R 1 is Lower Alkyl and Z is Z a A compound of Formula IC iε reacted with about 1 to 10 molar equivalentε, preferably about 4.5 molar equivalentε, of a weak baεe, preferably potaεsium carbonate, and with about 1 to 10 molar equivalents, preferably about 4 molar equivalents, of a lower alkyl bromide or iodide, preferably an iodide, in an inert organic εolvent, preferably dimethylformamide. The reaction iε carried out in the temperature range from about 0°C to 40°C, preferably at about 20°C, for about 12 to 48 hourε, preferably about 24 hourε. The organic layer is purified and then concentrated to an oil, to give an amide ester of Formula ID where R 1 is lower alkyl and G iε lower alkoxy. Preparation of Formula ID wherein R 1 is Lower Alkyl and Z is Z b An eεter of Formula ID where R 1 iε lower alkyl iε hydrolyzed as described in the preparation of a compound of Formula IB to give a carboxylic acid of Formula ID where R 1 iε lower alkyl. Preparation of Compounds of Formula I where R 1 is Lower Alkyl and R 2 is Hydrogen Compoundε of Formula I where R 1 is lower alkyl and R 2 is hydrogen are depicted as Formula IE: Formu la IE The preparation of compounds of Formula IE iε εhown in Reaction Scheme XXX below. REACTION SCHEME XXX Formu la D Formu la IE Preparation of Formula IE where R 1 is Lower Alkyl and Z is Z b An amido ester of Formula ID iε hydrolyzed by reacting with about 1 to 10 molar equivalentε, preferably about 4 molar equivalentε of an inorganic baεe (for example εodium hydroxide, preferably lithium hydroxide), in a large exceεε of an organic εolvent, preferably 4:1 methanol/water. The εolution is heated to a temperature range from about 50°C to 100°C, preferably from about 60°C to 80°C, for about 4 to 24 hours, preferably for about 12 hourε. The reaction product, a 4-alkylamino acid compound of Formula IE, iε iεolated and purified by conventional meanε. Preparation of Compounds of Formula I where G is Lower Alkoxy, Lower Thioalkoxy, or - (CHjJ-.-N-Y The compounds of Formula I where G is lower alkoxy, lower thioalkoxy, or -O- (CH 2 ) m -N=Y (i.e., the ester derivatives) may be prepared from the correεponding compoundε of Formula I where G iε hydroxy, including compoundε of Formulae IA, IB, IC, ID, and IE, by conventional meanε, for example as deεcribed in the preparation of a compound of Formula D. Preferred Preparation of Esters of Formula I where G is -0- (CH j ) m -N»y In a preferred procedure, a compound of Formula I where G is hydroxy iε esterified with an heterocyclic aminoalkyl alcohol of the formula GH, where G iε -O- (CH 2 ) πι -N=Y, in which m and Y are aε defined in the Summary of the Invention, by the direct esterification procedure described in the pending application entitled "Direct Esterification of Mycophenolic Acid", Serial No. 07/911635, filed July 10, 1992. In the direct esterification route, an acid compound of Formula I where G is hydroxy iε eεterified slowly in a refluxing inert organic solvent capable of azeotropic removal of water (such aε toluene, xylene, or a mixture thereof) using only a slight exceεε (between 1.01 to 1.20 molar equivalentε, and preferably, 1.05 to 1.06 molar equivalentε) of an heterocyclic aminoalkyl alcohol of the formula H0(CH 2 ) m -N=Y. Water generated by the reaction iε removed azeotropically. For example, with toluene aε the εolvent: 1) the reaction takeε place with (a) a reaction time of 20 to 120 hourε, preferably 50 to 100 hourε and moεt preferably 100 hourε and (b) an initial pot temperature range of 114 to 120°C increasing to a final pot temperature range of 118 to 130°C, preferably an initial pot temperature range of 115 to 118°C increasing to a final pot temperature range of 118 to 125°C, each depending on solute concentration and atmospheric preεεure, and moεt preferably an initial pot temperature of 116°C increaεing to a final pot temperature of 121°C with a ratio of the acid compound of Formula I (where G iε hydroxy) to toluene of lgm:2ml at one atmoεphere of pressure. The reaction product, a compound of Formula I where G is -O- (CH-) m -N=Y, iε iεolated and purified by conventional meanε. Salts of Compounds of Formula I Some of the compoundε of Formula I may be converted to corresponding baεe addition εaltε by virtue of the preεence of a carboxylic acid group. The conversion is accompliεhed by treatment with a εtoichiometric amount of an appropriate baεe, εuch aε potaεεium carbonate, sodium bicarbonate, ammonia, ethylenediamine, monoethanolamine, diethanolamine, triethanolamine and the like. Typically, the free acid is dissolved in a polar organic solvent εuch aε ethanol, methanol or ethyl acetate, and the baεe added in water, ethanol, methanol or iεopropanol. The temperature iε maintained at about 0°C to 50°C. The reεulting εalt precipitates εpontaneouεly or may be brought out of εolution with a leεε polar εolvent. The baεe addition εalts of the compounds of Formula I may be decomposed to the corresponding free acids by treating with at least a stoichiometric amount of a εuitable acid, such as hydrochloric acid or sulfuric acid, typically in the presence of aqueous solvent, and at a temperature of between about 0°C and 50°C. The free acid form iε iεolated by conventional meanε, εuch aε extraction with an organic εolvent. By virtue of the preεence of an amine group in the 4-poεition, some of the compounds of Formula I may be converted to the acid addition saltε by the εubεtitution of am organic or inorganic acid for the baεe in the above procedure. The acid εaltε can be decompoεed to the correεponding free bases by similar treatment with an appropriate base. Preferred Processes In summary, compounds of Formula I are prepared according to the following last steps: A process for preparing compounds of Formula I, wherein: R 1 iε hydrogen or lower alkyl; R 2 iε hydrogen, lower alkyl, -C(0)R 3 , -C(0)NR 4 R 5 , -C0 2 R 6 , or -S0 2 R 3 ; in which: R 3 iε hydrogen, lower alkyl, halo lower alkyl or optionally εubεtituted phenyl; R 4 iε hydrogen, lower alkyl or optionally εubεtituted phenyl; R 5 iε hydrogen, lower alkyl or optionally εubεtituted phenyl; R 6 iε lower alkyl or optionally εubεtituted phenyl; and R 7 iε lower alkyl, cycloalkyl, fluorovinyl, difluorovinyl, trifluorovinyl, lower alkenyl, -C≡C-R 8 , allyl, CHO, or CH j OR 9 ; in which: R 8 is hydrogen or lower alkyl, and R 9 iε hydrogen or 4-methoxybenzyl; and Z iε a εide chain εelected from Formulae ZA, ZB, ZC, ZD, ZE, ZF, ZG, and ZH: Formula ZA wherein: Z 1 iε hydrogen, lower alkyl, halo or CF 3 ; Z 2 iε hydrogen, lower alkyl, lower alkoxy, aryl, or -CTH j Z 13 , where Z 13 iε aryl or heteroaryl; Z 3 iε hydrogen, lower alkyl, lower alkenyl, lower alkoxy, phenyl, or -S(0) m Z 12 , where Z 12 iε lower alkyl, and m iε 0, 1 or 2; Z 4 is hydrogen, lower alkyl, or phenyl, or Z 3 and Z 4 taken together with the carbon to which they are attached form cycloalkyl of three to five carbon atoms; and G is OH, lower alkoxy, lower thioalkyl, -NG'G 2 , -0(CH 2 ).NG 1 G 2 , or - 0(CH 2 ) n N=G 3 , where n is an integer from 1 to 6, G 1 iε hydrogen or lower alkyl, G 2 iε hydrogen or lower alkyl, and =G 3 iε lower alkylene of four to εix carbon atomε, or lower alkylene of three to five carbon atomε pluε one member that iε -O-, -S-, or -N(G 4 ) - where G 4 iε hydrogen or lower alkyl; Formula ZB wherein: Z 5 is hydrogen or lower alkyl; Z 8 is hydrogen or lower alkyl; D 1 and D 2 together with their adjacent carbon atoms form an optionally substituted, saturated or unεaturated carbocyclic or heterocyclic ring of 3 to 7 atomε; and G iε aε defined above; or Formula ZC wherein: Z 5 , Z 8 , and G are aε defined above; or Formula ZD wherein: D 3 iε -CH 2 - or - Α_CH 2 - . a* 1 ' G iε aε defined above; or Formula ZE wherein: Z 6 iε hydrogen, lower alkyl, lower alkoxy, -COOH, -NH- or halo; Z 7 iε hydrogen, lower alkyl, lower alkoxy or halo; and Z 5 and G are aε defined above; or Formula ZF wherein: Z 1 and G are as defined above; or Formula ZG wherein: D 3 , Z 2 , Z 3 , Z 4 and G are as defined above; or Formula ZH wherein: D 4 is -CH--, -CH j CH j -, -CHjCHjCHj-, -0-, or -OCΑ_- ; and Z 1 and G axe as defined above; and the pharmaceutically acceptable salts thereof; which comprises a) reacting a compound of Formula I wherein G is lower alkoxy, lower thioalkyl, NG'G 2 , 0- (CH 2 ) B -NG 1 G 2 , or -O- (CH 2 ) B -N=G 3 , in which n, G 1 , G 2 , and G 3 are aε defined above, with an inorganic base to form a compound of Formula I wherein G is hydroxy; or b) reacting a compound of Formula I wherein G is hydroxy, with a compound of the formula GH, wherein G is lower alkoxy, lower thioalkyl, NG'G 2 , 0-(CH 2 ) n -NG'G 2 , or O- (CH 2 ) B -N=G 3 , in which n, G 1 , G 2 , and G 3 are as defined above, to form a compound of Formula I wherein G is lower alkoxy, lower thioalkyl, NG'G 2 , 0- (CH 2 ) a -NG'G 2 , or 0- (__H 2 ) B -N-_G 3 , in which n, G 1 , G 2 , and G 3 are as defined above; or c) reacting a compound of Formula I R 1 iε hydrogen and R 2 is-C(0)R 3 wherein R 3 is hydrogen, and G is lower alkoxy, with a compound of the formula HN ^, where R 4 and R s are independently hydrogen, lower alkyl or optionally εubstituted phenyl, to form a compound of Formula I wherein R 1 iε hydrogen and R 2 is-C(0)NE*R 5 wherein R 4 and R 5 axe independently hydrogen, lower alkyl or optionally substituted phenyl; or d) reacting a compound of Formula I wherein R l and R 2 are both hydrogen, and G is lower alkyl, optionally substituted phenyl, or - (CH 2 ) β - =Y, with a compound of the formula (R 3 C(0)) 2 θ or R 3 C(0)C1 wherein R 3 is as defined above, to form a compound of Formula I wherein R 2 is -C(0)R 3 , where R 3 is lower alkyl, halo lower alkyl or optionally substituted phenyl; or e) reacting a compound of Formula I wherein R 1 is hydrogen, R 2 is - C(0)R 3 wherein R 3 is as defined above and G is lower alkoxy, with a compound of the formula R'X, where R l is lower alkyl and X is iodine or bromine, to form a compound of Formula I wherein R 1 is lower alkyl; or f) converting a free compound of Formula I to a pharmaceutically acceptable salt of a compound of Formula I; or g) converting a pharmaceutically acceptable salt of a compound of Formula I to the free compound of Formula I; or h) converting a pharmaceutically acceptable salt of a compound of Formula I to another pharmaceutically acceptable salt of a compound of Formula I. Preferred Compounds Among the family of compounds of the present invention, one preferred category includes the compoundε where Z iε a εidechain of Formula ZA, ZB, ZE, and ZH, eεpecially where R 7 iε methyl, ethyl, vinyl, or cyclopropyl. Within thiε category a preferred group includeε the compounds where R 1 iε hydrogen, and R 2 iε hydrogen or trifluoroacetyl, eεpecially where G iε hydroxy or orpholinoethoxy. Within thiε group one preferred εubgroup includeε the compoundε where Z iε ZA and R 7 iε ethyl, eεpecially where Z 1 iε methyl, Z 2 iε hydrogen or methyl, and Z 3 and Z 4 are hydrogen. Another preferred εubgroup includeε the compounds where Z is ZB, and R 7 iε ethyl, eεpecially where D'-D 2 iε -(CH^- and Z 5 and Z 8 are hydrogen, more especially where R 2 is hydrogen. A third preferred subgroup includes the compounds where Z is ZE and R 7 is ethyl, especially where Z 5 and Z 7 are hydrogen and Z 6 is hydrogen or lower alkyl. A fourth preferred εubgroup includeε the compoundε where Z iε ZH and R 7 is ethyl, especially where Z 1 iε lower alkyl and D 4 is -CH 2 -, -CH,CH 2 -, or -0-CH 2 -. At present, the moεt preferred compoundε are: ( E ) -6- (4-amino-l,3-dihydro-6-ethyl-7-methyl-3-oxoisobenzofuran-5-yl) - 4-methyl-4-hexenoic acid; (E) -6- (4-amino-l,3-dihydro-6-ethyl-7-methyl-3-oxoisobenzofuran-5-yl) - 3,4-dimethyl- -hexenoic acid; and (E) -2-{2- [2- (4-amino-l,3-dihydro-6-ethyl-7-methyl-3-oxoiεobenzofuran- 5-yl) -ethylidene] -cyclopent-1-yl}acetic acid, utility, Testing and Administration General Utility The compounds of the present invention, the pharmaceutically acceptable salts thereof and pharmaceutical compoεitionε therewith (collectively the "compounds" for purposeε of the following deεcription) are uεeful aε im unosuppreεεive agentε, anti-inflammatory agentε, anti- tumor agentε, anti-proliferative agentε, anti-viral agentε and anti- pεoriatic agentε in mammals, whether domestic (cattle, pigs, sheep, goatε, horεeε) , petε (catε, dogε) , or preferably humanε. The compoundε are inhibitorε of inoεine monophoεphate dehydrogenaεe (IMPDH) and thus inhibit de novo purine synthesis; they have anti-proliferative effects (e.g., against smooth muscle cells and both B and T lymphocytes) and inhibit antibody formation and the glycosylation of cell adhesion molecules in lymphocytes and endothelial cell . Aε immunoεuppresεive agentε, the compoundε are useful in treating auto-immune related disorders, for example: Type I Diabeteε Mellituε; Inflammatory Bowel Diseaεe (e.g., Crohn'ε Diεease and Ulcerative Colitis); Syεtemic Lupuε Erythematoεuε; Chronic Active Hepatitis; Multiple Sclerosis; Grave's Disease; Hashimoto'ε Thyroiditiε; Behcet'ε Syndrome; Myaεthenia Graviε; Sjogren'ε Syndrome; Perniciouε Anemia; Idiopathic Adrenal Insufficiency; and Polyglandular Autoimmune Syndromes Type I and II. ■ The compoundε are alεo uεeful aε therapeutic immunosuppresεive agentε in the treatment of Aεthma, Immunohemolytic Anemia, Glomerulonephritiε, and Hepatitiε. Preventative uses bf the compounds as immunosuppresεive agentε include the treatment of allograft rejection, for example, in cardiac, lung, pancreatic, renal, liver, εkin and corneal allograftε, and prevention of Graft vε. Host Diseaεe. The compoundε are uεeful for inhibiting proliferative responseε to vascular injury, for example, stenosis following an insult to a blood vessel wall in post-angioplaεty reεtenoεiε, and post-cardiac by-pass surgery restenosis. The compounds are useful as anti-inflammatory agents, for example, in treating Rheumatoid Arthritiε, Juvenile Rheumatoid Arthritiε and ϋveitiε. Aε anti-tumor agents, the compounds are useful in treating solid tumors and malignancieε of lymphoreticular origin. For example, the compounds' utility for treatment of solid tumors includeε: cancerε of the head and neck, including εqua ouε cell carcinoma,- lung cancer, including email cell and non-small cell lung carcinoma,- mediastinal tumorε; eεophageal cancer, including εquamous cell carcinoma and adenocarcinoma; pancreatic cancer; cancer of the hepatobiliary syεtem, including hepatocellular carcinoma, cholangiocarcinoma, gall bladder carcinoma and biliary tract carcinoma; εmall inteεtinal carcinoma, including adenocarcinoma, εarco a, lymphoma auid carcinoidε; colorectal cancer, including colon carcinoma and rectal carcinoma; metaεtatic carcinoma; cancerε of the genitourinary εyεtem, including ovarian cancer, uterine εarcoma, and renal cell, ureteral, bladder, proεtate, urethral, penile, testicular, vulvar, vaginal, cervical, endometrial, and fallopian tube carcinoma; breast cancer; endocrine εystem cancer; soft tissue sarcomas; malignant mesotheliomaε; skin cancer, including εquamouε cell carcinoma, basal cell carcinoma and melanoma; cancer of the central nervous system; malignant bone tumors; and plasma cell neoplasmε. Aε anti-tumor agentε for the treatment of malignancieε of lymphoreticular origin, the compoundε are uεeful in treating, for example: Lymphomaε and Leukemiaε, including B, T and promonocyte cell line malignancies, Mycoseε Fungoideε, Non-Hodgkinε Lymphoma, Malignancies of Burkitt Lymphoma Cells and other EBV-transformed B-lymphocytes, Lymphomaε reεulting from Epεtein-Barr viral infections in allograft recipients, Chronic Lymphocytic Leukemia, Acute Lymphocytic Leukemia and Hairy Cell Leukemia. As anti-viral agents, the compounds are useful in treating, for example: retroviruses, including Human T-leukemia Viruεeε, Typeε I and II (HTLV-1 and HTLV-2) , Human Immuno Deficiency Viruεeε, Typeε I and II (HIV-1, HIV-2) and, Human Nasopharyngeal Carcinoma Virus (NPCV) and in treating Herpes Viruseε, including EBV infected B-lymphocyteε, CMV infection, Herpeε Viruε Type 6, Herpeε Simplex, Typeε 1 and 2, (HSV-1, HSV-2) and Herpeε Zoster. As anti-pεoriatic agentε, the compoundε are uεeful in treating, for example, pεoriaεiε and pεoriatic arthritiε. Testing Activity teεting iε conducted aε deεcribed in the following referenceε, and by modifications thereof. General anti-inflammatory, anti-viral, anti-tumor, anti-pεoriatic and/or immunoεuppreεεive activity iε aεεociated with the inhibition of Inoεine 5' -Monophoεphate Dehydrogenaεe ("IMPDH") . In vitro aεsays meaεuring the inhibition of IMPDH, for example, by determining the level of NADH formation according to the method of Anderεon, J.H. and Sartorelli, A.C., J. Biol . Chem. , 243:4762-4768 (1968) are predictive of εuch activity. Initial animal εcreening tests to determine anti-inflammatory activity potential include the adjuvant arthritis asεay, e.g., according to the method of Pearεon, Proc. Soc. Exp. Biol . Med. , 91:95-101 (1956) . Also, in vi tro testε, for example those using synovial explantε from patientε with rheumatoid arthritiε, ayer, et al., J. Exp. Med. , 145:1399-1404 (1977) , are uεeful in determining whether compoundε exhibit anti- inflammatory activity. Autoimmune activity is determined, for example, utilizing experimental allergic encephalomyelitis, by a modification of a procedure initially described by Grieg, et. al., J. Pharmacol . Exp. Ther. , 173:85 (1970) . Human clinical trials for efficacy in the treatment of asthma are conducted, e.g., as deεcribed by Erzurum, Leff, Cochran, et al. "Lack of benefit of methotrexate in severe, steroid-dependent asthma. A double- blind, placebo controlled study." Ann. Int . Med. , 114:353-360 (1991) . Activity to prevent the rejection of organ or tissue allografts in experimental animalε iε determined, for example, aε deεcribed by Hao, et al., J. Immunol . , 139:4022-4026 (1987) . In addition, U.S. Patent No. 4,707,443 and EP 226062, incorporated herein by reference, alεo deεcribe assays for activity in prevention of allograft rejection by detection of IL-2R levels. Human clinical trials to eεtabliεh efficacy in preventing rejection of solid organ transplantε (εuch aε renal) are conducted, e.g., as described by Lindholm, Albrechtsen, Tufveεon, et al., "A randomized trial of cycloεporin and predniεolone verεuε cyclosporin, azathioprine and prednisolone in primary cadaveric renal tranεplantation, " Transplantation, 54:624-631 (1992) . Human clinical trialε for graft vε. hoεt diεease are conducted, e.g., as described by Storb, Deeg, Whitehead, et al. , "Methotrexate and cyclosporin compared with cyclosporin alone for prophylaxis of acute graft versuε hoεt disease after marrow transplantation for leukemia." New England J. Med. , 314:729-735 (1986) . Immunoεuppreεεive activity iε determined by both in vivo and in vitro procedureε. In vivo activity iε determined, e.g., utilizing a modification of the Jerne hemolytic plaque assay, [Jerne, et al., "The agar plaque technique for recognizing antibody producing cells," Cell-bound Antibodies, Amos, B. and Kaprowski, H. editors (Wistar Institute Presε, Philadelphia) 1963, p. 109] . In vitro activity iε determined, e.g., by an adaptation of the procedure deεcribed by Greaveε, et al., "Activation of human T and B lymphocytes by polyclonal mitogenε," Nature, 248:698-701 (1974). Anti-viral activity iε determined, for example, by the procedure described by Smee, et al. ["Anti-Herpesviruε Activity of the Acyclic Nucleoεide 9- (l,3-Dihydroxy-2-Propoxymethyl)Guanine, " Antimicrobial Agents and Chemotherapy, 23 (5) :676-682 (1983)], or as described by Planteroεe ["Antiviral and cytotoxic effects of mycophenolic acid," Journal of General Virology, 4:629 (1969)] . Anti-viral activity can likewiεe be determined by measurement of reverse transcriptaεe activity, for example, according to the method deεcribed by Chen et al., Biochem. Pharm. , 36:4361 (1987) . Human clinical trialε for anti-HIV efficacy (together with clinical treatment scenarios) are deεcribed and cited, for example, by Sande, et al., "Antiretroviral Therapy for Adult HIV-Infected Patientε," JAMA, 270(21) :2583-2589 (1993). A large scale clinical trial can be conducted, e.g., as described by Volberding, P.A., et al. "Zidovudine in asymptomatic human immunodeficiency viruε infection: a controlled trial in persons with fewer than '500 CD4 positive cells per cubic millimeter, " New England J. Med. , 322(14) :941-949 (1990). A smaller scale (Phase I) clinical trial can be conducted, e.g., as described by Browne, et al., "2' ,3' -Didehydro-3' - deoxythymidine (d4T) in Patients with AIDS or AIDS-Related Complex: A Phase I Trial," J. Infectious Diseases, 167:21-29 (1993). Tests for systemic activity in psoriasis can be carried out, for example, aε deεcribed by Spatz, et al., "Mycophenolic acid in psoriaεis, " British Journal of Dermatology, 98:429 (1978) . Tests for anti-tumor activity can be performed, for example, as described by Carter, et al. ["Mycophenolic acid: an anticancer compound with unuεual propertieε," .Nature, 223:848 (1969)]. In vitro activity for treating εtenosiε iε demonεtrated, for example, by inhibiting the proliferation of εmooth muεcle cellε, as eεtabliεhed by the following human arterial εmooth muεcle cell proliferation assay. Human εmooth muεcle cells are grown in culture. A test group iε treated with the teεt compound added at εelected concentrationε in fresh media. Both groupε receive 2/_Ci tritiated thymidine ( 3 HTdR) , a radioiεotope label. After 24 hours, the cells are harvested and the amount of label incorporated into DNA iε counted by εcintillation; thiε iε compared for the test and control groupε, the amount being proportional to cell proliferation. Inhibition of εmooth muεcle proliferation iε eεtabliεhed when the teεt group haε a lower radioiεotope count than the control group. The concentrationε of teεt compound required to inhibit proliferation by 50% (the ICjo) and to inhibit proliferation by more than 95% are determined. In vivo activity for treating stenosis is demonstrated, for example, in rat and pig models for arterial stenosis. In the rat model, a test group is treated with the test compound, starting 6 days before and continuing for 14 days after injury to the left carotid artery; the test group is compared to a control group receiving vehicle without the test compound. Injury iε achieved by a gentle perfuεion of air through a 10 mm long εection of the left artery. The right artery iε left intact. Arterial croεε-εec . tionε (10 μm) are taken from both the left and right arterieε of each εubject, and the area of the veεsel wall (endothelium, intima, media) is meaεured, The amount of vaεcular proliferation iε calculated by εubtracting the mean area of the intact, right carotid artery from the mean area of the injured, left carotid artery. Reduction in vascular proliferation iε eεtabliεhed when the teεt group εhowε less proliferation than the control group. Human clinical trials for restenoεiε after coronary angioplasty are conducted, e.g., aε deεcribed by Serruys, Rutsch, Heyndrickx, et al., "prevention of restenoεiε after percutaneouε tranεluminal coronary antioplasty with thromboxane Aj-receptor blockade: a randomozed, double- blind, placebo-controlled trial." Circulation, 84:1568-80 (1991) . Administration The compounds of Formula I are administered at a therapeutically effective dosage, e.g., a dosage sufficient to provide treatment for the diseaεe εtateε previouεly deεcribed. Adminiεtration of the compounds of the invention or the pharmaceutically acceptable saltε thereof can be via any of the accepted modeε of adminiεtration for agentε that serve εimilar utilities. The compoundε can be uεed both prophylactically (e.g., to prevent allograft rejection) and therapeutically. While human doaage levelε have yet to be optimized for the compoundε of the invention, generally, a daily dose is from about 0.01 to 100.0 mg/kg of body weight, preferably about 0.1 to 64.3 mg/kg of body weight, and most preferably about 0.3 to 43.0 mg/kg of body weight. Thuε, for adminiεtration to a 70 kg person, the dosage range would be about 0.7 mg to 7 g per day, preferably about 7.0 mg to 4.5 g per day, and most preferably about 21 mg to 3.0 g per day. The amount of active compound administered will, of courεe, be dependent on the εubject and diεeaεe εtate being treated, the εeverity of the affliction, the manner and εchedule of adminiεtration (e.g., oral adminiεtration one day prior to cancer chemotherapy and intravenouε adminiεtration during cancer chemotherapy) and the judgment of the preεcribing phyεician. In employing the compounds of this invention for treatment of the above conditions, any pharmaceutically acceptable mode of administration can be used. The compounds of Formula I can be administered either alone or in combination with other pharmaceutically acceptable excipients, including solid, semi-solid, liquid or aerosol dosage forms, εuch as, for example, tablets, capεules, powders, liquids, injectableε, εuεpenεionε, suppositories, aerosols or the like. The compoundε of Formula I can alεo be administered in sustained or controlled release dosage forms, including depot injections, osmotic pumps, pills, transdermal (including electrotransport) patches, and the like, for the prolonged administration of the compound at a predetermined rate, preferably in unit dosage for ε suitable for single administration of precise dosageε. The compositions will typically include a conventional pharmaceutical carrier or excipient and a compound of Formula I or a pharmaceutically acceptable salt thereof. In addition, these compoεitionε may include other medicinal agents, pharmaceutical agents, carriers, adjuvants, etc., such as multidrug resistance modifying agents, steroids, immunoεuppreεεantε such as cyclosporine A, azathioprene, rapamycin, FK-506, brequinar, leflunomide and vincryεtine. Generally, depending on the intended mode of adminiεtration, the pharmaceutically acceptable compoεition will contain about 0.1% to 90%, preferably about 0.5% to 50%, by weight of a compound or εalt of Formula I, the remainder being εuitable pharmaceutical excipients, carriers, etc. One preferred manner of administration for the conditions detailed above is oral, using a convenient daily doεage regimen which can be adjusted according to the degree of affliction. For εuch oral administration, a pharmaceutically acceptable compoεition iε formed by the incorporation of any of the normally employed excipientε, εuch as, for example, mannitol, lactose, starch, povidone, magnesium stearate, sodium saccharine, talcum, cellulose, croεcarmelloεe sodium, glucose, gelatin, sucrose, magnesium carbonate, and the like. Such compositionε take the form of εolutionε, εuεpenεionε, tabletε, diεperεible tabletε, pillε, capεuleε, powderε, sustained releaεe formulationε and the like. Preferably the compoεitionε will take the form of a pill or tablet and thuε the compoεition will contain, along with the active ingredient, a diluent εuch aε lactoεe, εucrose, dicalcium phosphate, or the like; a lubricant εuch aε magneεium εtearate or the like; a diεintegrant such aε croεcarmellose εodium or the like; and a binder such as εtarch, gum acacia, polyvinylpyrrolidine, gelatin, cellulose and derivatives thereof, and the like. Liquid pharmaceutically administrable compoεitionε can, for example, be prepared by diεεolving, diεpersing, etc. an active compound aε defined above and optional pharmaceutical adjuvantε in a carrier, such as, for example, water, saline, aqueouε dextroεe, glycerol, glycolε, ethanol, and the like, to thereby form a εolution or εuεpenεion. If desired, the pharmaceutical composition to be administered may alεo contain minor amounts of nontoxic auxiliary subεtanceε εuch as wetting agentε, εuspending agents, emulεifying agentε, or εolubilizing agentε, pH buffering agentε and the like, for example, εodium acetate, sodium citrate, cyclodextrine derivativeε, polyoxyethylene, sorbitan monolaurate or stearate, etc. Actual methods of preparing such dosage forms are known, or will be apparent, to those skilled in this art; for example, see Remington 's Pharmaceutical Sciences, Mack Publishing Company, Easton, Pennsylvania, 15th Edition, 1975. The composition or formulation to be administered will, in any event, contain a quantity of the active compound in an amount effective to alleviate the symptomε of the εubject being treated. Doεage forms or compositionε containing active ingredient in the range of 0.005% to 95% with the balance made up from pharmaceutically acceptable carrier may be prepared. For oral administration, a pharmaceutically acceptable composition is formed by the incorporation of any of the normally employed excipients, such aε, for example pharmaceutical gradeε of mannitol, lactoεe, εtarch, magneεium εtearate, talcum, povidone, celluloεe derivativeε, croscarmellose εodium, glucoεe, εucrose, magnesium carbonate, sodium saccharin, talcum and the like. Such compositionε take the form of solutions, εuεpenεionε, tabletε, capεules, powders, sustained release formulations and the like. Such compositionε may contain 0.01%-95% active ingredient, preferably 0.1-50%. For a εolid doεage form containing liquid, the εolution or εuεpenεion, in for example propylene carbonate, vegetable oilε or triglycerideε, is preferably encapεulated in a gelatin capεule. Such eεter εolutionε, and the preparation and encapsulation thereof, are discloεed in U.S. Patentε Noε. 4,328,245; 4,409,239; and 4,410,545. For a liquid doεage form, the εolution, e.g. in a polyethylene glycol, may be diluted with a εufficient quantity of a pharmaceutically acceptable liquid carrier, e.g. water, to be eaεily meaεured for adminiεtration. Alternatively, liquid or semi-solid oral formulations may be prepared by diεsolving or dispersing the active compound or salt in vegetable oils, glycolε, triglycerideε, propylene glycol eεterε (e.g. propylene carbonate) and the like, and encapεulating these εolutionε or suspenεionε in hard or soft gelatin capsule εhellε. Other uεeful formulationε include thoεe εet forth in U.S. Patents Nos. Re. 28,819 and 4,358,603. Parenteral adminiεtration iε generally characterized by injection, either εubcutaneouεly, intramuεcularly or intravenouεly. Injectableε can be prepared in conventional formε, either as liquid solutions or suεpenεions, εolid forms suitable for solution or εuεpenεion in liquid prior to injection, or aε emulεionε. Suitable excipientε are, for example, water, εaline, dextroεe, glycerol, ethanol or the like. In addition, if desired, the pharmaceutical compositionε to be adminiεtered may alεo contain minor amountε of non-toxic auxiliary εubεtanceε εuch aε wetting or emulsifying agents, pH buffering agentε, εolubility enhancerε, and the like, εuch aε for example, εodium acetate, polyoxyethylene, εorbitan monolaurate, triethanolamine oleate, cyclodextrins, etc. A more recently deviεed approach for parenteral administration employε the implantation of a slow-release or suεtained-releaεe εyεtem, such that a constant level of dosage is maintained. See, e.g., U.S. Patent No. 3,710,795. The percentage of active compound contained in such parenteral compositions iε highly dependent on the specific nature thereof, as well as the activity of the compound and the needε of the εubject. However, percentageε of active ingredient of 0.01% to 10% in εolution are employable, and will be higher if the compoεition iε a εolid which will be subsequently diluted to the above percentages. Preferably the composition will comprise 0.2-2% of the active agent in solution. Formulations of the active compound or a εalt may also be administered to the respiratory tract as an aerosol or εolution for a nebulizer, or aε a microfine powder for inεufflation, alone or in combination with an inert carrier εuch as lactose. In such a caεe, the particleε of the formulation have diameterε of leεε than 50 micronε, preferably leεε than 10 micronε. EXAMPLES The following exampleε are given to enable thoεe εkilled in the art to more clearly underεtand and to practice the preεent invention. They εhould not be conεidered aε limiting the εcope of the invention, but merely aε being illuεtrative and repreεentative thereof. EXAMPLE 1 ■ Preparation of Compounds of Formula B IA. Formula B where Z* is a Side Chain of Formula ZA in which G is Methoxy. and Z' is Methyl. Z 2 . Z 3 , Z 4 are Hydrogen, and R is Tosyl p-Toluenesulfonyl chloride (30g) waε added to a εolution of methyl (E) 6- (l,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl) -4- methyl-4-hexenoate (40g) in pyridine (200ml) at 0°C. After 6 hourε the εolution waε poured on to ice and acidified to pH 3 with dilute hydrochloric acid. The εolution waε extracted with ethyl acetate and the extract was dried and evaporated to afford methyl (E) 6- (l,3-dihydro-6- methoxy-7-methyl-3-oxo-4-p-tolueneεulfonyloxyiεobenzofuran-5-yl) -4-methyl- 4-hexenoate. IB. Formula B varying Z* By following the procedure of part A and εubεtituting methyl (E) 6- (1,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl) -4- methyl-4-hexenoate with: methyl (E) -2- [2- [2- [1,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl] ethylidene] cyclopent-1-yl]acetate; methyl 3- (l,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5- iεobenzofuranylmethyl) -2-methylcyclopent-2-en-l-ylacetate; ethyl (E) -3- [2- (1,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl)ethylidene] cyclopentane-1-carboxylate; methyl (E) -2- [3- (4-hydroxy-l,3-dihydro-6-methoxy-7-methyl-3- oxoisobenzofuran-5-yl) -prop-1-en-l-yl] -3-methylbenzoate; methyl 4- (l,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-ylmethyl) -3-methylcyclopent-3-ene-1- carboxylate; methyl 3- [3- (l,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3- oxoisobenzofuran-5-yl) cyclopent-1-en-1-yl] -propionate; methyl (E) -2- [-3- (l,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl) -1-methylpropenyl] - cyclopentanecarboxylate; and the compoundε of Formula 1 where Z* correεpondε to the εide chainε identified in the following tableε: there are obtained methyl (E) -2- [2- [2- [l,3-dihydro-6-methoxy-7-methyl-3-oxo-4-p- toluenesulfonyloxyiεobenzofuran-5-yl]ethylidene] cyclopent-1- yl]acetate; methyl 3- (l,3-dihydro-6-methoxy-7-methyl-3-oxo-4-p- toluenesulfonyloxy-5-isobenzofuranylmethyl) -2-methylcyclopent- 2-en-1-ylacetate; ethyl (E) -3- [2- (l,3-dihydro-6-methoxy-7-methyl-3-oxo-4-p- toluenesulfonyloxyiεobenzofuran-5-yl)ethylidene] cyclopentane-1- carboxylate; methyl (E) -2- [3- (l,3-dihydro-6-methoxy-7-methyl-3-oxo-4-p- toluenesulfonyloxyisobenzofuran-5-yl) -prop-1-en-l-yl] -3- methylbenzoate; methyl 4- (l,3-dihydro-6-methoxy-7-methyl-3-oxo-4-p- toluenesulfonyloxyisobenzofuran-5-ylmethyl) -3-methylcyclopent- 3-ene-1-carboxylate; methyl 3- [3- (l,3-dihydro-6-methoxy-7-methyl-3-oxo-4-p- tolueneεulfonyloxyiεobenzo-furan-5-yl) cyclopent-1-en-l-yl] - propionate; methyl (E) -2- [-3- (l,3-dihydro-6-methoxy-7-methyl-3-oxo-4-p- tolueneεulfonyloxyiεobenzofuran-5-yl) -1-methylpropenyl] - cyclopentanecarboxylate; and the other correεponding compoundε of Formula B. EXAMPLE 2 Preparation of Compoundε of Formula C 2A. Formula C where Z b iε a Side Chain of Formula ZA in which z' is Methyl. Z 2 . Z 3 . and Z 4 are Hvdroσen. and R b is Toεyl A εolution of methyl (E) 6- (l,3-dihydro-6-methoxy-7-methyl-3-oxo-4-p- toluenesulfonyloxyisobenzofuran-5-yl) -4-methyl-4-hexenoate (28g) in 2,4,6- collidine (100ml) was heated to 65°C and lithium iodide (50g) waε added. After 3 dayε the solution was added to ethyl acetate and dilute hydrochloric acid. The organic layer waε dried and evaporated to afford (E) 6- (l,3-dihydro-6-hydroxy-7-methyl-3-oxo-4-p- tolueneεulfonyloxyiεobenzofuran-5-yl) -4-methyl-4-hexenoic acid. 2B. Formula C Varying Z b By following the procedure of part A and substituting methyl (E) 6- (1,3-dihydro-6-methoxy-7-methyl-3-oxo-4-p-tolueneεulfonyloxyiεobenzofuran- 5-yl) -4-methyl-4-hexenoate with: methyl (E) -2- [2- [2- [l,3-dihydro-6-methoxy-7-methyl-3-oxo-4-p- toluenesulfonyloxyiεobenzofuran-5-yl]ethylidene] cyclopent-1- yl]acetate; methyl 3- (l,3-dihydro-6-methoxy-7-methyl-3-oxo-4-p- toluenesulfonyloxyisobenzofuran-5-ylmethyl) -2-methylcyclopent- 2-en-1-ylacetate; ethyl (E) -3- [2- (1,3-dihydro-6-methoxy-7-methyl-3-oxo-4-p- toluenesulfonyloxyisobenzofuran-5-yl)ethylidene] cyclopentane-1- carboxylate; methyl (E) -2- [3- (l,3-dihydro-6-methoxy-7-methyl-3-oxo-4-p- tolueneεulfonyloxyiεobenzofuran-5-yl) -prop-1-en-l-yl] -3- methylbenzoate; methyl 4- (l,3-dihydro-6-methoxy-7-methyl-3-oxo-4-p- toluenesulfonyloxyisobenzofuran-5-ylmethyl) -3-methylcyclopent- 3-ene-1-carboxylate; methyl 3- [3- (l,3-dihydro-6-methoxy-7-methyl-3-oxo-4-p- tolueneεulfonyloxyiεobenzofuran-5-yl) cyclopent-1-en-l-yl] - propionate; methyl (E) -2- [-3- (l,3-dihydro-6-methoxy-7-methyl-3-oxo-4-p- tolueneεulfonyloxyiεobenzofuran-5-yl) -1-methylpropenyl] - cyclopentanecarboxylate; and the other compoundε of Formula B correεponding to thoεe liεted in the tableε in Example IB, there are obtained: (E) -2- [2- [2- [1,3-dihydro-6-hydroxy-7-methyl-3-oxo-4-p- tolueneεulfonyloxyiεobenzofuran-5-yl]ethylidene] cyclopent-1- yl]acetic acid; 3- (1,3-dihydro-6-hydroxy-7-methyl-3-oxo-4-p-toluenesulfonyl- oxyisobenzofuran-5-ylmethyl) -2-methylcyclopent-2-en-1-ylacetic acid; (E) -3- [2- (l,3-dihydro-6-hydroxy-7-methyl-3-oxo-4-p-toluene- εulfonyloxyiεobenzofuran-5-yl)ethylidene] cyclopentane-1- carboxylic acid; (E) -2- [3- (l,3-dihydro-6-hydroxy-7-methyl-3-oxo-4-p- tolueneεulfonyloxyisobenzofuran-5-yl) -prop-1-en-l-yl] -3- methylbenzoic acid; 4- (l,3-dihydro-6-hydroxy-7-methyl-3-oxo-4-p-tolueneεulfonyl- •. oxyiεobenzofuran-5-ylmethyl) -3-methylcyclopent-3-ene-l- carboxylic acid; 3- [3- (l,3-dihydro-6-hydroxy-7-methyl-3-oxo-4-p- toluenesulfonyloxyiεobenzofuran-5-yl) cyclopent-1-en-1-yl] - propionic acid; (E) -2- [-3- (l,3-dihydro-6-hydroxy-7-methyl-3-oxo-4-p- tolueneεulfonyloxyiεobenzofuran-5-yl) -1-methylpropenyl] - cyclopentanecarboxylic acid; and the other compounds of Formula C corresponding to thoεe liεted in the tables in Example IB. EXAMPLE 3 Preparation of Compounds of Formula D 3A. Formula D where Z* is a Side Chain of Formula ZA in which z' is Methyl. Z 2 . Z 3 . Z 4 are Hydrogen. G is Methoxy. and R b iε Tosyl A εolution of (E) 6- (l,3-dihydro-6-hydroxy-7-methyl-3-oxo-4-p- tolueneεulfonyloxyiεobenzofuran-5-yl) -4-methyl-4-hexenoic acid (23g) and p-tolueneεulfonic acid (0.8g) in methanol (150ml) waε εtirred for 18 hourε then added to water and ethyl acetate. The organc layer waε dried and evaporated and the reεidue waε chromatographed on εilica gel, eluting with hexane:ethyl acetate: methanol 40:58:2, to afford methyl (E) 6- (1,3- dihydro-6-hydroxy-7-methyl-3-oxo-4-p-tolueneεulfonyloxyiεobenzofuran-5-yl) - 4-methyl-4-hexenoate. 3B. Formula D Varying Z* By following the procedure of part A and εubεtituting (E) 6- (1,3- dihydro-6-hydroxy-7-methyl-3-oxo-4-p-tolueneεulfonyloxyiεobenzofuran-5-yl) - 4-methyl-4-hexenoic acid with: (E) -2- [2- [2- [l,3-dihydro-6-hydroxy-7-methyl-3-oxo-4-p- toluenesulfonyloxyisobenzofuran-5-yl] ethylidene] cyclopent-1- yl]acetic acid; 3- (1,3-dihydro-6-hydroxy-7-methyl-3-oxo-4-p-toluenesulfonyl- oxyisobenzofuran-5-ylmethyl) -2-methylcyclopent-2-en-1-ylacetic acid; (E) -3- [2- (l,3-dihydro-6-hydroxy-7-methyl-3-oxo-4-p-toluene- εulfonyloxyiεobenzofuran-5-yl)ethylidene] cyclopentane-l- carboxylic acid; (E) -2- [3- (l,3-dihydro-6-hydroxy-7-methyl-3-oxo-4-p- tolueneεulfonyloxyiεobenzofuran-5-yl) -prop-1-en-l-yl] -3- methylbenzoic acid; 4- (l,3-dihydro-6-hydroxy-7-methyl-3-oxo-4-p-tolueneεulfonyl- oxyiεobenzofuran-5-ylmethyl) -3-methylcyclopent-3-ene-1- carboxylic acid; 3- [3- (l,3-dιhydro-6-hydroxy-7-methyl-3-oxo-4-p- toluenesulfonyloxyisobenzofuran-5-yl) cyclopent-1-en-l-yl] - propionic acid; (E) -2- [-3- (l,3-dihydro-6-hydroxy-7-methyl-3-oxo-4-p- ■• toluenesulfonyloxyisobenzofuran-5-yl) -1-methylpropenyl] - cyclopentanecarboxylic acid; and the other compoundε of Formula C correεponding to thoεe liεted in the tables in Example IB, there are obtained: methyl (E) -2- [2- [2- [l,3-dihydro-6-hydroxy-7-methyl-3-oxo-4-p- tolueneεulfonyloxyiεobenzofuran-5-yl]ethylidene]cyclopent-1- yl]acetate; methyl 3- (l,3-dihydro-6-hydroxy-7-methyl-3-oxo-4-p- tolueneεulfonyloxy-5-iεobenzofuranylmethyl) -2-methylcyclopent- 2-en-1-ylacetate; methyl (E) -3- [2- (l,3-dihydro-6-hydroxy-7-methyl-3-oxo-4-p- tolueneεulfonyloxyiεobenzofuran-5-yl)ethylidene] cyclopentane-1- carboxylate; methyl (E) -2- [3- (l,3-dihydro-6-hydroxy-7-methyl-3-oxo-4-p- toluenesulfonyloxyiεobenzofuran-5-yl) -prop-1-en-l-yl] -3- methylbenzoate; methyl 4- (l,3-dihydro-6-hydroxy-7-methyl-3-oxo-4-p- tolueneεulfonyloxyiεobenzofuran-5-ylmethyl) -3-methylcyclopent- 3-ene-1-carboxylate; methyl 3- [3- (1,3-dihydro-6-hydroxy-7-methyl-3-oxo-4-p- tolueneεulfonyloxyiεobenzofurc_n-5-yl) cyclopent-1-en-1-yl] - propionate; methyl (E) -2- [-3- (l,3-dihydro-6-hydroxy-7-methyl-3-oxo-4-p- toluenesulfonyloxyisobenzofuran-5-yl) -1-methylpropenyl] - cyclopentanecarboxylate; and the other compounds of Formula D corresponding to thoεe liεted in the tables in Example IB. EXAMPLE 4 Preparation of Coπrpoundε of Formula E 4A. Formula E where Z* iε a Side Chain of Formula ZA. in which Z' iε Methyl. Z 2 . Z 3 . and Z 4 are Hydrogen. G is Methoxy. and R b is Tosyl Trifluoromethanesulfonic anhydride (10.57g) waε added to a εolution of methyl (E) 6- (l,3-dihydro-6-hydroxy-7-methyl-3-oxo-4-p- tolueneεulfonyloxyiεobenzofuran-5-yl) -4-methyl-4-hexenoate in methylene chloride (500ml) amd pyridine (5ml) at 0°C. After 6 hourε the reaction was added to exceεε aqueouε εodium bicarbonate. The organic εolution waε dried and evaporated to afford methyl (E) 6- (l,3-dihydro-7-methyl-3-oxo-4-p- tolueneεulfonyloxy-6-trifluoromethaneεulfonyloxyiεobenzofuran-5-yl) -4- methyl-4-hexenoate. 4B. Formula E Varying Z* By following the procedure of part A and εubεtituting methyl (E) 6- (1,3-dihydro-6-hydroxy-7-methyl-3-oxo-4-p-tolueneεulfonyloxyiεobenzofuran- 5-yl) -4-methyl-4-hexenoate with: methyl (E) -2- [2- [2- [1,3-dihydro-6-hydroxy-7-methyl-3-oxo-4-p- toluenesulfonyloxyiεobenzofuran-5-yl] ethylidene] cyclopent-1- •' yl]acetate; methyl 3- (1,3-dihydro-6-hydroxy-7-methyl-3-oxo-4-p- toluenesulfonyloxyisobenzofuran-5-ylmethyl) -2-methylcyclopent- 2-en-1-ylacetate; methyl (E) -3- [2- (l,3-dihydro-6-hydroxy-7-methyl-3-oxo-4-p- tolueneεulfonyloxyiεobenzofuran-5-yl)ethylidene] cyclopentane-1- carboxylate; methyl (E) -2- [3- (1,3-dihydro-6-hydroxy-7-methyl-3-oxo-4-p- tolueneεulfonyloxyisobenzofuran-5-yl) -prop-1-en-l-yl] -3- methylbenzoate; methyl 4- (l,3-dihydro-6-hydroxy-7-methyl-3-oxo-4-p- toluenesulfonyloxyiεobenzofuran-5-ylmethyl) -3-methylcyclopent- 3-ene-1-carboxylate; methyl 3- [3- (l,3-dihydro-6-hydroxy-7-methyl-3-oxo-4-p- toluenesulfonyloxyiεobenzofuran-5-yl) cyclopent-1-en-l-yl] - propionate; methyl (E) -2- [-3- (l,3-dihydro-6-hydroxy-7-methyl-3-oxo-4-p- tolueneεulfonyloxyisobenzofuran-5-yl) -1-methylpropenyl] - cyclopentanecarboxylate; and the other compoundε of Formula D correεponding to thoεe liεted in the tableε in Example IB, there are obtained: methyl (E) -2- [2- [2- [1,3-dihydro-7-methyl-3-oxo-4-p- tolueneεulfonyloxy-6-trifluoromethanesulfonyloxy-isobenzofuran- 5-yl]ethylidene] cyclopent-1-yl]acetate; methyl 3- (l,3-dihydro-7-methyl-3-oxo-4-p-toluenesulfonyl-oxy-6- trifluoromethaneεulfonyloxyisobenzo-furan-5-ylmethyl) -2- methylcyclopent-2-en-1-ylacetate; methyl (E) -3- [2- (l,3-dihydro-7-methyl-3-oxo-4-p-toluene-sulfonyloxy- 6-trifluoromethanesulfonyloxyisobenzofuran-5- yl)ethylidene]cyclopentane-1-carboxylate; methyl (E)-2- [3- (l,3-dihydro-7-methyl-3-oxo-4-p-tolueneεulfonyloxy-6- trifluoromethaneεulfonyloxy-iεobenzofuran-5-yl) -prop-1-en-1- yl] -3-methylbenzoate; methyl 4- (l,3-dihydro-7-methyl-3-oxo-4-p-tolueneεulfonyl-oxy-6- trifluoromethaneεulfonyloxyiεobenzofuran-5-ylmethyl) -3- methylcyclopent-3-ene-1-carboxylate; methyl 3- [3- (l,3-dihydro-7-methyl-3-oxo-4-p-toluenesulfonyloxy-6- trifluoromethaneεulfonyloxy-iεobenzofuran-5-yl)cyclopent-1-en- 1-yl] -propionate; methyl (E) -2- [-3- (1,3-dihydro-7-methyl-3-oxo-4-p-tolueneεulfonyloxy- 6-trifluoromethanesulfonyloxy-isobenzofuran-5-yl) -1- methylpropenyl] -cyclopentanecarboxylate; and the other compounds of Formula E corresponding to those liεted in the tables in Example IB. EXAMPLE 5 Preparation of Compounds of Formula F 5A. Formula F where Z* is a Side Chain of Formula ZA. in which z' is Methyl. Z 2 . Z 3 . and Z 4 are Hydrogen. G is Methoxy. R is Tosyl, and R 7 is Vinyl A mixture of lithium chloride (4.8g), tris (dibenzylideneacetone) - dipalladium (0) chloroform adduct (0.65g), triphenylarεine (1.6g) and methyl (E) 6- (l,3-dihydro-7-methyl-3-oxo-4-p-tolueneεulfonyloxy-6- trifluoromethaneεulfonyloxyiεobenzofuran-5-yl) -4-methyl-4-hexenoate (24.2g) in N-methylpyrrolidinone (220ml) waε heated to 55°C. Vinyltributyltin (15g) waε added. After 3 hourε the mixture waε added to water (500ml) , potassium fluoride (16g) and ethyl acetate. The organic solution was dried, filtered through celite and evaporated to afford methyl (E) 6- (1,3- dihydro-7-methyl-3-oxo-4-p-toluenesulfonyloxy-6-vinyliBObenzofuran-5-yl) -4- methyl-4-hexenoate. 5B. Formula F Varying Z* By following the procedure of part A and subεtituting methyl (E) 6- (1,3-dihydro-7-methyl-3-oxo-4-p-toluenesulfonyloxy-6- trifluoromethaneεulfonyloxyiεobenzofuran-5-yl) -4-methyl-4-hexenoate with: methyl (E) -2- [2- [2- [l,3-dihydro-7-methyl-3-oxo-4-p- tolueneεulfonyloxy-6-trifluoromethaneεulfonyloxy-isobenzofuran- 5-yl]ethylidene]cyclopent-1-yl]acetate; methyl 3- (l,3-dihydro-7-methyl-3-oxo-4-p-toluenesulfonyl-oxy-6- trifluoromethanesulfonyloxyisobenzo-furan-5-ylmethyl) -2- methylcyclopent-2-en-1-ylacetate; methyl (E) -3- [2- (l,3-dihydro-7-methyl-3-oxo-4-p-toluene-sulfonyloxy- 6-trifluoromethaneεulfonyloxyiεobenzofuran-5- yl)ethylidene] cyclopentane-1-carboxylate; methyl (E) -2- [3- (l,3-dihydro-7-methyl-3-oxo-4-p-tolueneεulfonyloxy-6- trifluoromethaneεulfonyloxy-iεobenzofuran-5-yl) -prop-1-en-1- yl] -3-methylbenzoate; methyl 4- (l,3-dihydro-7-methyl-3-oxo-4-p-tolueneεulfonyl-oxy-6- trifluoromethanesulfonyloxyisobenzofuran-5-ylmethyl) -3- methylcyclopent-3-ene-1-carboxylate; methyl 3- [3- (l,3-dihydro-7-methyl-3-oxo-4-p-toluenesulfonyloxy-6- trifluoromethaneεulfonyloxy-isobenzofuran-5-yl) cyclopent-1-en- 1-yl] -propionate; methyl (E) -2- [-3- (l,3-dihydro-7-methyl-3-oxo-4-p-toluenesulfonyloxy- 6-trifluoromethaneεulfonyloxy-iεobenzofuran-5-yl) -1- methylpropenyl] -cyclopentanecarboxylate; and the other compoundε of Formula E corresponding to those listed in the tables in Example IB, there are obtained: methyl (E) -2- [2- [2- [1,3-dihydro-7-methyl-3-oxo-4-p- tolueneεulfonyloxy-6-vinyliεobenzofuran-5- ' yl]ethylidene] cyclopent-1-yl]acetate; methyl 3- (l,3-dihydro-7-methyl-3-oxo-4-p-toluenesulfonyl-oxy-6- vinyliεobenzofuran-5-ylmethyl) -2-methylcyclopent-2-en-1- ylacetate; methyl (E) -3- [2- (1,3-dihydro-7-methyl-3-oxo-4-p-tolueneεulfonyloxy-6- vinyliεobenzofuran-5-yl)ethylidene] cyclopentane-1-carboxylate,- methyl (E) -2- [3- (1,3-dihydro-7-methyl-3-oxo-4-p-toluenesulfonyloxy-6- vinylisobenzofuran-5-yl) -prop-1-en-l-yl] -3-methylbenzoate; methyl 4- (l,3-dihydro-7-methyl-3-oxo-4-p-toluenesulfonyl-oxy-6- vinyliεobenzofuran-5-ylmethyl) -3-methylcyclopent-3-ene-1- carboxylate; methyl 3- [3- (1,3-dihydro-7-methyl-3-oxo-4-p-toluenesulfonyloxy-6- vinyliεobenzofuran-5-yl) cyclopent-1-en-l-yl] -propionate; methyl (E) -2- [-3- (1,3-dihydro-7-methyl-3-oxo-4-p-toluenesulfonyloxy- 6-vinylisobenzofuran-5-yl) -1-methylpropenyl] - cyclopentanecarboxylate; and the other compoundε of Formula F correεponding to thoεe liεted in the tables in Example IB. 5C. Formula F Varying R 7 By following the procedure of part A and substituting vinyltributyltin with: methyltributyltin; cyclopropyltributyltin; fluorovinyltributyltin; trifluorovinyltributyltin; prop-2-enyltributyltin; . , ethynyltributyltin; pent-2-ynyltributyltin; allyltributyltin; and 4-methoxybenzyloxymethyltributyltin; there are obtained: methyl (E) 6- (1,3-dihydro-6,7-dimethyl -3-oxo-4-p- tolueneεulfonyloxyiεobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) 6- (6-cyclopropyl-l,3-dihydro-7-methyl-3-oxo-4-p- tolueneεulfonyloxyisobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) 6- (1,3-dihydro-6-fluorovinyl-7-methyl-3-oxo-4-p- tolueneεulfonyloxyiεobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) 6- (1,3-dihydro-7-methyl-3-oxo-4-p-tolueneεulfonyloxy-6- trifluorovinyliεobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) 6- (l,3-dihydro-7-methyl-3-oxo-6- (prop-2-enyl) -4-p- tolueneεulfonyloxyiεobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) 6- (l,3-dihydro-6-ethynyl-7-methyl-3-oxo-4-p- toluenesulfonyloxyisobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) 6- (l,3-dihydro-7-methyl-3-oxo-6- (pent-2-ynyl) -4-p- toluenesulfonyloxyisobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) 6- (6-allyl-l,3-dihydro-7-methyl-3-oxo-4-p- toluenesulfonyloxyisobenzofuran-5-yl) -4-methyl-4-hexenoate; and methyl (E) 6- (l,3-dihydro-6-methoxybenzyloxymethyl-7-methyl-3-oxo-4- p-tolueneεulfonyloxyiεobenzofuran-5-yl) -4-methyl-4-hexenoate. EXAMPLE 6 Alternative Preparation of Compoundε of Formula F 6A. Formula F where Z* iε a Side Chain of Formula ZA. in which Z' iε Methyl. Z 2 . Z 3 . and Z 4 are Hydrogen. G is Methoxy. R is Tosyl■ and R 7 is Ethyl A solution of methyl (E) 6- (1,3-dihydro-7-methyl-3-oxo-4-p- tolueneεulfonyloxy-6-vinyliεobenzofuran-5-yl) -4-methyl-4-hexenoate (17.7g) and triε (triphenylphosphine) rhodium chloride (1.2g) in benzene (180ml) and ethanol (180ml) was hydrogenated for 11 hourε. The εolventε were removed under vacuum and the reεidue waε cryεtallized from ethyl acetate/tert butyl methyl ether to afford methyl (E) 6- (l,3-dihydro-6-ethyl-7-methyl-3-oxo-4- p-tolueneεulfonyloxyiεobenzofuran-5-yl) -4-methyl- -hexenoate, mp 101.3- 102.8°C. 6B. Formula F where R 7 is Ethyl. Varying Z* By following the procedure of part A and εubεtituting methyl (E) 6- (1,3-dihydro-7-methyl-3-oxo-4-p-tolueneεulfonyloxy-6-vinyliεobenzofuran-5- yl) -4-methyl-4-he:_enoate with: methyl (E) -2- [2- [2- [1,3-dihydro-7-methyl-3-oxo-4-p- tolueneεulfonyloxy-6-vinyliεobenzofuran-5- yl]ethylidene]cyclopent-1-yl]acetate; methyl 3- (l,3-dihydro-7-methyl-3-oxo-4-p-toluenesulfonyl-oxy-6- vinylisobenzofuran-5-ylmethyl) -2-methylcyclopent-2-en-l- ylacetate; methyl (E) -3- [2- (l,3-dihydro-7-methyl-3-oxo-4-p-toluenesulfonyloxy-6- vinyliεobenzofuran-5-yl)ethylidene] cyclopentane-1-carboxylate; methyl (E) -2- [3- (l,3-dihydro-7-methyl-3-oxo-4-p-tolueneεulfonyloxy-6- vinylisobenzofuran-5-yl) -prop-1-en-1-yl] -3-methylbenzoate; methyl 4- (l,3-dihydro-7-methyl-3-oxo-4-p-toluenesulfonyloxy-6- vinylisobenzofuraui-5-ylmethyl) -3-methylcyclopent-3-ene-1- carboxylate; methyl 3- [3- (l,3-dihydro-7-methyl-3-oxo-4-p-toluenesulfonyloxy-6- vinylisobenzofuran-5-yl) cyclopent-1-en-1-yl] -propionate; methyl (E) -2- [-3- (1,3-dihydro-7-methyl-3-oxo-4-p-toluenesulfonyloxy- 6-vinylisobenzofuran-5-yl) -1-methylpropenyl] - cyclopentanecarboxylate; and the other compounds of Formula F correεponding to thoεe liεted in the tableε in Example IB, there are obtained: methyl (E) -2- [2- [2- [l,3-dihydro-6-ethyl-7-_nethyl-3-oxo-4-p- tolueneεulfonyloxyiεobenzofuran-5-yl]ethylidene] cyclopent-1- yl]acetate; methyl 3- (l,3-dihydro-6-ethyl-7-methyl-3-oxo-4-p- tolueneεulfonyloxyiεobenzofuran-5-ylmethyl) -2-methylcyclopent- 2-en-1-ylacetate; methyl (E) -3- [2- (l,3-dihydro-6-ethyl-7-methyl-3-oxo-4-p- tolueneεulfonyloxyiεobenzofuran-5-yl)ethylidene] cyclopentane-1- carboxylate; methyl (E) -2- [3- (1,3-dihydro-6-ethyl-7-methyl-3-oxo-4-p- toluenesulfonyloxyisobenzofuran-5-yl) -prop-1-en-l-yl] -3- methylbenzoate; methyl 4- (l,3-dihydro-6-ethyl-7-methyl-3-oxo-4-p- toluenesulfonyloxyisobenzofur_ιn-5-ylmethyl) -3-methylcyclopent- 3-ene-1-carboxylate; methyl 3- [3- (l,3-dihydro-6-ethyl-7-methyl-3-oxo-4-p- tolueneεulfonyloxyiεobenzofurεu_-5-yl) cyclopent-1-en-1-yl] - propionate; methyl (E) -2- [-3- (l,3-dihydro-6-ethyl-7-methyl-3-oxo-4-p- tolueneεulfonyloxyiεobenzofuran-5-yl) -1-methylpropenyl] - cyclopentanecarboxylate; and the other compoundε of Formula F where R 7 iε ethyl, correεponding to thoεe listed in the tableε in Example IB. EXAMPLE 7 Preparation of Co poundε of Formula A 7A. Formula A where Z b iε a Side Chain of Formula ZA, in which Z' iε Methyl. Z 2 . Z 3 . and Z 4 are Hydrogen, and R 7 is Vinyl A solution of methyl (E) 6- (l,3-dihydro-7-methyl-3-oxo-4-p- tolueneεulfonyloxy-6-vinyliεobenzofuran-5-yl) -4-methyl-4-hexenoate (0.37g) and lithium hydroxide (0.4g) in methanol (6ml) and water (6ml) waε heated at 62°C for 15 hourε. The reaction waε acidified with aqueouε εodium hydrogen εulfate and extracted with ethyl acetate. The extract waε dried and evaporated and the residue chromatographed on silica gel, eluting with ethyl acetate/hexane/acetic acid to give (E) 6- (1,3-dihydro-4-hydroxy-7- methyl-3-oxo-6-vinyliεobenzofuran-5-yl) -4-methyl-4-hexenoic acid, m.p. 148-149°C (tert-butylmethyl ether/hexane) . 7B. Formula A Varying Z* By following the procedure of part A and εubstituting methyl (E) 6- (1,3-dihydro-7-methyl-3-oxo-4-p-tolueneεulfonyloxy-6-vinyliεobenzofuran-5- yl) -4-methyl-4-hexenoate with: methyl (E) -2- [2- [2- [l,3-dihydro-7-methyl-3-oxo-4-p- tolueneεulfonyloxy-6-vinylisobenzofuran-5- yl]ethylidene]cyclopent-1-yl]acetate; methyl 3- (l,3-dihydro-7-methyl-3-oxo-4-p-toluenesulfonyl-oxy-6- vinylisobenzofuran-5-ylmethyl) -2-methylcyclopent-2-en-1- ylacetate; methyl (E) -3- [2- (l,3-dihydro-7-methyl-3-oxo-4-p-toluenesulfonyloxy-6- vinyliεobenzofuran-5-yl)ethylidene] cyclopentane-1-carboxylate; methyl (E) -2- [3- (1,3-dihydro-7-methyl-3-oxo-4-p-tolueneεulfonyloxy-6- vinylisobenzofuran-5-yl) -prop-1-en-1-yl] -3-methylbenzoate; methyl 4- (l,3-dihydro-7-methyl-3-oxo-4-p-tolueneεulfonyl-oxy-6- vinyliεobenzofuran-5-ylmethyl) -3-methylcyclopent-3-ene-1- carboxylate; methyl 3- [3- (1,3-dihydro-7-methyl-3-oxo-4-p-toluenesulfonyloxy-6- vinyliεobenzofuran-5-yl) cyclopent-1-en-l-yl] -propionate; methyl (E) -2- [-3- (l,3-dihydro-7-methyl-3-oxo-4-p-tolueneεulfonyloxy- 6-vinyliεobenzofuran-5-yl) -1-methylpropenyl] - cyclopentanecarboxylate; and the other compoundε of Formula F correεponding to those liεted in the tableε in Example IB, there are obtained: (E) -2- [2- [2 [1,3-dihydro-4-hydroxy-7-methyl-3-oxo-6- vinylisobenzofuran-5-yl] ethylidene] cyclopent-1-yl]acetic acid; 3- (1,3-dihydro-4-hydroxy-7-methyl-3-oxo-6-vinylisobenzofuran-5- ylmethyl) -2-methylcyclopent-2-en-l-ylacetic acid; (E) -3- [2- (l,3-dihydro-4-hydroxy-7-methyl-3-oxo-6-vinylisobenzofuran- 5-yl)ethylidene] cyclopentane-1-carboxylic acid; (E) -2- [3- (l,3-dihydro-4-hydroxy-7-methyl-3-oxo-6-vinyliεobenzofuran- 5-yl) -prop-1-en-1-yl] -3-methylbenzoic acid; 4- (1,3-dihydro-4-hydroxy-7-methyl-3-oxo-6-vinylisobenzofuran-5- ylmethyl) -3-methylcyclopent-3-ene-l-carboxylic acid; 3- [3- (l,3-dihydro-4-hydroxy-7-methyl-3-oxo-6-vinyliεobenzo-fur__n-5- yl)cyclopent-1-en-l-yl] -propionic acid; (E) -2- [-3- (l,3-dihydro-4-hydroxy-7-methyl-3-oxo-6-vinyliεobenzofuran- 5-yl) -1-methylpropenyl] -cyclopentanecarboxylic acid; and the other compoundε of Formula A where R 7 iε vinyl, corresponding to thoεe liεted in the tables that follow: 7C. Formula A Varying R 7 By following the procedure of part A and subεtituting methyl (E) 6- (1,3-dihydro-7-methyl-3-oxo-4-p-tolueneεulfonyloxy-6-vinyliεobenzofuran-5- yl) -4-methyl-4-hexenoate with: methyl (E) 6- (l,3-dihydro-6,7-dimethyl-3-oxo-4-p- toluenesulfonyloxyisobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) 6- (l,3-dihydro-6-ethyl-7-methyl-3-oxo-4-p- toluenesulfonyloxyisobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) 6- (6-cyclopropyl-l,3-dihydro-7-methyl-3-oxo-4-p- tolueneεulfonyloxyiεobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) 6- (l,3-dihydro-6-fluorovinyl-7-methyl-3-oxo-4-p- tolueneεulfonyloxyiεobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) 6- (l,3-dihydro-7-methyl-3-oxo-4-p-tolueneεulfonyloxy-6- trifluorovinyliεobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) 6- (1,3-dihydro-7-methyl-3-oxo-6- (prop-2-enyl) -4-p- tolueneεulfonyloxyiεobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) 6- (1,3-dihydro-6-ethynyl-7-methyl-3-oxo.-4-p- tolueneεulfonyloxyiεobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) 6- (1,3-dihydro-7-methyl-3-oxo-6- (pent-2-ynyl) -4-p- tolueneεulfonyloxyiεobenzofuran-5-yl) - -methyl-4-hexenoate; methyl (E) 6- (6-allyl-l,3-dihydro-7-methyl-3-oxo-4-p- toluenesulfonyloxyiεobenzofuran-5-yl) -4-methyl-4-hexenoate; an methyl (E) 6- (l,3-dihydro-6- (4-methoxybenzyloxymethyl) -7-methyl-3- oxo-4-p-tolueneεulfonyloxyiεobenzofuran-5-yl) -4-methyl-4- hexenoate. there are obtained: (E) 6- (1,3-dihydro-4-hydroxy-6,7-dimethyl-3-oxoisobenzofuran-5-yl) -4- methyl-4-hexenoic acid; (E) 6- (1,3-dihydro-6-ethyl-4-hydroxy-7-methyl-3-oxoisobenzofuran-5- • • yl) -4-methyl-4-hexenoic acid; (E) 6- (6-cyclopropyl-l,3-dihydro-4-hydroxy-7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoic acid; (E) 6- (l,3-dihydro-6-fluorovinyl-4-hydroxy-7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoic acid; (E) 6- (l,3-dihydro-4-hydroxy-7-methyl-3-oxo-6- trifluorovinyliεobenzofuran-5-yl) -4-methyl-4-hexenoic acid; (E) 6- (l,3-dihydro-4-hydroxy-7-methyl-3-oxo-6- (prop-2- enyl)iεobenzofuran-5-yl) -4-methyl-4-hexenoic acid; (E) 6- (1,3-dihydro-6-ethynyl-4-hydroxy-7-methyl-3-oxoiεobenzofuran-5- yl) -4-methyl-4-hexenoic acid; (E) 6- (l,3-dihydro-4-hydroxy-7-methyl-3-oxo-6- (pent-2- ynyl)iεobenzofuran-5-yl) -4-methyl-4-hexenoic acid; (E) 6- (6-allyl-1,3-dihydro- -hydroxy-7-methyl-3-oxoiεobenzofuran-5- yl) -4-methyl-4-hexenoic acid; and (E) 6- (1,3-dihydro- -hydroxy-6- (4-methoxybenzyloxymethyl) -7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate. EXAMPLE 9 Preparation of Compoundε of Formula A where R 7 is Hvdroxymethyl and Foπrtyl 9A. Preparation of Methyl (E) 6- (1.3-dihvdro-6- (4-methoχybenzyl- oxymethyl) -7-methyl-3-oxo-4-p-toluenesulfonyloxyiso-benzofuran-5-yl) - 4-methyl-4-hexenoate A mixture of lithium chloride (1.6g), triε (dibenzylideneacetone) - dipalladium (0) chloroform adduct (0.22g), triphenylarεine (0.53g), methyl (E) 6- (l,3-dihydro-7-methyl-3-oxo-4-p-toluenesulfonyloxy-6- trifluoromethaneεulfonyloxy-iεobenzofuran-5-yl) -4-methyl-4-hexenoate (8.0g) and N-methylpyrrolidinone (70ml) iε heated to 55 β C. p-Methoxybenzyloxymethyltributyltin (7.5g) iε added. After 3 hourε the εolution iε added to water (200ml), potaεsium fluoride (5g) and ethyl acetate (200ml) . The organic εolution is dried, filtered through celite and evaporated, and the residue is chromatographed on εilica gel, eluting with hexane:ethyl acetate, to afford methyl (E) 6- (l,3-dihydro-6- (4- methoxybenzyloxymethyl) -7-methyl-3-oxo-4-p-toluenesulfonyloxyisobenzofuran- 5-yl) -4-methyl-4-hexenoate. 9B. Methyl (E) 6- (1.3-dihvdro-6-hvdroxymethyl-7-methyl-3-oxo-4- p-toluenesulfonyloxyisobenzofuran-5-yl) -4-methyl-4-hexenoate Methyl (E) 6- (1,3-dihydro-6- (4-methoxybenzyloxymethyl) -7-methyl-3- oxo-4-p-tolueneεulfonyloxyiεobenzofuran-5-yl) -4-methyl-4-hexenoate (0.5g) is dissolved in trifluoroacetic acid (10ml) at 0°C. After 30 minutes the solvent iε removed under vacuum and the reεidue iε chromatographed on silica gel, eluting with hexane:ethyl acetate, to afford methyl (E) 6- (1,3-dihydro-6-hydroxymethyl-7-methyl-3-oxo-4-p-toluenesulfonyl¬ oxyiεobenzofuran-5-yl) -4-methyl-4-hexenoate. 9C. Methyl (E) 6- (1.3-dihvdro-6-foππyl-7-methyl-3-oxo-4- p-toluenesulfonyloxyisobenzofuran-5-yl) -4-methyl-4-hexenoate Methyl (E) 6- (1,3-dihydro-6-hydroxymethyl-7-methyl-3-oxo-4- p-tolueneεulfonyloxyiεobenzofuran-5-yl) -4-methyl-4-hexenoate (0.2g) iε diεεolved in dichloromethane (10ml) and pyridinium chlorochromate (0.15g) iε added. After one hour water (25ml) iε added. The organic εolution iε dried and evaporated and the reεidue iε chromatographed on εilica gel, eluting with hexane:ethyl acetate, to afford methyl (E) 6- (1,3-dihydro-6- formyl-7-methyl-3-oxo-4-p-toluenesulfonyloxyiεobenzofuran-5-yl) -4-methyl-4- hexenoate. 9D. Formula A where R 7 iε 4-methoxybenzyloxymethyl. Hydroxymethyl and Formyl By following the procedureε of Exampleε 5 and 6 and εubεtituting methyl (E) 6- (1,3-dihydro-7-methyl-3-oxo-4-p-tolueneεulfonyloxy-6- trifluoromethaneεulfonyloxyiεobenzofuran-5-yl) -4-methyl-4-hexenoate with: methyl (E) 6- (1,3-dihydro-6- (4-methoxybenzyloxymethyl) -7-methyl-3- oxo-4-p-tolueneεulfonyloxyiεobenzofuran-5-yl) -4-methyl-4- hexenoate; methyl (E) 6- (1,3-dihydro-6-hydroxymethyl-7-methyl-3-oxo-4-p- tolueneεulfonyloxyiεobenzofuran-5-yl) -4-methyl-4-hexenoate; and methyl (E) 6- (1,3-dihydro-6-formyl-7-methyl-3-oxo-4-p- toluenesulfonyloxyisobenzofuran-5-yl) -4-methyl-4-hexenoate, there are obtained: (E) 6- (1,3-dihydro-6- (4-methoxybenzyloxymethyl) -7-methyl-3-oxo-4-p- tolueneεulfonyloxyiεobenzofuran-5-yl) -4-methyl-4-hexenoic acid; (E) 6- (l,3-dihydro-6-hydroxymethyl-7-methyl-3-oxo-4-p- toluenesulfonyloxyisobenzofuran-5-yl) -4-methyl-4-hexenoic acid; and (E) 6- (l,3-dihydro-6-foππyl-7-methyl-3-oxo-4-p- tolueneεulfonyloxyiεobenzofuran-5-yl) -4-methyl-4-hexenoic acid. EXAMPLE 10 Preparation of Compoundε of Formula 2 10A. Preparation of 2 where Z is ZA. in which Z' is Methyl. Z 2 . Z 3 . and Z 4 are Hydrogen. R 7 is Ethyl, and G iε Methoxy To a 0°C solution of 4.59 g of methyl (E) -6- (l,3-dihydro-4-hydroxy-6- ethyl-7-methyl-3-oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate and 2.22 ml of pyridine in 100 ml of methylene chloride iε added 2.55 ml of trifluoromethane εulfonic anhydride dropwiεe. After 30 minuteε, the reaction mixture iε poured into IN aqueouε εodium hydrogen εulfate. Thiε mixture iε extracted with dichloromethane, and the organic phase further washed with water and brine. The organic phase is dried over magneεium εulfate and concentrated under reduced preεεure, to give methyl (E)-6-(l,3- dihydro-6-ethyl-7-methyl-4-trifluoromethylεulfonyloxy-3-oxoiεobenzofuran-5- yl) -4-methyl-4-hexenoate. 10B. Preparation of 2, varying R 7 Similarly, following the procedures of Example 10A above, but replacing methyl (E) -6- (1,3-dihydro-4-hydroxy-6-ethyl-7-methyl-3- oxoisobenzofuran-5-yl) -4-methyl-4-hexenoate with other compoundε of Formula A, the following intermediateε of Formula 2 are prepared: methyl (E) -6- (l,3-dihydro-6-ethyl-7-methyl-3-oxo-4- trifluoromethylεulfonyloxyiεobenzofuran-5-yl) -3,4-dimethyl-4- hexenoate; and methyl (E) -2-{2- [2- (1,3-dihydro-6-ethyl-7-methyl-3-oxo-4- trifluoromethylεulfonyloxyisobenzofuran-5-yl) -ethylidene] - cyclopent-1-yl}acetate. IOC. Preparation of 2. varying R 7 Similarly, following the procedures of Example 10A above, but replacing methyl (E) -6- (1,3-dihydro-4-hydroxy-6-ethyl-7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate with other compoundε of Formula A where Z iε a εidechain of Formula ZA, in which G iε lower alkoxy, the following exemplary intermediateε of Formula 2 are prepared: methyl (E) 6- (l,3-dihydro-7-methyl-3-oxo-4-trifluoromethyl- εulfonyloxy-6-vinylisobenzofuran-5-yl) -4-methyl-4-hexenoate,- methyl (E) 6- (l,3-dihydro-6,7-dimethyl-3-oxo-4-trifluoromethyl- sulfonyloxyisobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) 6- (l,3-dihydro-6-ethyl-7-methyl-3-oxo-4- trifluoromethylεulfonyloxyiεobenzofuran-5-yl) -4-methyl-4- hexenoate; methyl (E) 6- (6-cyclopropyl-1,3-dihydro-7-methyl-3-oxo-4- trifluoromethylsulfonyloxyisobenzofuran-5-yl) -4-methyl-4- hexenoate; methyl (E) 6- (l,3-dihydro-6-fluorovinyl-7-methyl-3-oxo-4- trifluoromethylεulfonyloxyiεobenzofuran-5-yl) -4-methyl-4- hexenoate; methyl (E) 6- (l,3-dihydro-7-methyl-3-oxo-4-trifluoromethyl- εulfonyloxy-6-trifluorovinylisobenzofuran-5-yl) -4-methyl-4- hexenoate; methyl (E) 6- (l,3-dihydro-7-methyl-3-oxo-6- (prop-2-enyl) -4- trifluoromethylεulfonyloxyiεobenzofuran-5-yl) -4-methyl-4- hexenoate; methyl (E) 6- (l,3-dihydro-6-ethynyl-7-methyl-3-oxo-4- trifluoromethylεulfonyloxyiεobenzofuran-5-yl) -4-methyl-4- hexenoate; methyl (E) 6- (1,3-dihydro-7-methyl-3-oxo-6- (pent-2-ynyl) -4- trifluoromethylsulfonyloxyisobenzofuran-5-yl) -4-methyl-4- hexenoate; methyl (E) 6- (6-allyl-l,3-dihydro-7-methyl-3-oxo-4- trifluoromethylεulfonyloxyiεobenzofuran-5-yl) -4-methyl-4- hexenoate; and methyl (E) 6- (1,3-dihydro-6-methoxybenzyloxymethyl-7-methyl-3-oxo-4- •• trifluoromethylsulfonyloxyiεobenzofuran-5-yl) -4-methyl-4- hexenoate. 10D. Preparation of . varying R 7 and Z Similarly, following the procedureε of Example 10A above, but replacing methyl (E) -6- (1,3-dihydro-4-hydroxy-6-ethyl-7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate with other compoundε of Formula A where Z iε a εidechain of Formula ZA, ZB, ZC, ZD, ZE, ZF. ZG, or ZH, in which G iε lower alkoxy, other intermediateε of Formula 2 correεponding to thoεe liεted in the tableε in Example IB are prepared. EXAMPLE 11 Preparation of Compounds of Formula 3 11A. Preparation of 3 where Z is ZA. in which Z' is Methyl, Z 2 . Z 3 . and Z 4 are Hydrogen. R 7 is Ethyl, and G is Methoxy A nitrogen-fluεhed mixture of 5.8 g (12.4 mmol) of methyl (E)-6-(l,3- dihydro-6-ethyl-7-methyl-4-trifluoromethyl-εulfonyloxy-3-oxoiεobenzofuran- 5-yl) -4-methyl- -hexenoate, 1.5 g of potaεεium cyanide, and 1.11 g of tetrakiε(triphenylphoεphine) palladium in 100 ml of 1,4-dioxane is heated at reflux for 18 hours. Upon cooling, the mixture iε partitioned between water and ethyl acetate. The organic phase iε washed with water six ti eε, with brine once, and then dried over magneεium εulfate. The εolvent iε evaporated under reduced preεεure and the residue purified by εilica gel chromatography, to give methyl (E) -6- (4-cyano-l,3-dihydro-6-ethyl-7-methyl- 3-oxoisobenzofuran-5-yl) -4-methyl-4-hexenoate. 11B. Preparation of 3. varying Z Similarly, following the procedures of Example 11A above, but replacing methyl (E) -6- (l,3-dihydro-6-ethyl-7-methyl-3-oxo-4- trifluoromethylsulfonyloxyisobenzofuran-5-yl) -4-methyl-4-hexenoate with other compounds of Formula 2, the following intermediateε of Formula 3 are prepared: methyl (E) -6- (4-cyano-l,3-dihydro-6-ethyl-7-methyl-3- oxoiεobenzofuran-5-yl) -3,4-dimethyl-4-hexenoate; and methyl (E)-2-{2-[2- (4-cyano-1,3-dihydro-6-ethyl-7-methyl-3- oxoiεobenzofuran-5-yl) -ethylidene] -cyclopent-1-yl}acetate. 11C. Preparation of 3. varying R 7 Similarly, following the procedureε of Example 11A above, but replacing methyl (E) -6- (l,3-dihydro-6-ethyl-7-methyl-3-oxo-4- trifluoromethylεulfonyloxyiεobenzofuran-5-yl) - -methyl-4-hexenoate with other compoundε of Formula 2 where Z iε a sidechain of Formula ZA, in which G iε lower alkoxy, the following exemplary intermediateε of Formula 3 are prepared: methyl (E) 6- (4-cyano-l,3-dihydro-7-methyl-3-oxo-6- vinylisobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) 6- (4-cyano-1,3-dihydro-6,7-dimethyl-3-oxoisobenzofuran-5- yl) -4-methyl-4-hexenoate; methyl (E) 6- (4-cyano-l,3-dihydro-6-ethyl-7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) 6- (4-cyano-6-cyclopropyl-1,3-dihydro-7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) 6- (4-cyano-l,3-dihydro-6-fluorovinyl-7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) 6- (4-cyano-l,3-dihydro-7-methyl-3-oxo-6- trifluorovinyliεobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) 6- (4-cyano-l,3-dihydro-7-methyl-3-oxo-6- (prop-2- enyl)iεobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) 6- (4-cyano-1,3-dihydro-6-ethynyl-7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) 6- (4-cyano-l,3-dihydro-7-methyl-3-oxo-6- (pent-2- ynyl) iεobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) 6- (6-allyl-4-cyano-l,3-dihydro-7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate; and methyl (E) 6- (4-cyano-l,3-dihydro-6- (4-methoxybenzyloxy-methyl) -7- methyl-3-oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate. 11D. Preparation of 3. varying R 7 and Z Similarly, following the procedures of Example 11A above, but replacing methyl (E) -6- (1,3-dihydro-6-ethyl-7-methyl-4- trifluoromethylεulfonyloxy-3-oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate with other compoundε of Formula 2 where Z iε a εidechain of Formula ZA, ZB, ZC, ZD, ZE, ZF. ZG, or ZH, in which G iε lower alkoxy, other intermediates of Formula 3 corresponding to those listed in the tableε in Example IB are prepared. EXAMPLE 12 Preparation of Compoundε of Formula 4 12A. Preparation of 4 where Z iε ZA. in which Z' iε Methyl. Z 2 . Z 3 . and Z 4 are Hydrogen. R 7 iε Ethyl. and G is Methoxy A mixture of 4.0 g of methyl (E) -6- (4-cyano-l,3-dihydro-6-ethyl-7- methyl-3-oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate and 1.86 g of sodium hydroxide in 100 ml of 3:2 water:methanol iε heated at reflux for 2 hourε. The reεulting homogenouε εolution iε diεtilled until 30 ml of diεtillate iε recovered. An additional 0.6 g (15 mmol) of εodium hydroxide iε added to the reaction εolution and it iε refluxed for 2 dayε. Upon cooling the εolution is partitioned between IN aqueous HCl and ethyl acetate. The organic phase iε waεhed twice with water, once with brine, and then dried over magneεium εulfate. The εolvent iε evaporated under reduced preεεure to give (E) -6- (4-carboxy-l,3-dihydro-6-ethyl-7-methyl-3-oxoiεobenzofuran-5- yl) -4-methyl-4-hexenoic acid. 12B. Preparation of 4. varying R 7 and Z Similarly, following the procedures of Example 12A above, but replacing methyl (E) -6- (4-cyano-l,3-dihydro-6-ethyl-7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate with other compounds of Formula 3, the following intermediates of Formula 4 are prepared: (E) -6- (4-carboxy-l,3-dihydro-6-ethyl-7-methyl-3-oxoiεobenzofuran-5- yl) -3,4-dimethyl-4-hexenoic acid; and (E) -2-{2- [2- (4-carboxy-1,3-dihydro-6-ethyl-7-methyl-3- oxoiεobenzofuran-5-yl) -ethylidene] -cyclopent-1-yl}acetic acid. 12C. Preparation of 4. varying R 7 Similarly, following the procedureε of Example 12A above, but replacing methyl (E) -6- (4-cyano-l,3-dihydro-6-ethyl-7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate with other compounds of Formula 3 where Z iε a εidechain of Formula ZA, in which G iε lower alkoxy, the following exemplary intermediateε of Formula 4 are prepared: (E) 6- (4-carboxy-l,3-dihydro-7-methyl-3-oxo-6-vinyliεobenzofuran-5- yl) -4-methyl-4-hexenoic acid; (E) 6- (4-carboxy-l,3-dihydro-6,7-dimethyl-3-oxoiεobenzofuran-5-yl) -4- methyl-4-hexenoic acid; (E) 6- (4-carboxy-1,3-dihydro-6-ethyl-7-methyl-3-oxoiεobenzofuran-5- yl) -4-methyl-4-hexenoic acid; (E) 6- (4-carboxy-6-cyclopropyl-l,3-dihydro-7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoic acid; (E) 6- (4-carboxy-l,3-dihydro-6-fluorovinyl-7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoic acid; (E) 6- (4-carboxy-l,3-dihydro-7-methyl-3-oxo-6- trifluorovinyliεobenzofuran-5-yl) -4-methyl-4-hexenoic acid; (E) 6- (4-carboxy-1,3-dihydro-7-methyl-3-oxo-6- (prop-2- enyl)iεobenzofuran-5-yl) -4-methyl-4-hexenoic acid; (E) 6- (4-carboxy-l,3-dihydro-6-ethynyl-7-methyl-3-oxoiεobenzofuran-5- yl) -4-methyl-4-hexenoic acid; (E) 6- (4-carboxy-1,3-dihydro-7-methyl-3-oxo-6- (pent-2- ynyl)isobenzofuran-5-yl) -4-methyl-4-hexenoic acid; (E) 6- (6-allyl-4-carboxy-1,3-dihydro-7-methyl-3-oxoisobenzofuran-5- yl) -4-methyl-4-hexenoic acid; and (E) 6- (4-carboxy-1,3-dihydro-6- (4-methoxybenzyloxymethyl) -7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoic acid. 12D. Preparation of , varying R 7 and Z Similarly, following the procedureε of Example 12A above, but replacing methyl (E) -6- (4-cyano-l,3-dihydro-6-ethyl-7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate with other compoundε of Formula 3 where Z is a sidechain of Formula ZA, ZB, ZC, ZD, ZE, ZF. ZG, or ZH, in which G is lower alkoxy, other intermediateε of Formula 4 correεponding to thoεe liεted in the tableε in Example IB are prepared. EXAMPLE 13 Preparation of Compounds of Formula 5 13A. Preparation of 5 where Z is ZA. in which Z 1 is Methyl. Z 2 . Z 3 . and Z 4 are Hydrogen, and R 7 is Ethyl and G is Methoxy A solution of 3.88 g of (E) -6- (4-carboxy-l,3-dihydro-6-ethyl-7- methyl-3-oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoic acid and 0.2 g of p-tolueneεulfonic acid in methanol (60 ml) iε εtirred at room temperature for 8 hourε. The εolvent iε evaporated under reduced preεεure. The residue is disεolved in ethyl acetate, and thiε εolution waεhed twice with water, once with brine, and dried over magneεium εulfate. The εolvent iε evaporated under reduced pressure to give methyl (E) -6- (4-carboxy-1,3- dihydro-6-ethyl-7-methyl-3-oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate. 13B. Preparation of 5, varying R 7 and Z Similarly, following the procedureε of Example 13A above, but replacing (E) -6- (4-carboxy-l,3-dihydro-6-ethyl-7-methyl-3-oxoiεobenzofuran- 5-yl) -4-methyl-4-hexenoic acid with other compoundε of Formula 4, the following intermediateε of Formula 5 are prepared: methyl (E) -6- (4-carboxy-l,3-dihydro-6-ethyl-7-methyl-3-oxo- iεobenzofuran-5-yl) -3,4-dimethyl-4-hexenoate; and methyl (E) -2-{2- [2- (4-carboxy-l,3-dihydro-6-ethyl-7-methyl-3- oxoiεobenzofuran-5-yl) -ethylidene] -cyclopent-1-yl}acetate. 13C. Preparation of 5. varying R 7 Similarly, following the procedureε of Example 13A above, but replacing (E) -6- (4-carboxy-l,3-dihydro-6-ethyl-7-methyl-3-oxoiεobenzofuran- 5-yl) -4-methyl- -hexenoic acid with other compoundε of Formula 4 where Z iε a sidechain of Formula ZA, in which G is lower alkoxy, the following exemplary intermediates of Formula 5 are prepared: methyl (E) 6- (4-carboxy-l,3-dihydro-7-methyl-3-oxo-6- vinyliεobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) 6- (4-carboxy-l,3-dihydro-6,7-dimethyl-3-oxoiεobenzofuran- 5-yl) -4-methyl-4-hexenoate; methyl (E) 6- (4-carboxy-l,3-dihydro-6-ethyl-7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) 6- (4-carboxy-6-cyclopropyl-1,3-dihydro-7-methyl-3- oxoisobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) 6- (4-carboxy-1,3-dihydro-6-fluorovinyl-7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) 6- (4-carboxy-1,3-dihydro-7-methyl-3-oxo-6- trifluorovinyliεobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) 6- (4-carboxy-l,3-dihydro-7-methyl-3-oxo-6- (prop-2- enyl)iεobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) 6- (4-carboxy-1,3-dihydro-6-ethynyl-7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) 6- (4-carboxy-l,3-dihydro-7-methyl-3-oxo-6- (pent-2- ynyl)iεobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) 6- (6-allyl-4-carboxy-1,3-dihydro-7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate; and methyl (E) 6- (4-carboxy-1,3-dihydro-6- (4-methoxybenzyloxy-methyl) -7- . • methyl-3-oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate. 13D. Preparation of 5. varying R 7 and Z Similarly, following the procedureε of Example 13A above, but replacing (E) -6- (4-carboxy-l,3-dihydro-6-ethyl-7-methyl-3-oxoiεobenzofuran- 5-yl) -4-methyl-4-hexenoic acid with other compoundε of Formula 4 where Z iε a εidechain of Formula ZA, ZB, ZC, ZD, ZE, ZF. ZG, or ZH, in which G iε lower alkoxy, other intermediateε of Formula 5 correεponding to those listed in the tableε in Example IB are prepared. EXAMPLE 14 Preparation of Compounds of Formula 6 14A. Preparation of 6 where Z is ZA, in which Z' is Methyl. Z 2 . Z 3 . and Z 4 are Hydrogen, and R 7 is Ethyl and G is Methoxy To a stirred, 0°C εolution of 6.0 g of methyl (E) -6- (4-carboxy-1,3- dihydro-6-ethyl-7-methyl-3-oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate in 150 ml of dimethylformamide iε added 4.62 ml of triethylamine followed by dropwiεe addition of 4.5 ml of diphenylchlorophoεphate. The mixture is allowed to stir at room temperature for 1 hour and then recooled to 0°C, and treated with 10.8 g of sodium azide. This mixture is stirred for 24 hours at 0°C and then partitioned between aqueous εodium hydrogen εulfate and ethyl acetate. The organic phase is waεhed four times with water, dried over magnesium sulfate, and concentrated under reduced pressure to give methyl (E) -6- (l,3-dihydro-6-ethyl-4-isocyanato-7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate. 14B. Preparation of 6. varying R 7 and Z Similarly, following the procedureε of Example 14A above, but replacing methyl (E) -6- (4-carboxy-l,3-dihydro-6-ethyl-7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate with other compoundε of Formula 5, the following intermediateε of Formula 6 are prepared: methyl (E) -6- (l,3-dihydro-6-ethyl-4-isocyanato-7-methyl-3-oxo- iεobenzofuran-5-yl) -3,4-dimethyl-4-hexenoate; and methyl (E) -2-{2- [2- (l,3-dihydro-6-ethyi-4-isocyanato-7-methyl-3- oxoiεobenzofuran-5-yl) -ethylidene] -cyclopent-1-yl}acetate. 14C. Preparation of 6. varying R 7 Similarly, following the procedureε of Example 14A above, but replacing methyl (E) -6- (4-carboxy-l,3-dihydro-6-ethyl-7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate with other compoundε of Formula 5 where Z is a εidechain of Formula ZA, in which G iε lower alkoxy, the following exemplary intermediateε of Formula 6 are prepared: methyl (E) 6- (l,3-dihydro-4-isocyanato-7-methyl-3-oxo-6- vinyliεobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) 6- (1,3-dihydro-6,7-dimethyl-4-isocyanato-3- oxoisobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) 6- (l,3-dihydro-6-ethyl-4-iεocyanato-7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) 6- (6-cyclopropyl-l,3-dihydro-4-isocyanato-7-methyl-3- oxoisobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) 6- (1,3-dihydro-6-fluorovinyl-4-iεocyanato-7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) 6- (1,3-dihydro-4-iεocyanato-7-methyl-3-oxo-6- trifluorovinyliεobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) 6- (l,3-dihydro-4-iεocyanato-7-methyl-3-oxo-6- (prop-2- enyl)iεobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) 6- (1,3-dihydro-6-ethynyl-4-isocyanato-7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) 6- (l,3-dihydro-4-isocyanato-7-methyl-3-oxo-6- (pent-2- ynyl)iεobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) 6- (6-allyl-l,3-dihydro-4-iεocyanato-7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate; and methyl (E) 6- (1,3-dihydro-4-iεocyanato-6- (4-methoxybenzyloxymethyl) - 7-methyl-3-oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate. 14D. Preparation of 6. varying R 7 and Z Similarly, following the procedureε of Example 14A above, but replacing (E) -6- (4-carboxy-l,3-dihydro-6-ethyl-7-methyl-3-oxoiεobenzofuran- 5-yl) -4-methyl-4-hexenoic acid with other compoundε of Formula 5 where Z iε a εidechain of Formula ZA, ZB, ZC, ZD, ZE, ZF. ZG, or ZH, in which G iε lower alkoxy, other intermediateε of Formula 6 corresponding to those listed in the tableε in Example IB are prepared. EXAMPLE 15 Preparation of Compoundε of Formula I ISA. Formula IA where Z iε ZA. in which Z' iε Methyl. Z 2 . Z 3 . and Z 4 are Hydrogen, and R 7 is Ethyl and G is Hvdroxy 2.0 g of methyl (E) -6- (l,3-dihydro-6-ethyl-4-isocy__nato-7-methyl-3- oxoisobenzofuran-5-yl) -4-methyl-4-hexenoate iε diεεolved in 50 ml of 1,4-dioxane and treated with 16 ml of water and 2.0 g of lithium hydroxide monohydrate. The mixture iε stirred at room temperature for 2 hours and then partitioned between aqueouε IN sodium hydrogen sulfate and ethyl acetate. The organic phase is waεhed twice with water, once with brine, and dried over magneεium εulfate. The εolvent iε evaporated under reduced preεεure auid the reεidue purified by chromatography on εilica gel, to give (E) -6- (4-amino-l,3-dihydro-6-ethyl-7-methyl-3-oxoiεobenzofuran-5-yl) -4- methyl-4-hexenoic acid. 15B. Preparation of IA, varying R 7 and Z Similarly, following the procedureε of Example 15A above, but replacing methyl (E) -6- (l,3-dihydro-6-ethyl-4-isocyanato-7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate with other compounds of Formula 6, the following intermediates of Formula IA are prepared: (E) -6- (4-amino-l,3-dihydro-6-ethyl-7-methyl-3-oxoisobenzofuran-5-yl) - 3,4-dimethyl-4-hexenoic acid; and (E) -2-{2- [2- (4-amino-l,3-dihydro-6-ethyl-7-methyl-3-oxoiεobenzofuran- 5-yl) -ethylidene] -cyclopent-l-yl}acetic acid. 15C. Preparation of IA, varying R 7 Similarly, following the procedures of Example 14A above, but replacing methyl (E) -6- (l,3-dihydro-6-ethyl-4-iεocyanato-7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate with other compoundε of Formula 6 where Z is a εidechain of Formula ZA, in which G iε lower alkoxy, the following exemplary intermediateε of Formula 6 are prepared: (E) 6- (4-amino-l,3-dihydro-7-methyl-3-oxo-6-vinyliεobenzofuran-5-yl) - 4-methyl-4-hexenoate; (E) 6- (4-amino-l,3-dihydro-6,7-dimethyl-3-oxoiεobenzofuran-5-yl) -4- methyl-4-hexenoate; (E) 6- (4-amino-l,3-dihydro-6-ethyl-7-methyl-3-oxoiεobenzofuran-5-yl) - 4-methyl-4-hexenoate; (E) 6- (4-amino-6-cyclopropyl-1,3-dihydro-7-methyl-3-oxoiεobenzofuran- 5-yl) -4-methyl-4-hexenoate; (E) 6- (4-amino-l,3-dihydro-6-fluorovinyl-7-methyl-3-oxoiεobenzofuran- 5-yl) -4-methyl-4-hexenoate; (E) 6- (4-amino-l,3-dihydro-7-methyl-3-oxo-6- trifluorovinyliεobenzofuran-5-yl) -4-methyl-4-hexenoate; (E) 6- (4-amino-l,3-dihydro-7-methyl-3-oxo-6- (prop-2- enyl)isobenzofuran-5-yl) -4-methyl-4-hexenoate; (E) 6- (4-amino-1,3-dihydro-6-ethynyl-7-methyl-3-oxoisobenzofuran-5- yl) -4-methyl-4-hexenoate; (E) 6- (4-amino-l,3-dihydro-7-methyl-3-oxo-6- (pent-2- ynyl)isobenzofuran-5-yl) -4-methyl-4-hexenoate; (E) 6- (6-allyl-4-amino-l,3-dihydro-7-methyl-3-oxoiεobenzofuran-5-yl) - 4-methyl-4-hexenoate; and (E) 6- (4-amino-l,3-dihydro-6- (4-methoxybenzyloxymethyl) - -methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate. 15D. Preparation of IA. varying R 7 and Z Similarly, following the procedures of Example 15A above, but replacing methyl (E) -6- (l,3-dihydro-6-ethyl-4-isocyanato-7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate with other compoundε of Formula 6 where Z iε a sidechain of Formula ZA, ZB, ZC, ZD, ZE, ZF. ZG, or ZH, in which G is lower alkoxy, the following compoundε of Formula IA where G iε hydroxy and R 7 iε ethyl are prepared: Formula IA where Z is Sidechain ZA Formula IA where Z is Sidechain ZB Formula IA where Z is Sidechain ZE H Formula IA where Z is Sidechain ZH EXAMPLE 16 Preparation of Coπtpoundε of Formula I 16A. Formula IA where Z is ZA, in which Z' is Methyl, Z 2 . Z 3 . and Z 4 are Hydrogen. R 7 is Ethyl. and G is Methoxy To a εolution of 2.5 g of (E) -6- (4-amino-l,3-dihydro-6-ethyl-7- methyl-3-oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoic acid in 50 ml (1.234 mol) of methanol iε added 0.125 g of p-tolueneεulfonic acid monohydrate. The εolution iε εtirred at room temperature for 2 days and then concentrated to a small volume, and the residue partitioned between water and ethyl acetate. The organic layer is dried over magnesium sulfate and concentrated to give methyl (E) -6- (4-amino-l,3-dihydro-6-ethyl-7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate. 16B. Preparation of IA. varying Z in which G iε Lower Alkoxy Similarly, following the procedures of Example 16A above, but optionally replacing (E) -6- (4-amino-1,3-dihydro-6-ethyl-7-methyl-3- oxoisobenzofuran-5-yl) -4-methyl-4-hexenoic acid with other compounds of Formula IA where Z is a sidechain of Formula ZA, ZB, ZC, ZD, ZE, ZF. ZG, or ZH, in which G iε hydroxy, and optionally replacing methanol with other alkanolε of formula GH, where G is lower alkoxy, the compounds of Formula IA corresponding to those liεted in the tableε in Example 15D where G iε lower alkoxy are prepared. EXAMPLE 17 Preparation of Compounds of Formula I 17A. Formula IA where Z iε ZA. in which z' is Methyl. z 2 , Z 3 . and Z 4 are Hydrogen. R 7 is Ethyl. and G is Morpholinoethoxy 7g of (E) -6- (4-amino-l,3-dihydro-6-ethyl-7-methyl-3-oxoisobenzofuran- 5-yl) -4-methyl-4-hexenoic acid and toluene (25ml) are warmed gently to form a εolution. A slight excesε of 2-morpholinoethanol (3g) and toluene (25ml) are added. The reaction mixture is stirred for half an hour and then heated to reflux at an initial pot temperature of 117°C (which increases a few degrees during reflux) under a Dean-Stark trap for 80 hourε. The reaction mixture iε cooled, waεhed with water (2 X 15ml) , 10% aqueouε εodium bicarbonate (2 x 15ml) and finally with water (15ml) . The toluene layer iε εtripped to a volume of about 20ml in vacuo. n-hexane (30ml) iε added and the reεulting εlurry iε aged at room temperature for 2 hourε. The product iε filtered, washed with n-hexane (ca. 10 ml) and dried in vacuo at 60°C to yield 2- (morpholin-4-yl)ethyl (E) -6- (4-amino-1,3-dihydro- 6-ethyl-7-methyl-3-oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate. 17B. Preparation of IA. varying Z in which G is Morpholinoethoxy Similarly, following the procedureε of Example 17A above, but replacing (E) -6- (4-amino-1,3-dihydro-6-ethyl-7-methyl-3-oxoisobenzofuran-5- yl) -4-methyl-4-hexenoic acid with other compoundε of Formula IA where Z is a sidechain of Formula ZA, ZB, ZC, ZD, ZE, ZF. ZG, or ZH, in which G iε hydroxy, the correεponding compoundε of Formula IA where G iε morpholinoethoxy are prepared. EXAMPLE 18 Preparation of Compounds of Formula I 18A. Formula IB where R 4 and R 5 are Methyl, R 7 is Ethyl. and Z is ZA. in which Z' is Methyl, Z 2 . Z 3 . and Z 4 are Hydrogen, and G iε Methoxy A εolution of 0.65 g (1.8 mmol) of methyl (E) -6- (l,3-dihydro-4- iεocyanato-6-ethyl-7-methyl-3-oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate in 10 ml of tetrahydrofuran is treated with 5 ml of a solution of 40% dimethylamine in water. After 1 hour the reaction iε partitioned between water and ethyl acetate. The organic phaεe iε washed with water three timeε, dried over magnesium sulfate, and concentrated under reduced pressure to give methyl (E) -6- [l,3-dihydro-4- (3,3-dimethylureido) -6-ethyl- 7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate. 18B. Preparation of IB. varying Z Similarly, following the procedures of Example 18A above, but replacing methyl (E) -6- (l,3-dihydro-4-isocyanato-6-ethyl-7-methyl-3- oxoisobenzofuran-5-yl) -4-methyl-4-hexenoate with other compounds of Formula 6 where Z iε a εidechain of Formula ZA, ZB, ZC, ZD, ZE, ZF. ZG, or ZH, in which G iε lower alkoxy, the corresponding compoundε of Formula IB where G is lower alkoxy are prepared. EXAMPLE 19 Preparation of Compounds of Formula I 19A. Formula IB where R 4 and R 5 are Methyl, R 7 is Ethyl, and Z is ZA. in which Z' is Methyl. Z 2 . Z 3 . and Z 4 are Hydrogen, and G is Hvdroxy To a εolution of 0.3 g (0.74 mmol) of methyl (E) -6- [1,3-dihydro-4- (3,3-dimethylureido) -6-ethyl-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4- hexenoate in 7.4 ml of 4:1 methanol:water iε added 0.13 g (2.96 mmol) of lithium hydroxide monohydrate. The εolution iε heated at 50-60°C for 4 hourε. Upon cooling, the reaction iε partitioned between aqueouε εodium hydrogen εulfate and ethyl acetate. The organic layer iε washed with brine, dried over magnesium sulfate, and concentrated to give (E)-6-[l,3- dihydro-4- (3,3-dimethylureido) -6-ethyl-7-methyl-3-oxoiεobenzofuran-5-yl] -4- methyl-4-hexenoic acid. 19B. Preparation of IB. varying R 4 . R 5 . R 7 , and Z in which G is Hvdroxy Similarly, following the procedureε of Example 19A above, but replacing methyl (E) -6- [l,3-dihydro-4- (3,3-dimethylureido) -6-ethyl-7- methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate with other compoundε of Formula IB in which G iε lower alkoxy, the following exemplary intermediates of Formula IB where G iε hydroxy are prepared: (E) -6- (l,3-dihydro-4- (3,3-dimethylureido) -6-ethyl-7-methyl-3-oxo¬ iεobenzofuran-5-yl) -3,4-dimethyl-4-hexenoic acid; (E) -2-{2- [2- (1,3-dihydro-4- (3,3-dimethylureido) -6-ethyl-7-methyl-3- oxoiεobenzofuran-5-yl) -ethylidene] -cyclopent-l-yl}acetic acid; (E) 6- (l,3-dihydro-4- (3,3-dimethylureido) -7-methyl-3-oxo-6- vinyliεobenzofuran-5-yl) -4-methyl-4-hexenoate; (E) 6- (1,3-dihydro-6,7-dimethyl-4- (3,3-dimethylureido) -3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate; (E) 6- (l,3-dihydro-4- (3,3-dimethylureido) -6-ethyl-7-methyl-3- oxoisobenzofuran-5-yl) -4-methyl-4-hexenoate; (E) 6- (e-cyclopropy 1 - 1 ' 3 -^^^ 0 - 4 - ( 3,3-dimethylureido) -7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate; (E) 6- (l,3-dihydro-4- (3,3-dimethylureido) -6-fluorovinyl-7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate; (E) 6- (l,3-dihydro-4- (3,3-dimethylureido) -7-methyl-3-oxo-6- trifluorovinylisobenzofuran-5-yl) -4-methyl-4-hexenoate; (E) 6- (1,3-dihydro-4- (3,3-dimethylureido) -7-methyl-3-oxo-6- (prop-2- enyl)iεobenzofuran-5-yl) -4-methyl-4-hexenoate; (E) 6- (l,3-dihydro-4- (3,3-dimethylureido) -6-ethynyl-7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate; (E) 6- (l,3-dihydro-4- (3,3-dimethylureido) -7-methyl-3-oxo-6- (pent-2- ynyl)iεobenzofuran-5-yl) -4-methyl-4-hexenoate; (E) 6- (6-allyl-l,3-dihydro-4- (3,3-dimethylureido) -7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate; and (E) 6- (l,3-dihydro-4- (3,3-dimethylureido) -6- (4- methoxybenzyloxymethyl) -7-methyl-3-oxoiεobenzofuran-5-yl) -4- methyl-4-hexenoate. 19C. Preparation of IB. varying Z Similarly, following the procedureε of Example 18A and 19A above, but replacing methyl (E) -6- [l,3-dihydro-4- (3,3-dimethylureido) -6-ethyl-7- ethyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate with other compounds of Formula IB where Z iε a sidechain of Formula ZA, ZB, ZC, ZD, ZE, ZF. ZG, or ZH, in which G is lower alkoxy, the following compoundε of Formula IB where G iε hydroxy and R 7 is ethyl are prepared: EXAMPLE 20 Preparation of Compoundε of Formula I Formula IC where R 3 is -CF.. and Z is ZA. in which Z' iε Methyl. Z 2 . SUBSTITUTE SHEET (RULE 2β) Z 3 , and Z 4 are Hydrogen, and R 7 iε Ethyl and G is Methoxy To a solution of 0.5 g of methyl (E) -6- (4-amino-1,3-dihydro-6-ethyl- 7-methyl-3-oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate in 5 ml of dichloromethane is added 0.5 ml of trifluoroacetic anhydride. After 1 hour the reaction is partitioned between water and dichloromethane. The organic layer is washed twice with water, dried over magnesium sulfate, and concentrated to give methyl (E) -6- [l,3-dihydro-6-ethyl-7-methyl-3-oxo-4- trifluoroacetylaminoiεobenzofuran-5-yl] -4-methyl-4-hexenoate. 20B. Formula IC where R 3 is -CF.. varying R 7 and Z Similarly, following the procedures of Example 20A above, but replacing methyl (E) -6- (4-amino-l,3-dihydro-6-ethyl-7-methyl-3- oxoisobenzofuran-5-yl) -4-methyl-4-hexenoate with other compoundε of Formula IA in which G iε lower alkoxy, the following exemplary intermediateε of Formula IC where G iε lower alkoxy are prepared: methyl (E) -6- (1,3-dihydro-6-ethyl-7-methyl-3-oxo-4- trifluoroacetylaminoisobenzofuran-5-yl) -3,4-dimethyl-4-hexenoic acid; methyl (E) -2-{2- [2- (l,3-dihydro-6-ethyl-7-methyl-3-oxo-4- trifluoroacetylaminoiεobenzofuran-5-yl) -ethylidene] -cyclopent- l-yl}acetic acid; methyl ( E ) 6- ( l,3-dihydro-7-methyl-3-oxo-4-trifluoroacetylamino-6- vinyliεobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) 6- (l,3-dihydro-6,7-dimethyl-3-oxo-4- trifluoroacetylaminoiεobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) 6- (1,3-dihydro-6-ethyl-7-methyl-3-oxo-4- trifluoroacetylaminoiεobenzofuran-5-yl) -4-methyl-4-hexenoate,• methyl (E) 6- (6-cyclopropyl-l,3-dihydro-7-methyl-3-oxo-4- trifluoroacetylaminoiεobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) 6- (l,3-dihydro-6-fluorovinyl-7-methyl-3-oxo-4- trifluoroacetylaminoiεobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl ( E ) 6- ( l,3-dihydro-7-methyl-3-oxo-4-trifluoroacetylamino-6- trifluorovinyliεobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) 6- (l,3-dihydro-7-methyl-3-oxo-6- (prop-2-enyl) -4- trifluoroacetylaminoiεobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) 6- (l,3-dihydro-6-ethynyl-7-methyl-3-oxo-4- trifluoroacetylaminoiεobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) 6- (1,3-dihydro-7-methyl-3-oxo-6- (pent-2-ynyl) -4- trifluoroacetylaminoiεobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) 6- (6-allyl-l,3-dihydro-7-methyl-3-oxo-4- trifluoroacetylaminoiεobenzofuran-5-yl) -4-methyl-4-hexenoate; and methyl (E) 6- ( 1,3-dihydro-6-methoxybenzyloxymethyl-7-methyl-3-oxo-4- trifluoroacetylaminoiεobenzofuran-5-yl) -4-methyl-4-hexenoate. 20C. Preparation of IC. varying Z Similarly, following the procedureε of Example 20A above, but replacing methyl (E) -6- (4-amino-l,3-dihydro-6-ethyl-7-methyl-3- oxoisobenzofuran-5-yl) -4-methyl-4-hexenoate with other compounds of Formula IA where Z is a sidechain of Formula ZA, ZB, ZC, ZD, ZE, ZF. ZG, or ZH, in which G is lower alkoxy, and optionally replacing trifluoroacetic anhydride with other compounds of the formula (R 3 C(0)) 2 0 or of the formula R 3 C(0)C1, where R 3 is as defined in the Summary of the Invention, the following compounds of Formula IC where G iε hydroxy and R 7 iε ethyl are prepared: -129- Formula IC where Z is Sidechain ZE -131 - Formula IC where Z is Sidechain ZH EXAMPLE 21 Preparation of Compounds of Formula I 21A. Formula ID where R' is Methyl. R 3 is -CF,. R 7 is Ethyl. and Z is ZA. in which Z' is Methyl. Z 2 . Z 3 . and Z 4 are Hydrogen, and G is Methoxy To a solution of 0.35 g of methyl (E) -6- [l,3-dihycLro-6-ethyl-7- methyl-4-trifluoroacetylamino-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate in 4 ml of dimethylformamide is added 0.47 g of potassium carbonate and 0.23 ml of iodomethane. The mixture is stirred for 24 hours and then partitioned between ethyl acetate and water. The organic layer is washed with water, dried over magnesium sulfate, and concentrated under reduced presεure to give methyl (E) -6- [l,3-dihydro-6-ethyl-7-methyl-4- (N-trifluoroacetyl-N-methyl)amino-3-oxoiεobenzofuran-5-yl] -4-methyl-4- hexenoate. 21B. Formula ID where R 3 is -CF,. varying R 7 and Z Similarly, following the procedures of Example 21A above, but replacing methyl (E) -6- [l,3-dihydro-6-ethyl-7-methyl-4- trifluoroacetylamino-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate with other compounds of Formula IC in which G is lower alkoxy, the following exemplary intermediates of Formula ID where G is lower alkoxy are prepared: methyl (E) -6- (l,3-dihydro-6-ethyl-7-methyl-3-oxo-4- (N- syesimπi Hir ROLE 26 trifluoroacetyl-N-methyl)aminoiεobenzofuran-5-yl) -3,4-dimethyl- 4-hexenoic acid; methyl (E) -2-{2- [2- (l,3-dihydro-6-ethyl-7-methyl-4- (N- trifluoroacetyl-N-methyl)amino-3-oxoiεobenzofuran-5-yl) - ethylidene] -cyclopent-l-yl}acetic acid; methyl (E) 6- (l,3-dihydro-7-methyl-3-oxo-4- (N-trifluoroacetyl-N- methyl)amino-6-vinyliεobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) 6- (l,3-dihydro-6,7-dimethyl-3-oxo-4- (N-trifluoroacetyl-N- methyl)aminoiεobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) 6- (1,3-dihydro-6-ethyl-7-methyl-3-oxo-4- (N- trifluoroacetyl-N-methyl)aminoiεobenzofuran-5-yl) -4-methyl-4- hexenoate; methyl (E) 6- (6-cyclopropyl-1,3-dihydro-7-methyl-3-oxo-4- (N- trifluoroacetyl-N-methyl)aminoiεobenzofuran-5-yl) -4-methyl-4- hexenoate; methyl (E) 6- (1,3-dihydro-6-fluorovinyl-7-methyl-3-oxo-4- (N- trifluoroacetyl-N-methyl)aminoisobenzofuran-5-yl) -4-methyl-4- hexenoate; methyl (E) 6- (1,3-dihydro-7-methyl-3-oxo-4- (N-trifluoroacetyl-N- methyl)amino-6-trifluorovinyliεobenzofuran-5-yl) -4-methyl-4- hexenoate; methyl (E) 6- (l,3-dihydro-7-methyl-3-oxo-6- (prop-2-enyl) -4- (N- trifluoroacetyl-N-methyl)aminoiεobenzofuran-5-yl) -4-methyl-4- hexenoate; methyl (E) 6- (l,3-dihydro-6-ethynyl-7-methyl-3-oxo-4- (N- trifluoroacetyl-N-methyl)aminoiεobenzofuran-5-yl) -4-methyl-4- hexenoate; methyl (E) 6- (1,3-dihydro-7-methyl-3-oxo-6- (pent-2-ynyl) -4- (N- trifluoroacetyl-N-methyl)aminoisobenzofuran-5-yl) -4-methyl-4- hexenoate; methyl (E) 6- (6-allyl-l,3-dihydro-7-methyl-3-oxo-4- (N- trifluoroacetyl-N-methyl)aminoiεobenzofuran-5-yl) -4-methyl-4- hexenoate; and methyl (E) 6- (l,3-dihydro-6- (4-methoxybenzyloxymethyl) -7-methyl-3- oxo-4- (N-trifluoroacetyl-N-methyl)aminoiεobenzofuran-5-yl) -4- methyl- -hexenoate. 21C. Preparation of ID. var y ing Z Similarly, following the procedures of Example 21A above, but replacing methyl (E) -6- [1,3-dihydro-6-ethyl-7-methyl-4- trifluoroacetylamino-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate with other compoundε of Formula IC where Z iε a εidechain of Formula ZA, ZB, ZC, ZD, ZE, ZF. ZG, or ZH, in which G iε lower alkoxy, and optionally replacing iodomethane by other lower alkyl halideε of the formula R'Br or R'l, the following compoundε of Formula ID where G iε hydroxy and R 7 iε ethyl are prepared: Formula ID where Z iε Sidechain ZB SUδSUππi SHEET (RULE 26 Formula ID where Z is Sidechain ZH SUSSTΠUTE SHEET ROLE 26 EXAMPLE 22 Preparation of Compounds of Formula I 22A. Formula IE where R' is Methyl. R 7 is Ethyl, and Z is ZA. in which Z' is Methyl. Z 2 . Z 3 , and Z 4 are Hydrogen, and G is Hydroxy Hydrolyεiε of methyl (E) -6- [l,3-dihydro-6-ethyl-7-methyl-4- (N-trifluoroacetyl-N-methyl)amino-3-oxoiεobenzofuran-5-yl] -4-methyl-4- hexenoate iε carried on the same manner as εhown in Example 19A to give methyl (E) -6- (1,3-dihydro-6-ethyl-7-methyl-4-methylamino-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate. 22B. Formula IE where R 3 is -CF,. varying R 7 and Z Similarly, following the procedures of Example 22A above, but replacing methyl (E) -6- [1,3-dihydro-6-ethyl-7-methyl-4- (N-trifluoroacetyl-N-methyl)amino-3-oxoiεobenzofuran-5-yl] -4-methyl-4- hexenoate with other compoundε of Formula ID in which G iε lower alkoxy, the following exemplary intermediateε of Formula IE where G iε lower alkoxy are prepared: methyl (E) -6- (l,3-dihydro-6-ethyl-7-methyl-4-methylamino-3- oxoiεobenzofuran-5-yl) -3,4-dimethyl-4-hexenoic acid; methyl (E) -2-{2- [2- (1,3-dihydro-6-ethyl-7-methyl-4-methylamino-3- oxoiεobenzofuran-5-yl) -ethylidene] -cyclopent-l-yl}acetic acid; methyl (E) 6- (1,3-dihydro-7-methyl-3-oxo-4-methylamino-6- vinyliεobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) 6- (1,3-dihydro-6,7-dimethyl-4-methylamino-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl ( E ) 6- ( l,3-dihydro-6-ethyl-7-methyl-4-methylamino-3- oxoisobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E ) 6- ( 6-cyclopropyl-l,3-dihydro-7-methyl-4-methylamino-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) 6- ( 1,3-dihydro-6-fluorovinyl-7-methyl-4-methylamino-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) 6- ( l,3-dihydro-7-methyl-4-methylamino-3-oxo-6- trifluorovinylisobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) 6- (l,3-dihydro-7-methyl-6- (prop-2-enyl) -4-methylamino-3- oxoisobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) 6- (l,3-dihydro-6-ethynyl-7-methyl-4-methylamino-3- oxoisobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) 6- (1,3-dihydro-7-methyl-6- (pent-2-ynyl) -4-methylamino-3- oxoisobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) 6- (6-allyl-l,3-dihydro-7-methyl-4-methylamino-3- oxoisobenzofuran-5-yl) -4-methyl-4-hexenoate; and methyl (E) 6- (1,3-dihydro-6- (4-methoxybenzyloxymethyl) -7-methyl-4- methylamino-3-oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate. 22C. Preparation of IE. varying Z Similarly, following the procedures of Example 22A above, but replacing methyl (E) -6- [l,3-dihydro-6-ethyl-7-methyl-4- (N-trifluoroacetyl-N-methyl)amino-3-oxoisobenzofuran-5-yl] -4-methyl-4- hexenoate with other compounds of Formula ID where Z is a sidechain of Formula ZA, ZB, ZC, ZD, ZE, ZF. ZG, or ZH, in which G is lower alkoxy, the following compounds of Formula IE where G is hydroxy and R 7 is ethyl are prepared: Formula IE where Z iε Sidechain ZA Formula IE where Z is Sidechain ZB Formula IE where Z is Sidechain ZE Formula IE where Z is Sidechain ZH EXAMPLE 23 ( E ) -2- .2- T2- ri.3-dihvdro-6-ethyl-4-hvdroχy-7-methyl- 3-oxoisobenzofur-uι-5-yllethylidenel cvclopent-l- (S) -yl.acetic acid 10A. Methyl ( E ) -6- ( 1.3-dihvdro-6-ethyl-4-hvdroxy-7-methyl-3- oxoiεobenzof"fan- ~-yl) -4-methyl-4-hexenoate A solution of (E) -6- ( l,3-dihydro-6-ethyl-4-hydroxy-7-methyl-3- oxoiεobenzofuran-5-yl) - -methyl-4-hexenoic acid in methanol (200 ml) waε treated with p-toluenesulfonic acid (0.8 g) and stirred at 25°C for 16 hourε. The reaction mixture was cooled to 0 β C. Methyl (E) -6- (1,3-dihydro- 6-ethyl-4-hydroxy-7-methyl-3-oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate, m.p. 116.5-117.6, was collected by filtration. 10B. Methyl (E) -6- (4-t-butyldimethylsilyloxy-l.3-dihvdro-6-ethyl-7-methyl- 3-oxoisobenzo uran-5-yl) -4-methyl-4-hexenoate A solution of methyl (E) -6- ( l,3-dihydro-6-ethyl-4-hydroxy-7-methyl-3- oxoisobenzofuran-5-yl) -4-methyl-4-hexenoate (8.61 g) and imidazole (3.5 g) in dimethyl formamide (40 ml) was treated with t-butyldi ethylsilyl chloride (4.50 g) and stirred at 25°C for 14 hourβ. The reaction mixture waε then poured into ice water and extracted with ether. Drying over magnesium sulfate and evaporation gave methyl (E) -6- (4-t-butyldimethyl- εilyloxy-1,3-dihydro-6-ethyl-7-methyl-3-oxoisobenzofuran-5-yl) -4-methyl-4- hexenoate. 10C. 2- (4-1-Butyldimethylsilyloxy-1.3-dihvdro-6-ethyl-7-methyl-3- oxoisobenzofuran-5-yl) -acetaldehyde A solution of methyl (E) -6- (4-t-butyldimethylεilyloxy-l,3-dihydro-6- ethyl-7-methyl-3-oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate (10.6 g) in methylene chloride (150ml) , methanol (150 ml) , and pyridine (5 ml) was treated with an excess of ozone at -70°C. The reaction was quenched with dimethylεulfide (20 ml) and εtirred for 5 hours at 25°C. The reaction mixture waε poured into IN aqueouε sodium hydrogen sulfate. Extraction with 1:1 ethyl acetate:hexane gave an oil which on purification by silica gel chromatography gave 2- (4-t-butyldimethylεilyloxy-l,3-dihydro-6-ethyl-7- methyl-3-oxoiεobenzofuran-5-yl) -acetaldehyde, m.p. 90.9-91.6°C. 10D. dl-1- .2- (4-1-Butyldimethylsilyloxy-1.3-dihvdro-6-ethyl-7-methyl-3- oxoisobenzofuran-5-yl) - -hydroxy-1-yll cyclopent-1-ene A solution of l-bromocyclopentene (21.4 g) in tetrahydrofuran (100 ml) waε added over 30 minuteε to magnesium (3.62 g) in tetrahydrofuran (30 ml) . The reaction mixture waε refluxed for 15 minuteε and then diluted with tetrahydrofuran εo that the final volume waε 200 ml. Thiε Grignard reagent (31 ml) waε then added to a solution of 2- (4-t-butyldimethyl- εilyloxy-1,3-dihydro-6-ethyl-7-methyl-3-oxoiεobenzofuran-5-yl) -acetaldehyde in tetrahydrofuran (100 ml) at -65°C. After 40 minuteε the reaction mixture waε poured into aqueouε ammonium chloride. Extraction with ether gave an oil which waε recryεtalized from t-butylmethyl ether/hexane to give dl-1- [2- (4-1-butyldimethylεilyloxy-1,3-dihydro-6-ethyl-7-methyl-3- oxoiεobenzofuran-5-yl) -1-hydroxy-1-yl] cyclopent-1-ene, m.p. 129.5-132°C. 10E. Cvclopentyl (4-1-butyldimethylsilyloxy-1,3-dihvdro-6-ethyl-7-methyl- 3-oxoisobenzofuran-5-yl methyl) methanone A solution of dimethyl εulfoxide (3 ml) in methylene chloride (100 ml) was cooled to -60°C and treated with trifluoroacetic anhydride ( 4 ml) . dl-1- [2- ( 4-t-Butyldimethylεilyloxy-l,3-dihydro-6-ethyl-7-methyl-3- oxoisobenzofuran-5-yl) -1-hydroxy-1-yl] cyclopent-l-ene (4.1 g) in methylene chloride (14 ml) waε added over 5 minuteε and the reaction mixture waε εtirred at -60°C for 1 hour. Triethylamine (11 ml) waε added and the reaction mixture was allowed to warm to 20°C. Aqueouε workup and extraction with methylene chloride, evaporation of the solvent, and crystallization of the reεidue from t-butylmethyl ether gave cyclopentyl (4-t-butyl-dimethylεilyloxy-1,3-dihydro-6-ethyl-7-methyl-3- oxoiεobenzofuran-5-yl methyl) methanone, m.p. 128.2-129.4°C. 10F. (S) -2- (4-1-Butyldimethylεilyloxy-1.3-dihvdro-6-ethyl-7-methyl-3- oxoisobenzofuran-5-yl) -1-cvclopentenyl-1-hvdroxyethane Cyclopentyl (4-1-butyldimethylεilyloxy-1,3-dihydro-6-ethyl-7-methyl- 3-oxoiεobenzofuran-5-yl methyl) methanone (4.2 g) waε treated with a 1M toluene εolution of (R) -tetrahydro-1-methyl-3,3-diphenyl-lH,3H-pyrrolo- [1,2-c] [1,3,2]oxazaborole (3 ml) . The toluene was evaporated in vacuo and methylene chloride added (2 ml) . The reaction mixture waε cooled to -30°C and borane/dimethyl εulfide (0.33 ml) was added three times at 45 minute intervalε. The reaction mixture waε stirred 16 hourε at -30°C and quenched by addition of 1M hydrogen chloride/ether (3 ml) . Toluene waε added (10 ml) and the εolution filtered, diluted with ether (200 ml) , waεhed with aqueous hydrochloric acid, aqueouε εodium bicarbonate and brine. Drying and evaporation gave an oil which waε purified by εilica gel chromatography to give (S) -2- (4-t-butyldimethylεilyloxy-l,3-dihydro-6-ethyl-7-methyl-3- oxoiεobenzofuran-5-yl) -1-cyclopentenyl-1-hydroxyethane. Further purification by cryεtallization from t-butylmethyl ether gave material with an enantiomeric excess of 97.8% (Chiracel OD-H, 85:15 hexane:i-propanol, 0.8 ml/minute, minor 8.3 minuteε, major 9.2 minutes) . 10G. Ethyl (S) (E) -2--f2- \2 - (4-t-butyldimethylsilyloxy-l,3-dihvdro-6-ethyl- 7-methyl-3-oxoisobenzofuran-5-yl)ethylidene] cvclopent-1-yl) acetate A mixture of (S) -2- (4-t-butyldimethylεilyloxy-l,3-dihydro-6-ethyl-7- methyl-3-oxoiεobenzofuran-5-yl) -1-cyclopentenyl-l-hydroxyethane (2.8 g) , pivalic acid (0.1 g) and triethyl orthoacetate (125 ml) waε heated to 138°C. After 2.5 hourε, more pivalic acid (65 mg) was added and the reaction waε continued 1 hour more. The reaction mixture waε cooled, the exceεε triethyl orthoacetate removed in vacuo, and the reεidue chromatographed on εilica gel (20% ethyl acetate/hexane) to give ethyl (S) (E) -2-{2- [2- (4-t-butyldimethylεilyloxy-l,3-dihydro-6-ethyl-7-methyl-3- oxoiεobenzofuran-5-yl)ethylidene] cyclopent-1-yl} acetate. 10H. Ethyl (S) (E) -2-(2- 12 - (1,3-dihvdro-6-ethyl- -hvdroxy-7-methyl-3- oxoiεobenzofuran-5-yl)ethylidene] cvclopent-1-yl) acetate A εolution of ethyl (S) (E) -2-{2- [2- (4-t-butyldimethylεilyloxy-l,3- dihydro-6-ethyl-7-methyl-3-oxoisobenzofuran-5-yl)ethylidene] cyclopent-1-yl} acetate (1.24 g) in tetrahydrofuran (8 ml) waε cooled to 0°C and treated with 1M tetrabutylammonium fluoride in tetrahydrofuran (3 ml) . After 5 minutes, the reaction mixture was poured into ice water and extracted with ethyl acetate. The extracts were dried, evaporated and the residue chromatographed on silica gel (20% ethyl acetate/hexane) to give ethyl (S) (E) -2-{2- [2- (l,3-dihydro-6-ethyl-4-hydroxy-7-methyl-3-oxoisobenzofuran- 5-yl)ethylidene] cyclopent-1-yl} acetate, m.p. 95.0-95.7°C. 101. (S) (E) -2- .2- [2 - (1.3-Dihvdro-6-ethyl-4-hvdroxy-7-methyl-3- oxoiBθbenzofuran-5-yl)ethylidene] cyclopent-l-yl. acetic acid A mixture of ethyl (S) (E) -2-{2- [2- (1,3-dihydro-6-ethyl-4-hydroxy-7- methyl-3-oxoiεobenzofuran-5-yl)ethylidene] cyclopent-1-yl} acetate (0.4 g) in methanol (20 ml) and water (20 ml) waε treated with lithium hydroxide (1.6 g) . The reaction mixture waε heated at 65°C for 2 hourε and then cooled. The methanol was removed in vacuo and the reεidue treated with exceεε 1M εodium hydrogen εulfate. Extraction with ethyl acetate followed by drying and evaporation gave a reεidue which waε recrystalized from t-butylmethyl ether to give (S) (E) -2-{2- [2- (l,3-dihydro-6-ethyl-4-hydroxy- 7-methyl-3-oxoisobenzofuran-5-yl)ethylidene] cyclopent-1-yl} acetic acid, m.p. 168.2-169.3°C with an enantiomeric excesε of 96.4% (Chiracel AD, 85:15 hexane:i-propanol, 0.1% trifluoroacetic acid, 0.8 ml/minute, minor 12.6 minuteε , maj or 13 .5 minuteε) . EXAMPLE 24 This example illustrateε the preparation of a representative pharmaceutical formulation for oral administration containing an active compound of Formula I, e.g., (E ) -6- ( 4-amino-l,3-dihydro-6-ethyl-7-methyl-3- oxoisobenzofuran-5-yl) -4-methyl-4-hexenoic acid. Ingredients Quantity per tablet, mgε. Active Compound 200 Lactose, spray-dried 148 Magnesium εtearate 2 The above ingredientε are mixed and introduced into a hard-εhell gelatin capsule. Other compoundε of Formula I, such as those prepared in accordance with Exampleε 15-23, can be uεed aε the active compound in the preparation of the orally adminiεtrable formulationε of thiε example. EXAMPLE 25 Thiε example illuεtrateε the preparation of another repreεentative pharmaceutical formulation for oral adminiεtration containing an active compound of Formula I, e.g., (E) -6- (4-amino-1,3-dihydro-6-ethyl-7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoic acid. Ingredientε Quantity per tablet, mgε. Active Compound 400 Cornstarch 50 Croscarmelloεe sodium 25 Lactose 120 Magnesium εtearate 5 The above ingredientε are mixed intimately and preεsed into single scored tabletε. Other compoundε of Formula I, εuch aε those prepared in accordance with Examples 15-23, can be used as the active compound in the preparation of the orally administrable formulations of thiε example. EXAMPLE 26 Thiε example illuεtrates the preparation of a representative pharmaceutical formulation containing an active compound of Formula I, e.g. , (E) -6- (4-amino-l,3-dihydro-6-ethyl-7-methyl-3-oxoisobenzofuran-5-yl) - 4-methyl-4-hexenoic acid. An oral suεpension iε prepared having the following compoεition. Ingredientε Active Compoimd Fu aric acid Sodium chloride Methyl paraben Propyl paraben Granulated εugar Sorbitol (70% εolution) Veegu K (Vanderbilt Co.) 1.0 g Flavoring 0.035 ml Coloringε 0.5 mg Distilled water q.s. to 100 ml — Other compounds of Formula I, such as thoεe prepared in accordance with Exaπpleε 15-23, can be uεed aε the active compound in the preparation of the orally adminiεtrable formulationε of this example. EXAMPLE 27 This example illustrateε the preparation of a repreεentative pharmaceutical formulation for oral adminiεtration containing an active compound of Formula I, e.g., (E) -6- ( 4-amino-l,3-dihydro-6-ethyl-7-methyl-3- cxoiεobenzofuran-5-yl) -4-methyl-4-hexenoic acid. An injectable preparation buffered to a suitable pH iε prepared having the following compoεition: Ingredientε Active Compound Sodium Acetate Buffer Solution (0.4 M) HCL (IN) or NaOH (IN) q.s. Water (diεtilled, sterile) q.s. Other compounds of Formula I, εuch aε thoεe prepared in accordance with Exampleε 15-23, can be uεed aε the active compound in the preparation of the injectable formulationε of thiε example. EXAMPLE 28 Thiε example illuεtrateε the preparation of a repreεentative pharmaceutical formulation for topical application containing an active compoimd of Formula I, e.g., ( E ) -6- ( 4-amino-l,3-dihydro-6-ethyl-7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoic acid. Ingredientε gramε Active compound 0.2-10 Span 60 2 Tween 60 2 Mineral oil 5 Petrolatum 10 Methyl paraben 0.15 Propyl paraben 0.05 BHA (butylated hydroxy aniεole) 0.01 Water q.ε. to 100 All of the above ingredientε, except water, are combined and heated to 60°C with εtirring. A εufficient quantity of water at 60°C iε then added with vigorouε εtirring to emulεify the ingredientε, and water then added q.ε. 100 g. Other compoundε of Formula I, εuch aε those prepared in accordance with Exampleε 15-23, can be uεed aε the active compound in the preparation of the topical formulationε of thiε example. EXAMPLE 29 Thiε example illustrates the preparation of a representative pharmaceutical formulation containing an active compound of Formula I, e.g. , (E) -6- (4-amino-l,3-dihydro-6-ethyl-7-methyl-3-oxoiεobenzofuran-5-yl) 4-methyl-4-hexenoic acid. A suppository totalling 2.5 grams is prepared having the following composition: Ingredients Active Compound 500 mg Witepsol H-15" balance ftriglycerides of saturated vegetable fatty acid; a product of Riches-Nelson, Inc., New York, N.Y.) Other compoundε of Formula I, εuch aε thoεe prepared in accordance with Exampleε 15-23, can be used as the active compound in the preparation of the εuppoεitory formulations of this example. EXAMPLE 30 Jn Vitro Determination of Therapeutic Activity (Aε an Anti-Inflammatory, Anti-Viral, Anti-Tumor, Anti-Pεoriatic and/or Immunoεuppreεεive Agent) Utilizing the Inhibition of IMP Dehydrogenaεe Asεay Thiε assay iε a modification of the method of Anderεon, J.H. and Sartorelli, A.C., Jour. Biol . Chem, 243:4762-4768 (1968) . It meaεureε the formation of NADH {λ mx = 340 nm, e340 = 6,220 M " 'cm"') aε Inosine 5' -monophosphate ("IMP") is converted to Xanthoεine 5' -monophoεphate ("XMP") by the human Type II IMP dehydrogenaεe ("IMPDH") . Compoundε are dissolved and diluted in DMSO, and reaction solutions containing compounds at 0, 0.01, 0.10, 1.0, 10, and lOOμM are prepared in diεposable methacrylic plaεtic microcuvetε ( 'UV-tranεparent' plaεtic, 1 cm pathlength, 1.5 ml capacity) . The solutions (0.5-1 ml) contain the following: 0.1 M TrisHCL, pH 8.0; 0.1 M KCL; 3.0 mM EDTA; 100 μg/ml BSA; 0.05 mM IMP; 0.10 mM NAD; 10% DMSO; 5-15 nM IMPDH (0.003-0.010 units/ml; one unit of enzyme catalyzes the formation of one μmol NADH per minute at 40°C at saturating εubεtrate concentrationε - 200 μM IMP and 400 μM NAD) . Reactionε are performed at 40°C and initiated by the addition of enzyme. Mycophenolic acid (IC J Q - 0.02μM) serves as the poεitive control. The reactionε are monitored at 340 nm for 10 minuteε in a UV/VIS spectrophotometer, and rate data are collected. The 50% inhibitory value ("ICV) is determined by fitting the fractional activities relative to control to the following equation on a Macintosh computer by the program Syεtat: Fractional activity = MAX/ ( (X/IC j o) n +l) . X iε the concentration of the compound, and the term n accountε for deviationε of the data from a εiπrple competitive inhibition model. The compounds of the present invention inhibit IMPDH when tested by this method, indicating their activity aε anti-inflammatory, anti-viral, anti-tumor, anti-pεoriatic and/or immunoεuppreεεive agentε. EXAMPLE 31 In Vitro Determination of Immunoεuppreεεive Activity Utilizing Reεponεes of Human Peripheral Blood Lymphocytes to T- and B-cell Mitogens Thiε procedure iε a modification of a procedure initially deεcribed by Greaveε, et al. ["Activation of human T and B lymphocyteε by polyclonal itogenε," Nature, 248:698-701 (1974)] . Human mononuclear cellε ("PBL") are separated from heparinized whole blood by density gradient centrifugation in Ficoll-Plaque (Pharmacia) . After washing, 2 x 10 5 cells/well are cultured in microtiter plates with RPMI 1640 supplemented with 5% fetal calf serum, penicillin and streptomycin. PHA (Sigma) at 10 μg/ml is then added. Teεt materials are tested at concentrations between 10 4 and lO'M, by addition to the culture at time 0. Cultureε are set up in quadruplicate and incubated at 37°C in a humidified atmoεphere with 7% C0 2 for 72 hours. A pulse of 0.5 μCi/well of ^-thymidine is added for the last 6 hours. Cells are collected on glasε fiber filterε with an automatic harveεter and radioactivity is measured by standard scintillation procedureε. The 50% inhibitory concentration ("IC JO ") for mitogenic εtimulation iε determined graphically. The compoundε of the present invention show immunosuppreεεive activity when tested by this method. EXAMPLE 32 Determination of Immunosuppresεive Activity Utilizing the Hemolvtic Plaσue Forming Cell Aεsav Thiε procedure iε a modification of "The agar plaque technique for recognizing antibody producing cellε," a procedure initially deεcribed by Jerne et al. , [Cellbound Antibodies, Amoε and Kaprowεki editorε (Wiεtar Inεtitute Preεε, Philadelphia, 1963), p.' 109] . Groupε of 5-6 adult C578B1/6 male mice were εenεitized with 1X10 8 εheep red blood cellε ("SRBC") and εimultaneouεly treated with an oral doεage form of the teεt material in an aqueouε vehicle. Animalε in a control group receive the same volume of vehicle. Four dayε after SRBC inoculation, εpleenε are diεperεed in looεe Ten Broeck homogenizerε. The number of nucleated cellε ("WBC") iε determined and the εpleen cell εuεpension iε mixed with SRBC, guinea pig complement and agar εolution at 0.5% concentration. Aliquotε of the above mixture (0.1 ml) are dropped on four εeparate quadrantε of a Petri dish and are covered with cover slips. After two hours incubation at 37°C, areas of hemolyεiε around plaque-forming cellε ("PFC") are counted with a diεεecting microεcope. Total WBC/εpleen, PFC/εpleen and PFC/10* WBC ("PPM") are calculated for each mouεe εpleen. Geometric meanε of each treatment group are then compared with the vehicle-treated control group. The compounds of the present invention show immunosuppreεεive activity when teεted by thiε method. While the present invention has been described with reference to the specific embodiments thereof, it should be understood by thoεe εkilled in the art that variouε changeε may be made and equivalentε may be εubεtituted without departing from the true spirit and scope of the invention. In addition, many modifications may be made to adapt a particular situation, material, composition of matter, process, process step or steps, to the objective, spirit and scope of the present invention. All such modifications are intended to be within the scope of the claims appended hereto.

Claims: WHAT IS CLAIMED IS : 1 . A compound represented by the formula : wherein: R 1 is hydrogen or lower alkyl; R 2 is hydrogen, lower alkyl, -C(0)R 3 , -CfOjOTΛ. 3 , -C0 2 R 6 , or -S0 2 R 3 ; in which: R 3 is hydrogen, lower alkyl, halo lower alkyl or optionally substituted phenyl; R 4 is hydrogen, lower alkyl or optionally εubεtituted phenyl; R 3 is hydrogen, lower alkyl or optionally substituted phenyl; R* is lower alkyl or optionally substituted phenyl; and R 7 iε lower alkyl, cycloalkyl, fluorovinyl, difluorovinyl, trifluorovinyl, lower alkenyl, -OsC-R 8 , allyl, CHO, or CH,OR 9 ; in which: R 8 iε hydrogen or lower alkyl, and R 9 iε hydrogen or 4-methoxybenzyl; and Z is a side chain selected from Formulae ZA, ZB, ZC, ZD, ZE, ZF, ZG, and ZH: Formula ZA wherein: Z' is hydrogen, lower alkyl, halo or CF,; Z 2 is hydrogen, lower alkyl, lower alkoxy, aryl, or -CH,Z 13 , where Z 13 is aryl or heteroaryl; Z 3 is hydrogen, lower alkyl, lower alkenyl, lower alkoxy, phenyl, or -S(0) m Z 12 , where Z 12 is lower alkyl, and is 0, 1 or 2; Z 4 is hydrogen, lower alkyl, or phenyl, or Z 3 and Z 4 taken together with the carbon to which they are attached •149- form cycloalkyl of three to five carbon atoms; and G is OH, lower alkoxy, lower thioalkyl, -NG'G 2 , -0(CH,) π NG'G 2 , or - 0(-_H,).N=G 3 , where n is an integer from.l to 6, G 1 is hydrogen or lower alkyl, G 2 is hydrogen or lower alkyl, and =G 3 is lower alkylene of four to εix carbon atomε, or lower alkylene of three to five carbon atomε pluε one member that is -0-, -S-, or -N(G 4 )- where G 4 iε hydrogen or lower alkyl; Formula ZB wherein: Z 3 iε hydrogen or lower alkyl; Z 8 iε hydrogen or lower alkyl; D 1 and D 2 together with their adjacent carbon atomε form an optionally εubεtituted, εaturated or unεaturated carbocyclic or heterocyclic ring of 3 to 7 atomε; and G iε aε defined above; or Formula ZC wherein: Z 3 , Z 8 , and G are as defined above; or Formula ZD wherein: D 3 iε -CIV or -CHjCH,- ; and G is as defined above; or Formula ZE wherein: Z* is hydrogen, lower alkyl, lower alkoxy, -COOH, -NH, or halo; Z 7 is hydrogen, lower alkyl, lower alkoxy or halo; and Z 3 and G are as defined above; or Formula ZF wherein: Z 1 and G are as defined above; or Formula ZG wherein: D 3 , Z 2 , Z 3 , Z 4 and G are as defined above; or Formula ZH wherein: D 4 is -CH 2 -, -CH,CH,-, -CH 2 CH,CH 2 -, -0-, or -OCH 2 - ; and Z 1 and G are as defined above; or a pharmaceutically acceptable salt thereof. 2. The compound or salt of Claim 1 wherein Z is selected from Formulae ZA, ZB, ZE and ZH. 3. The compound or salt of Claim 1 wherein R 1 is hydrogen and R 2 is hydrogen or -C(0)CF,. 4. The compound or salt of Claim 3 wherein G is OH. 5. The compound or salt of Claim 4 where R 7 is methyl, ethyl, vinyl or cyclopropyl. 6. The compound or εalt of Claim 3 wherein G is morpholinoethoxy. 7. The compound or salt of Claim 1 comprising a εingle enantiomer, a diastereomer, a racemic mixture or a non-racemic mixture. 8. The compound or εalt of Claim 5 wherein Z iε a εide chain of Formula ZA. 9. The compound or εalt of Claim 8 wherein: Z 1 iε methyl; Z 2 is hydrogen; Z 3 is hydrogen; Z 4 iε hydrogen and R 7 is ethyl, namely (E) -6- (4- amino-1,3-dihydro-6-ethyl-7-methyl-3-oxoisobenzofuran-5-yl) -4-methyl-4- hexenoic acid. 10. The compound or εalt of Claim 4 wherein Z iε a εide chain of Formula ZB. 11. The compound or salt of Claim 10 wherein Z 3 and Z 8 are H, D'-D 2 is -(CH,),-, R 2 is hydrogen, and R 7 is ethyl, namely (E) -2-{2- [2- (4-amino- 1,3-dihydro-6÷ethyl-7-methyl-3-oxoisobenzofuran-5-yl) -ethylidene] - cyclopent-1-yl}acetic acid. 12. The compound or εalt of Claim 4 wherein Z iε a εide chain of Formula ZE. 13. The compound or εalt of Claim 12 wherein Z 5 and Z 7 are hydrogen, and Z 6 is hydrogen or lower alkyl. 14. The compound or salt of Claim 4 wherein Z iε a side chain of Formula ZH. 15. The compound or salt of Claim 14 wherein Z 1 is lower alkyl. 16. The compound or εalt of Claim 15 wherein D 4 iε -CH 2 -, -CH 2 CH 2 -, or -0CH 2 - . 17. A pharmaceutical composition comprising a pharmaceutically acceptable non-toxic excipient and a therapeutically effective amount of a compound of Claim 1, or a pharmaceutically acceptable εalt thereof. 18. A method of treatment for immune, inflammatory, tumor, proliferative, viral or psoriatic diεorderε in a mammal, co priεing adminiεtering a therapeutically effective amount of a compound or εalt of Claim l to a mammal in need thereof. 19. A proceεs for preparing compounds of Formula I, wherein: R 1 iε hydrogen or lower alkyl; R 2 iε hydrogen, lower alkyl, -C(0)R 3 , -C(0)NR 4 R 5 , -CO,R 6 , or -S0 2 R 3 ; in which: R 3 iε hydrogen, lower alkyl, halo lower alkyl or optionally εubεtituted phenyl; R 4 iε hydrogen, lower alkyl or optionally εubεtituted phenyl; R 3 iε hydrogen, lower alkyl or optionally εubεtituted phenyl; R 6 iε lower alkyl or optionally εubεtituted phenyl; and R 7 iε lower alkyl, cycloalkyl, fluorovinyl, difluorovinyl, trifluorovinyl, lower alkenyl, -C≡C-R 8 , allyl, CHO, or CH 2 OR 9 ; in which: R 8 iε hydrogen or lower alkyl, and R 9 iε hydrogen or 4-methoxybenzyl; and Z iε a εide chain εelected from Formulae ZA, ZB, ZC, ZD, ZE, ZF, ZG, and ZH: Formula ZA wherein: Z l is hydrogen, lower alkyl, halo or CF,; Z 2 is hydrogen, lower alkyl, lower alkoxy, aryl, or -CI^Z' 3 , where Z 13 iε aryl or heteroaryl; Z 3 iε hydrogen, lower alkyl, lower alkenyl, lower alkoxy, phenyl, or -S(0) m Z 12 , where Z 12 iε lower alkyl, and m iε 0, 1 or 2; Z 4 iε hydrogen, lower alkyl, or phenyl, or Z 3 and Z 4 taken together with the carbon to which they are attached form cycloalkyl of three to five carbon atomε; and G iε OH, lower alkoxy, lower thioalkyl, -NG'G 2 , -0(CH 2 ) n NG'G 2 , or - 0(CH 2 )_N=G 3 , where n is an integer from 1 to 6, G 1 is hydrogen or lower alkyl, G 2 iε hydrogen or lower alkyl, and =G 3 iε lower alkylene of four to εix carbon atomε, or lower alkylene of three to five carbon atomε pluε one member that is -0- , -S-, or -N(G 4 ) - where G 4 is hydrogen or lower alkyl; Formula ZB wherein: Z 5 iε hydrogen or lower alkyl; Z 8 iε hydrogen or lower alkyl; D 1 and D 2 together with their adjacent carbon atomε form an optionally εubεtituted, εaturated or unεaturated carbocyclic or heterocyclic ring of 3 to 7 atomε; and G iε aε defined above; or Formula ZC wherein: Z 3 , Z 8 , and G are aε defined above; or Formula ZD wherein: D 3 iε -CH 2 - or -CH 2 CH 2 - ; and G iε aε defined above; or Formula ZE wherein: Z 6 iε hydrogen, lower alkyl, lower alkoxy, -COOH, -NH 2 or halo; Z 7 iε hydrogen, lower alkyl, lower alkoxy or halo; and Z 3 and G are as defined above; or Formula ZF wherein: Z 1 and G are aε defined above; or Formula ZG wherein: D 3 , Z 2 , Z 3 , Z 4 and G are aε defined above; or Formula ZH wherein: D 4 is -CH--, -CH J CH J -, -CH 2 CH,CH,-, -0-, or -OCH 2 -; and Z ! and G are aε defined above; and the pharmaceutically acceptable εaltε thereof; which comprises a) reacting a compound of Formula I wherein G is lower alkoxy, lower thioalkyl, NG'G 2 , 0- (CH^.-NG'G 2 , or -0- (CH 2 ) n -N=G 3 , in which n, G 1 , G 2 , and G 3 are as defined above, with an inorganic baεe to form a compound of Formula I wherein G iε hydroxy; or b) reacting a compound of Formula I wherein G iε hydroxy, with a compound of the formula GH, wherein G iε lower alkoxy, lower thioalkyl, NG'G 2 , O- (CH 2 ) n -NG'G 2 , or O- (CH 2 ) n -N=G 3 , in which n, G 1 , G 2 , and G 3 are aε defined above, to form a compound of Formula I wherein G iε lower alkoxy, lower thioalkyl, NG'G 2 , O- (CH 2 ) n -NG'G 2 , or O- (CH 2 )_-N=G 3 , in which n, G 1 , G 2 , and G 3 are aε defined above; or c) reacting a compound of Formula I R 1 iε hydrogen and R 2 is-C(0)R 3 wherein R 3 is hydrogen, and G is lower alkoxy, with a compound of the formula HNR 4 R 5 , where R 4 and R 5 are independently hydrogen, lower alkyl or optionally εubεtituted phenyl, to form a compound of Formula I wherein R 1 iε hydrogen and R 2 iε-C(0)NR 4 R 3 wherein R 4 and R 5 are independently hydrogen, lower alkyl or optionally εubεtituted phenyl; or d) reacting a compound of Formula I wherein R 1 and R 2 are both hydrogen, and G iε lower alkyl, optionally substituted phenyl, or - (CH 2 ) m -N=Y, with _. compound of the formula (R 3 C(0)) 2 0 or R 3 C (0) Cl wherein R 3 iε as defined above, to form a compound of Formula I wherein R 2 is -C(0)R 3 , where R 3 is lower alkyl, halo lower alkyl or optionally subεtituted phenyl; or e) reacting a compound of Formula I wherein R 1 iε hydrogen, R 2 is - C(0)R 3 wherein R 3 is aε defined above and G iε lower alkoxy, with a compound of the formula R'x, where R' iε lower alkyl and X is iodine or bromine, to form a compound of Formula I wherein R 1 is lower alkyl; or f) converting a free compound of Formula I to a pharmaceutically acceptable εalt of a compound of Formula I; or g) converting a pharmaceutically acceptable εalt of a compound of Formula I to the free compound of Formula I; or h) converting a pharmaceutically acceptable εalt of a compound of Formula I to another pharmaceutically acceptable εalt of a compound of Formula I.

Inventors: ANDRADE FIDENCIO F, ARTIS DEAN R, ELWORTHY TODD R, GARCIA ALICIA C, HAWLEY RONALD C, HERNANDEZ MARIA T L, LOUGHHEAD DAVID G, MARTIN TERESA A T, MORGANS DAVID J JR, MURRA FRANCISCO X T, NELSON PETER H, PATTERSON JOHN W JR, SJOGREN ERIC B, SMITH DAVID B, WALTOS ANN MARIE, WEIKERT ROBERT J, ZERTUCHE MARIO F, ANDRADE, FIDENCIO, F., ARTIS, DEAN, R., ELWORTHY, TODD, R., GARCIA, ALICIA, C., HAWLEY, RONALD, C., HERNANDEZ, MARIA, T., L., LOUGHHEAD, DAVID, G., MARTIN, TERESA, A., T., MORGANS, DAVID, J., JR., MURRA, FRANCISCO, X., T., NELSON, PETER, H., PATTERSON, JOHN, W., JR., SJOGREN, ERIC, B., SMITH, DAVID, B., WALTOS, ANN, MARIE, WEIKERT, ROBERT, J., ZERTUCHE, MARIO, F.
Applicants: SYNTEX INC, SYNTEX (U.S.A.) INC.
Application year: 1995
Main classification: C07D307
IPC codes: A61K31, A61P17, A61P29, A61P35, A61P37, C07D307, C07D405, C07D407, C07D409