ANTIPICORNAVIRAL COMPOUNDS AND COMPOSITIONS, THEIR PHARMACEUTICAL USES, AND MATERIALS FOR THEIR SYNTHESIS

Abstract: Compounds of the formula (I) where the formula variables are as defined in the disclosure, advantageously inhibit or block the biological activity of the picornaviral 3C protease. These compounds, as well as pharmaceutical compositions containing these compounds, are useful for treating patients or hosts infected with one or more picornaviruses, such as RVP. Intermediates and synthetic methods for preparing such compounds are also described.

Description: TITLE A-NTMCORNNNIRAL COMPOUNDS AND COMPOSITIONS, THEIR PHARMACEUTICAL USES, AND MATERIALS FOR THEIR SYNTHESIS BACKGROUND OF THE INVENTION Field ofthe Invention The invention relates to pyrrole-containing peptidomimetic compounds that inhibit the enzymatic activity of picomaviral 3C proteases, especially rhinovirus 3C proteases (RVPs), and that retard viral growth in cell culture. The invention also relates to the use of these compounds in pharmaceutical compositions, methods of treatment of rhino viral infections using these compounds and compositions, and processes for the synthesis of these compounds and compounds useful in the syntheses thereof. Related Background Art The picornaviruses are a family of tiny non-enveloped positive-stranded RNA-containing viruses that infect humans and other animals. These viruses include the human rhinoviruses, human polioviruses, human coxsackieviruses. human echoviruses, human and bovine enteroviruses, encephalomyocarditis viruses, meningitis virus, foot and mouth viruses, hepatitis A virus, and others. The human rhinoviruses are a major cause ofthe common cold. To date, there are no effective therapies on the market that cure the common cold, only treatments that relieve the symptoms. Picomaviral infections may be treated by inhibiting the proteolytic picomaviral 3C enzymes. These enzymes are required for the natural maturation of the picomaviruses. They are responsible for the autocatalytic cleavage ofthe genomic, large polyprotein into the essential viral proteins. Members ofthe 3C protease family are cysteine proteases, where the sulfhydryl group most often cleaves the glutamine-glycine amide bond. Inhibition of 3C proteases is believed to block proteolytic cleavage ofthe viral polyprotein, which in rum can retard the maturation and replication ofthe viruses by interfering with viral particle production. Therefore, inhibiting the processing of this cysteine protease with selective small molecules that are specifically recognized should represent an important and useful approach to treat and cure viral infections of this nature and, in particular, the common cold. Some small-molecule inhibitors ofthe enzymatic activity of picomaviral 3C proteases (i.e., antipicornaviral compounds) have been recently discovered. See, for example: U.S. Patent No. 5,856,530; U.S Patent No. 5,962,487; U.S. Patent No. 6,020,371; and U.S. Patent Application No. 09/301,977, filed April 29, 1999, by Dragovich et al. See also: Dragovich et al., "Structure-Based Design, Synthesis, and Biological Evaluation of Irreversible Human Rhinovirus 3C Protease Inhibitors . . . ," J. Med. Chem. (1999), Vol. 42, No. 7, 1203-1212, 1213-1224; and Dragovich et al., "Solid-phase Synthesis of Irreversible Human Rhinovims 3C Protease Inhibitors . . . ," Bioorg. & Med. Chem. (1999), Vol. 7, 589-598. There remains a desire, to discover small-molecule compounds that are especially potent antipicornaviral agents. Inhibitors of other related cysteine proteases such as cathepsins have been described in, e.g., U.S. Patent No. 5,374,623; U.S. Patent No. 5,498,616; and WIPO International Publication Nos. WO 94/04172, WO 95/15749, WO 97/19231, and WO 97/49668. There yet remains a need for inhibitors targeting the picomaviral 3C cysteine protease with desirable pharmaceutical properties, such as high specificity, good therapeutic index or low toxicity. SUMMARY OF THE INVENTION This invention relates to compounds useful for inhibiting the activity of picomaviral 3C proteases having the general Formula I: wherein: R is an alkylcarbonylalkyl, cycloalkylcarbonylalkyl, arylcarbonylalkyl, heteroarylcarbonylalkyl, alkylcarbonylaminoalkyl, cycloalkylcarbonylaminoalkyl, heterocycloalkylcarbonylaminoalkyl, arylcarbonylaminoalkyl, heteroarylcarbonylaminoalkyl, alkylaminocarbonylalkyl, cycloalkylaminocarbonylalkyl, heterocycloalkylaminocarbonylalkyl, arylaminocarbonylalkyl, heteroarylaminocarbonylalkyl group, where each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl moiety thereof is unsubstituted or substituted with one or more suitable substituents; R is H or an alkyl group, unsubstituted or substituted with one or more suitable substituents; R d is H, halo, hydroxyl, or an alkyl, alkoxy or alkylthio group, where the alkyl, alkoxy or alkylthio group is unsubstituted or substituted with one or more suitable substituents; R c is a moiety having the formula: R e and R are each independently H or a lower alkyl group; m is 0 or 1, provided that when m is 1, R a is not an amino-substituted alkylcarbonylalkyl or amino-substituted alkylcarbonylaminoalkyl group, and when m is 0, R a is selected from an alkylaminocarbonylalkyl, cycloalkylaminocarbonylalkyl, heterocycloalkylaminocarbonylalkyl, arylaminocarbonylalkyl, heteroarylaminocarbonylalkyl and heteroarylcarbonylaminoalkyl group, provided that R a is not substituted indolecarbonylaminoalkyl; p is an integer of from 0 to 5; A, is CH or N; when p is 1, 2, 3, 4, or 5, A 2 is C(R 8 )(R h ), N(R f ), S, S(O), S(O) 2 , or O, and when p is 0, A 2 is C(R g )(R h )(R i ), ^R 6 )^), S^ 8 ), S O)^ 8 ), S(O) 2 (R ), or O Et 8 ), where each R 8 , R h and R 1 is independently H or a lower alkyl group; each A 3 present is each independently C(R 8 )(R h ), N(R f ), S, S(O), S(O) 2 , or O, where each R 8 , R h and R 1 is independently H or a lower alkyl group; when p is 1, 2, 3, 4, or 5, A 4 is N(R j ), C(R g )(R h ), or O, and when p is 0 (i.e., A 3 is not present), A 4 is C(R g )(R h )(R i ), and OCR 1 ), where each R g , R h and R 1 is independently H or a lower alkyl group, each R J is H, an alkyl, aryl, or acyl group, and each R k is H or an alkyl or aryl group; provided that no more than two heteroatoms occur consecutively in the above-depicted ring formed by A l5 (A 2 ) m , (A 3 ) p , A 4 , and C=O, where each dotted line in the ring depicts a single bond when A 2 is present (i.e., m = 1) and a hydrogen atom when A 2 is absent (i.e., m = 0); and Z and Z 1 are each independently H, F, an alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl group, where the alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl group is unsubstituted or substituted with one or more suitable substituents, -C^R 1 , -CO^ 1 , -CN, -C(0)m}R m , -C^NR'OR 1 ", -C^R 1 , -C(S)OR' -C(S)NR 1 R m , -C(=NR 1 )R m , -C(=NR , )OR m , -NO 2 , -SOR m , -SO 2 R\ -SO 2 NR 1 R m , -SO 2 (NR 1 )(OR m ), -SONR 1 , -SO 3 R 1 , -PO(OR ! ) 2 , -PO(OR , )(OR m ) > -POtN ^XOR") , -PO(NR 1 R m )( R n R°), -C(O)NR 1 NR m R n , -C(S)NR 1 NR m R n , where R 1 , R m , R n and R° are each independently H or an alkyl, cycloalkyl, aryl, heterocycloalkyl, acyl or thioacyl group, where the alkyl, cycloalkyl, aryl, heterocycloalkyl, acyl or thioacyl group is unsubstituted or substituted with one or more suitable substituents, or where any two ofthe R 1 , R m , R and R°, taken together with the atoms to which they are bonded, form a heterocycloalkyl group, which may be optionally substituted, or Z and R d , together with the atoms to wliich they are bonded, form a cycloalkyl or heterocycloalkyl group, where Z and R d are as defined above except for moieties that cannot form the cycloalkyl or heterocycloalkyl group, or Z and Z 1 , together with the atoms to wliich they are bonded, form a cycloalkyl or heterocycloalkyl group, where Z and Z 1 are as defined above (except for moieties that cannot form the cycloalkyl or heterocycloalkyl group); or a prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate of said compound. i another embodiment ofthe compounds ofthe above Formula I, N is CH orN; A 2 is C(R g )(R h ), N(R), S, S(O), S(O) 2 , or O, where each R , R h and R f is independently H or a lower alkyl group; each A 3 present is independently C(R ε )(R h ), N(R), S, S(O), S(O) 2 , or O, where each R g , R h and R 1 is independently H or a lower alkyl group; when p is 1 , 2, 3 , 4, or 5 , A 4 is N(R j ), C(R g )(R h ), or O, and when p is 0, A 4 is N(R j )(R k ), C(R 8 )(R h )(R i ), and OtR ), where each R g , R h and R 1 is independently H or a lower alkyl group, each R J is H, an alkyl, aryl, or acyl group, and each R k is H or an alkyl or aryl group; provided that no more than two heteroatoms occur consecutively in the above-depicted ring formed by A l5 (A 2 ) m , (A 3 ) p , A 4 , and C=O, where each dotted line in the ring depicts a single bond when A 2 is present and a hydrogen atom when A 2 is absent; and Z and Z 1 are each independently H, F, an alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl group, where the alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl group is unsubstituted or substituted with one or more suitable substituents, -0(0)^, -CO^ 1 , -CN, -C(O)NR 1 R m , -C(O)NR 1 OR m , -C^R 1 , -C(S)NR 1 R m , -NO 2 , -SOR m , -SO a R 1 , -SO 2 NR 1 R m , -SO 2 (NR 1 )(OR m ), -SONR 1 , -SO 3 R 1 , -PO(OR') 2 , -PO OR'XOR" 1 ) , -PO NR^XOR 11 ) , -PO(NR 1 R m )(NR n R°), -C^N 'NR R", -C(S)NR'NR m R n , where R 1 , R m , R n and R° are each independently H, an alkyl, cycloalkyl, aryl, heterocycloalkyl, acyl or thioacyl group, where the alkyl, cycloalkyl, aaryl, heterocycloalkyl, acyl or thioacyl group is unsubstituted or substituted with one or more suitable substituents, or where any two ofthe R 1 , R , R and R°, taken together with the atoms to which they are bonded, form a heterocycloalkyl group, which is unsubstituted or substituted with one or more suitable substituents, or Z and Z 1 , together with the atoms to which they are bonded, form a cycloalkyl or heterocycloalkyl group, where Z and Z 1 are as defined above. One embodiment of this invention relates to compounds useful for inhibiting the activity of picomaviral 3C proteases having the following general Formula II: π wherein R a' is an alkyl, cycloalkyl, aryl or heteroaryl group, where the alkyl, cycloalkyl, aryl or heteroaryl group is unsubstituted or substituted with one or more suitable substituents, n is 1, 2 or 3, m is 1, R x and R y are each independently selected from H and an alkyl group, unsubstituted or substituted with one or more suitable substituents, and R b , R°, R d , Z and Z 1 are as defined above, provided that R a ' is not an amino-substituted alkyl group. Another embodiment of this invention relates to compounds useful for inhibiting the activity of picomaviral 3C proteases having the following general Formula HI: m wherein R a ' is an alkyl, cycloalkyl, aryl or heteroaryl group, where the alkyl, cycloalkyl, aryl or heteroaryl group is unsubstituted or substituted with one or more suitable substituents, n is 1, 2 or 3, m is 1, R x and R y are each independently selected from H and an alkyl group, unsubstituted or substituted with one or more suitable substituents, and R b , R c , R d , Z and Z 1 are as defined above, provided that R a ' is not an amino-substituted alkyl group. This invention also relates to compounds useful for inhibiting the activity of picomaviral 3C proteases having the following general Formula IV: IV wherein R a' is an alkyl, aryl, cycloalkyl, heterocycloalkyl or heteroaryl group, where the alkyl, aryl, cycloalkyl, heterocycloalkyl and heteroaryl group is unsubstituted or substituted with one or more suitable substituents, n is 1, 2 or 3, R x and R y are each independently selected from H and an alkyl group, unsubstituted or substituted with one or more suitable substituents, and R b , R°, R d , Z and Z 1 are as defined above. This invention relates to compounds useful for inhibiting the activity of picomaviral 3C proteases having the general Formula V: V wherein: W is CH orN; R 1 is H, halo or an alkoxy, alkyl, aryl, cycloalkyl, heterocycloalkyl or heteroaryl group, where the alkoxy, alkyl, aryl, cycloalkyl, heterocycloalkyl and heteroaryl group is unsubstituted or substituted with one or more suitable substituents; R 2 and R 3 are each independently H, halo or an alkoxy or lower alkyl group, where the alkoxy or lower alkyl group is unsubstituted or substituted with a suitable substituent; or R 1 together with R 2 form a cycloalkyl, heterocycloalkyl, aryl or heteroaryl ring, where the cycloalkyl, heterocycloalkyl, aryl or heteroaryl ring is unsubstituted or substituted with a suitable substituent; R 4 and R 6 are each independently H or a lower alkyl group, unsubstituted or substituted with a suitable substituent; R 5 is H or an alkyl group, unsubstituted or substituted with a suitable substituent; R 7 is a moiety having the formula: wherein: R 8 and R 9 are each independently H or a lower alkyl group; m is 0 or 1, provided that when W is N, m is 0 and R 1 together with R 2 form an aryl ring, the aryl ring is unsubstituted (e.g., R 1 together with R 2 and the pyrrole to which they are bound do not form a substituted indole); p is an integer of from 0 to 5; A, is CH orN; when p is 1, 2, 3, 4, or 5, A 2 is C(R 10 )(R n ), N(R 12 ), S, S(O), S(O) 2 , or O, and when p is 0, A 2 is C(R 10 )(R π )(R 12 ), N(R 10 )(R 12 ), S(R 10 ), S(O)(R 10 ), S(O) 2 (R 10 ), or O(R 10 ) where each R 10 , R 11 and R 12 is independently H or a lower alkyl group; each A 3 present is independently C(R 10 )(R π ), N(R 12 ), S, S(O), S(O) 2 , or O, where each R 10 , R π and R 12 is independently H or a lower alkyl group; when p is 1, 2, 3, 4, or 5, A 4 is N(R 13 ), C(R 10 )(R n ), or O, and when p is 0, A 4 is N(R 13 )(R 14 ), C(R 10 )(R n )(R 12 ), and O(R 14 ), where each R 10 , R 11 and R 12 is independently H or a lower alkyl group, each R 13 is H or an alkyl, aryl, or acyl group, and each R 14 is H or an alkyl or aryl group; provided that no more than two heteroatoms occur consecutively in the above-depicted ring formed by A l5 (A 2 ) m , (A 3 ) p , A 4 , and C=O, where each dotted line in the ring depicts a single bond when A 2 is present and a hydrogen atom when A 2 is absent; and Z and Z 1 are each independently H, F, an alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl group, where the alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl group is unsubstituted or substituted with one or more suitable substituents, -C(O)R 15 , -CO 2 R 15 , -CN, -C(O)NR 15 R 16 , -C(O)NR 15 OR 16 , -C(S)R 15 , -C(S)OR 15 , -C(S)NR 15 R 16 , -C(=NR 15 )R 16 , -C(=NR 15 )OR 16 , -NO 2 , -SOR 16 , -SO 2 R 15 , -SO 2 NR 15 R 16 , -SO 2 (NR 15 )(OR 16 ), -SONR 15 , -SO 3 R 15 , -PO(OR 15 ) 2 , -PO(OR 15 )(OR 16 ) ; -PO(NR 15 R 16 )(OR 17 ) ; -PO(NR 15 R 16 )(NR 17 R 18 ), -C(O)NR 15 NR 16 R 17 , -C(S)NR 15 NR 16 R 17 , where R 15 , R 16 , R 17 and R 18 are each independently H or an alkyl, cycloalkyl, aryl, heterocycloalkyl, acyl or thioacyl group, where the alkyl, cycloalkyl, aryl, heterocycloalkyl, acyl or thioacyl group is unsubstituted or substituted with one or more suitable substituents, or where any two ofthe R 15 , R 16 , R 17 and R 18 , taken together with the atoms to which they are bonded, form a heterocycloalkyl group, which is unsubstituted or substituted with one or more suitable substituents, or Z and Z 1 , together with the atoms to which they are bonded, form a cycloalkyl or heterocycloalkyl group, where Z and Z 1 are as defined above (except for moieties that cannot form the cycloalkyl or heterocycloalkyl group). In another embodiment of the compounds of Formula V, A 2 is C(R 10 )(R π ), N(R 12 ), S, S(O), S(O) 2 , or O, where each R 10 , R" and R 12 is independently H or a lower alkyl group; each A 3 present is independently C(R 10 )(R n ), N(R 12 ), S, S(O), S(O) 2 , or O, where each R'°, R 11 and R 12 is independently H or a lower alkyl group; when p is 1, 2, 3, 4, or 5, A 4 is N(R 13 ), C(R 10 )(R n ), or O, and when p is 0, A 4 is N(R 13 )(R 14 ), C(R 10 )(R U )(R 12 ), and O(R 14 ), where each R 10 , R n and R 12 is independently H or a lower alkyl group, each R 13 is H or an alkyl, aryl, or acyl group, and each R 14 is H or an alkyl or aryl group; provided that no more than two heteroatoms occur consecutively in the above-depicted ring formed by A l5 (A 2 ) m , (A 3 ) p , A 4 , and C=O, where each dotted line in the ring depicts a single bond when A 2 is present and a hydrogen atom when A 2 is absent; and Z and Z 1 are each independently H, F, an alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl group, where the alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl group is unsubstituted or substituted with one or more suitable substituents, -C(O)R 15 , -CO 2 R 15 , -CN, -C(O)NR 15 R 16 , -C(O)NR 15 OR 16 , -C(S)R 15 , -C(S)NR 15 R 16 , -NO 2 , -SOR 16 , -SO 2 R 15 , -SO 2 NR 15 R 16 , -SO 2 (NR 15 )(OR 16 ), -SONR 15 , -SO 3 R 15 , -PO(OR 15 ) 2 , -PO(OR 15 )(OR 16 ) ; -PO(NR 15 R 16 )(OR 17 ) > -PO(NR 15 R 16 )(NR 17 R 18 ), -C(O)NR 15 NR 16 R 17 , -C(S)NR 15 NR 16 R 17 , where R 15 , R 16 , R 17 and R 18 are each independently H or an alkyl, cycloalkyl, aryl, heterocycloalkyl, acyl or thioacyl group, where the alkyl, cycloalkyl, aryl, heterocycloalkyl, acyl or thioacyl group is unsubstituted or substituted with one or more suitable substituents, or where any two ofthe R 15 , R 16 , R 17 and R 18 , taken together with the atoms to which they are bonded, form a heterocycloalkyl group, which is unsubstituted or substituted with one or more suitable substituents, or Z and Z 1 , together with the atoms to which they are bonded, form a cycloalkyl or heterocycloalkyl group, where Z and Z 1 are as defined above. In the compounds ofthe above-described Formulas I-V, R c and R 7 are defined to provide structures where m is 1 and p is 1 -5 (i.e., both A 2 and A 3 are present), m is 0 and p is 0 (i.e, both A 2 and A 3 are absent), m is 0 and p is 1-5 (i.e, A 2 is absent and A 3 is present) and m is 1 and p is 0 (i.e, A 2 is present and A 3 is absent). Accordingly, one of ordinary skill in the are will recognize that when both A 2 and A 3 are present (m is 1 and p is 1-5), the dotted line between A ! and A 2 represents a bond and the dotted line between A 2 , and A 3 represents a bond. Wwhen both A 2 and A 3 are absent (m is 0 and p is 0) A 2 , A 3 and the dotted line between these substituents are not present and the remaining dotted line in the structure between Aj and A 2 represents a hydrogen (e.g., A x is CH 2 or NH). In embodiments of this invention when A 2 is absent and A 3 is present (m is 0 and p is 1-5), the dotted line between Aj and A 2 represents a hydrogen and the dotted line between A 2 and A 3 represents a hydrogen (e.g., Aj is CH 2 or NH and A 3 is CH(R S )(R h ), NH(R), SH, S(O)H, S(O) 2 H, or OH or CH(R 10 )(R U ), NH(R 12 ), SH, S(O)H, S(O) 2 H, or OH); and when A 2 is present and A 3 is absent (m is 1 and p is 0), the dotted line between Aj and A 2 represents a bond and A 2 is C(R g )(R h )(R i ), N(R g )(R i ), S(R*), S(O)(R s ), S(O) 2 (R g ), or 0(R g ) or A 2 is C(R 10 )(R n )(R 12 ), N(R 10 )(R 12 ), S(R 10 ), S(O)(R 10 ), S(O) 2 (R 10 ), or O(R 10 ) or the dotted line between A 2 and A 3 represents a hydrogen and A 2 is CH R^fTl 11 ), NH^ 1 ), SH, S(O)H, S(O) 2 H, or OH or A 2 is CH(R 10 )(R n ), NH(R 12 ), SH, S(O)H, S(O) 2 H, or OH. hi preferred embodiments ofthe compounds of Formula I-V of this invention, m is 1 and p is 1 or 2 or m is 0 and p is 0 or m is 1 and p is 0. More preferably, when m is 1 and p is 1 or 2, A 2 and A 3 are both C(R s )(R h ) or C(R 10 )(R U ), respectively. More preferably, m is 1 and p is 1. In addition to compounds ofthe Formulas I-V, antipicornaviral agents ofthe invention include prodrugs, pharmaceutically active metabolites, and pharmaceutically acceptable salts and solvates of such compounds. DETAILED DESCRIPTION OF INVENTION In accordance with a convention used in the art, <• is used in structural formulas herein to depict the bond that is the point of attachment ofthe moiety or substituent to the core or backbone structure. As used herein, the term "alkyl" represents a straight- or branched-chain saturated or unsaturated hydrocarbon, containing 1 to 10 carbon atoms which may be unsubstituted or substituted by one or more ofthe substituents described below. A C r C 6 alkyl represents an alkyl substituent containing 1 to 6 carbon atoms. Exemplary alkyl substituents include, but are not limited to methyl (Me), ethyl (Et), propyl, isopropyl, butyl, isobutyl, t-butyl, ethenyl, propenyl, butenyl, pentenyl, ethynyl, butynyl, propynyl (propargyl, isopropynyl), pentynyl, hexynyl and the like. The term "lower alkyl" refers to an alkyl group containing from 1 to 4 carbon atoms. "Cycloalkyl" represents a group comprising a non-aromatic monocyclic, bicyclic, or tricyclic hydrocarbon contaimng from 3 to 14 carbon atoms which maybe unsubstituted or substituted by one or more ofthe substituents described below and may be saturated or unsaturated. Exemplary cycloalkyls include monocyclic rings having from 3-7, preferably 3-6, carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl- cyclohexyl, cycloheptyl and the like, that may be fully saturated or partially unsaturated. Illustrative examples of cycloalkyl groups include the following: "Heterocycloalkyl" represents a group comprising a non-aromatic, monovalent monocyclic, bicyclic, or tricyclic radical, which is saturated or partially unsaturated, containing 3 to 18 ring atoms, which includes 1 to 5 heteroatoms selected from nitrogen, oxygen and sulfur, and which may be unsubstituted or substituted by one or more ofthe substituents described below. Illustrative examples of heterocycloalkyl groups include, but are not limited to, azetidinyl, pyrrolidyl, piperidyl, piperazinyl, morpholinyl, tetrahydro-2H-l,4-thiazinyl, tetrahydrofuryl, dihydrofuryl, tetrahydropyranyl, dihydropyranyl, 1,3-dioxolanyl, 1,3-dioxanyl, 1,4-dioxanyl, 1,3-oxathiolanyl, 1,3-oxathianyl, 1,3-dithianyl, azabicyclo[3.2.1]octyl, azabicyclo[3.3.1]nonyl, azabicyclo[4.3.0]nonyl, oxabicyclo[2.2.1]heptyl, 1,5,9-triazacyclododecyl, and the like. Illustrative examples of heterocycloalkyl groups include the following moieties: wherein R is H, alkyl or hydroxyl. "Aryl" represents a group comprising an aromatic, monovalent monocyclic, bicyclic, or tricyclic radical containing from 6 to 18 carbon ring atoms, which may be unsubstituted or substituted by one or more ofthe substituents described below, and to which may be fused one or more cycloalkyl groups, heterocycloalkyl groups or heteroaryl groups, which themselves may be unsubstituted or substituted by one or more suitable substituents. Illustrative examples of aryl groups include the following moieties: "Heteroaryl" represents a group comprising an aromatic monovalent monocyclic, bicyclic, or tricyclic radical, containing 5 to 18 ring atoms, including 1 to 5 heteroatoms selected from nitrogen, oxygen and sulfur, which may be unsubstituted or substituted by one or more ofthe substituents described below. As used herein, the term "heteroaryl" is also intended to encompass the N-oxide derivative (or N-oxide derivatives, if the heteroaryl group contains more than one nitrogen such that more than one N-oxide derivative maybe formed) ofthe nitrogen-containing heteroaryl groups described herein. Illustrative examples of heteroaryl groups include, but are not limited to, thienyl, pyrrolyl, imidazolyl, pyrazolyl, furyl, isothiazolyl, furazanyl, isoxazolyl, thiazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, triazinyl, benzo[b]thienyl, naphtho[2,3-b]tbianthrenyl, isobenzofuranyl, chromenyl, xanthenyl, phenoxathienyl, indolizinyl, isoindolyl, indolyl, indazolyl, purinyl, isoquinolyl, quinolyl, phthalazinyl, naphthyridinyl, quinoxyalinyl, quinzolinyl, benzothiazolyl, benzimidazolyl, tetrahydroquinolinyl, cinnolinyl, pteridinyl, carbazolyl, beta-carbolmyl, phenanthridinyl, acridinyl, perimidinyl, phenanthrolinyl, phenazinyl, isothiazolyl, phenothiazinyl, and phenoxazinyl. Illustrative examples of N-oxide derivatives of heteroaryl groups include, but are not limited to, pyridyl N-oxide, pyrazinyl N-oxide, pyrimidinyl N-oxide, pyridazinyl N-oxide, triazinyl N-oxide, isoquinolyl N-oxide, and quinolyl N-oxide. Further examples of heteroaryl groups include the following moieties: wherein R is H, alkyl or hydroxyl. The term "suitable substituent" represents a substituent that is optionally present on any ofthe above alkyl, aryl, cycloalkyl, heterocycloalkyl or heteroaryl groups, described herein, and is selected from alkyl (except for alkyl) haloalkyl, haloaryl, halocycloalkyl, haloheterocycloalkyl, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, nitro, amino, hydroxamino, cyano, halo, hydroxyl, alkoxy, aUcylenedioxy, aryloxy, cycloalkoxy, heterocycloalkoxy, heteroaryloxy, alkylcarbonyl, alkyloxycarbonyl, alkylcarbonyloxy, arylcarbonyl, arylcarbonyloxy, aryloxycarbonyl, cycloalkylcarbonyl, cycloalkylcarbonyloxy, cycloalkyoxycarbonyl, heteroarylcarbonyl, heteroarylcarbonyloxy, heteroaryloxycarbonyl, heterocycloalkylcarbonyl, heterocycloalkylcarbonyloxy, heterocycloalkyoxycarbonyl, carboxyl, carbamoyl, formyl, keto (oxo), thioketo, sulfo, alkylamino, cycloallcylamino, arylamino, heterocycloalkylamino, heteroarylamino, dialkylamino, alkylaminocarbonyl, cycloalkylaminocarbonyl, arylammocarbonyl, heterocycloalkylaminocarbonyl, heteroarylaminocarbonyl, dialkylaminocarbonyl, alkylaminothiocarbonyl, cycloalkylaminothiocarbonyl, arylaminothiocarbonyl, heterocycloalkylaminothiocarbonyl, heteroarylaminothiocarbonyl, dialkylaminothiocarbonyl, alkylsulfonyl, arylsulfonyl, alkylsulfenyl, arylsulfenyl, alkylcarbonylamino, cycloalkylcarbonylamino, arylcarbonylamino, heterocycloalkylcarbonylamino, heteroarylcarbonylamino, alkylthiocarbonylamino, cycloalkylthiocarbonylamino, arylthiocarbonylamino, heterocycloalkylthiocarbonylamino, heteroarylthiocarbonylamino, alkylsulfonyloxy, arylsulfonyloxy, alkylsulfonylamino, arylsulfonylamino, mercapto, alkylthio, arylthio, and heteroarylthio groups, where any ofthe alkyl, alkylene, aryl, cycloalkyl, heterocycloalkyl, heteroaryl moieties present in the above substituents may be further substituted with one or more substituents selected from nitro, amino, cyano, halo, haloalkyl, haloaryl, hydroxyl, keto, hydroxamino, alkylamino, dialkylamino, mercapto, and unsubstituted alkyl, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, alkoxy, aryloxy, alkylthio or arylthio groups and where any ofthe aryl or heteroaryl moieties may be substituted with aUcylenedioxy. Preferred "suitable substituents" include alkyl, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, halo, hydroxyl, alkoxy, aUcylenedioxy, aryloxy, cycloaUcoxy, heteroaryloxy, and carboxyl. The alkyl, alkylene, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl moieties of any ofthe above substituents maybe optionally substituted by one or more of alkyl (except for alkyl), halo, haloalkyl, aryl or heteroaryl, where the aryl or heteroaryl is unsubstituted or substituted with one or more subsituents, (e.g., haloaryl), independently selected from alkyl, haloalkyl, aUcylenedioxy, nitro, amino, hydroxamino, alkylamino, dialkylamino, halo, hydroxyl, alkoxy, haloalkoxy, aryloxy, mercapto, alkylthio or arylthio groups. The terms "halogen" and "halo" represent chloro, fluoro, bromo or iodo substituents. "Heterocycle" is intended to mean a heteroaryl or heterocycloalkyl group. "Acyl" is intended to mean a -C(O)-R radical, wherein R is an alkyl, cycloalkyl, aryl, heterocycloalkyl or heteroaryl group. "Acyloxy" is intended to mean an -OC(O)-R radical, wherein R is an alkyl, cycloalkyl, aryl, heterocycloalkyl or heteroaryl group. "Thioacyl" is intended to mean a -C(S)-R radical, wherein R is an alkyl, cycloalkyl, aryl, heterocycloalkyl or heteroaryl group. "Sulfonyl" is intended to mean an -SO 2 - biradical. "Sulfenyl" is intended to mean an -SO- biradical. "Sulfo" is intended to mean an -SO 2 H radical. Sulfoxide is intended to mean a -SO 3 ~ radical "Hydroxy" is intended to mean the radical -OH. "Amine" or "amino" is intended to mean the radical -NH 2 . "NUylamino" is intended to mean the radical -ΝH-Pv,, wherein R,. is an alkyl group. "Dialkylamino" is intended to mean the radical -ΝR a R,-, wherein R a and R b are each independently an alkyl group, and is intended to include heterocycloalkyl groups, wherein R^ and R b , taken together, form a heterocyclic ring that includes the amine nitrogen. "Hydroxamino" is intended to mean the radical -N-OH. "Alkoxy" is intended to mean the radical -OR-., wherein R j , is an alkyl group. Exemplary alkoxy groups include methoxy, ethoxy, propoxy, and the like. "Lower alkoxy" groups have alkyl moieties having from 1 to 4 carbons. "AUcylenedioxy" is intended to mean the divalent radical -OR-.O- which is bonded to adjacent atoms on an aryl or heteroaryl moiety (e.g., adjacent atoms on a phenyl or naphthyl ring) , wherein R a is a lower alkyl group. "Alkoxycarbonyl" is intended to mean the radical -C(O)OR., wherein R,. is an alkyl group. "Alkylsulfonyl" is intended to mean the radical -SO^, wherein ^ is an alkyl group. "Alkylaminocarbonyl" is intended to mean the radical -C(O)NHR a , wherein R_. is an alkyl group. "Dialkylaminocarbonyl" is intended to mean the radical -C(O)NR a R b , wherein R a and R b are each independently an alkyl group. "Mercapto" is intended to mean the radical -SH. "Alkylthio" is intended to mean the radical -SR a , wherein R a is an alkyl group. "Carboxyl" is intended to mean the radical -C(O)OH. "Keto" or "oxo" is intended to mean the radical =O. "Thioketo" is intended to mean the radical =S. "Carbamoyl" is intended to mean the radical -C(O)NH 2 . "Cycloalkylalkyi" is intended to mean the radical -alkyl-cycloalkyl, wherein alkyl and cycloalkyl are defined as above, and is exemplified by the bonding arrangement present in the groups -CH 2 -cyclohexane or -CH 2 -cyclohexene. "Arylalkyl" is intended to mean the radical -alkylaryl, wherein alkyl and aryl are defined as above, and is exemplified by the bonding arrangement present in a benzyl group. "Aminocarbonylalkyl" is intended to mean the radical -alkylC(O) NH 2 and is exemplified by the bonding arrangement present in the group -CH 2 CH 2 C(O)NH 2 . "Alkylaminocarbonylalkyl" is intended to mean the radical -alkylC(O)NHR a , wherein a is an alkyl group and is exemplified by the bonding arrangement present in the group -CH 2 CH 2 C(O)NHCH 3 . "Alkylcarbonylaminoalkyl is intended to mean the radical and is exemplified by the bonding arrangement present in the group -CH 2 NHC(O)CH 3 . "Dialkylaminocarbonylalkyl" is intended to mean the radical -aUcylC(O)NR a R b , wherein R^ and R b are each independently an alkyl group. "Aryloxy" is intended to mean the radical -OR c , wherein R c is an aryl group. "Heteroaryloxy" is intended to mean the radical -ORj, wherein R d is a heteroaryl group. "Arylthio" is intended to mean the radical -SR,., wherein R c is an aryl group. "Heteroarylthio" is intended to mean the radical -SR d , wherein R d is a heteroaryl group. The alkyl, cycloalkyl, aryl, heterocycloalkyl and heteroaryl groups and the substituents containing these groups, as defined hereinabove, may be optionally substituted by at least one other substituent. The term "optionally substituted" is intended to expressly indicate that the specified group is unsubstituted or substituted by one or more suitable substituents. Various groups may be unsubstituted or substituted (i.e., they are optionally substituted) as indicated. If the substituents themselves are not compatible with the synthetic methods of this invention, the substituent maybe protected with a suitable protecting group that is stable to the reaction conditions used in these methods. The protecting group may be removed at a suitable point in the reaction sequence ofthe method to provide a desired intermediate or target compound. Suitable protecting groups and the methods for protecting and de-protecting different substituents using such suitable protecting groups are well known to those skilled in the art; examples of which may be found in T. Greene and P. Wuts, Protecting Groups in Chemical Synthesis (3rd ed.), John Wiley & Sons, NY (1999), which is incorporated herein by reference in its entirety, some instances, a substituent may be specifically selected to be reactive under the reaction conditions used in the methods of this invention. Under these circumstances, the reaction conditions convert the selected substituent into another substituent that is either useful in an intermediate compound in the methods of this invention or is a desired substituent in a target compound. Particular embodiments of this invention comprise the compounds of Formulas H and UI, wherein n is 2 or 1, respectively, depicted by the formula: VI wherein: W is CH orN; R a' is an alkyl, cycloalkyl, aryl or heteroaryl group, where the alkyl, cycloalkyl, aryl, and heteroaryl group is unsubstituted or substituted with one or more suitable substituents, provided that R a' is not an amino-substituted alkyl group; R 4 and R 6 are each independently H or a lower alkyl group; R 5 is H or an alkyl group; R 7 is a substituent having the formula: wherein: R 8 and R 9 are each independently H or lower alkyl; p is an integer of from 1 to 5; A j is CH orN; when p is 1, 2, 3, 4, or 5, A 2 is C(R 10 )(R U ), N(R 12 ), S, S(O), S(O) 2 , or O, and when p is 0, A 2 is C(R 10 )(R 1 ] )(R 12 ), N(R 10 )(R 12 ), S(R 10 ), S(O)(R 10 ), S(O) 2 (R 10 ), or O(R 10 ) where each R 10 , R 11 and R 12 is independently H or a lower alkyl group; each A 3 present is independently C(R 10 )(R n ), N(R 12 ), S, S(O), S(O) 2 , or O, where each R 10 , R π and R 12 is independently H or a lower alkyl group; when p is 1, 2, 3, 4, or 5, A 4 is N(R 13 ), C(R 10 )(R U ), or O, and when p is 0, A 4 is N(R 13 )(R 14 ), C(R 10 )(R n )(R 12 ), and O(R 14 ), where each R 10 , R" and R 12 is independently H or a lower alkyl group, each R 13 is H or an alkyl, aryl, or acyl group, and each R 14 is H or an alkyl or aryl group; provided that no more than two heteroatoms occur consecutively in the above-depicted ring formed by A l5 (A 2 ) m , (A 3 ) p , A 4 , and C=O, where each dotted line in the ring depicts a single bond when A 2 is present and a hydrogen atom when A 2 is absent; and Z and Z 1 are each independently H, F, an alkyl, cycloaUcyl, heterocycloalkyl, aryl or heteroaryl group, where the alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl group is unsubstituted or substituted with one or more suitable substituents, -C(O)R 15 , -CO 2 R 15 , -CN, -C(O)NR 15 R 16 , -C(O)NR 15 OR 16 , -C(S)R 15 , -C(S)OR 15 , -C(S)NR 15 R 16 , -C(=NR 15 )R 16 , -C(=NR 15 )OR 16 , -NO 2 , -SOR 16 , -SO 2 R 15 , -SO 2 NR 15 R 16 , -SO 2 (NR 15 )(OR 16 ), -SONR 15 , -SO 3 R 15 , -PO(OR 15 ) 2 , -PO(OR 15 )(OR 16 ) ; -PO(NR 15 R 16 )(OR 17 ) ) -PO(NR 15 R 16 )(NR 17 R 18 ), -C(O)NR 15 NR 16 R 17 , -C(S)NR 15 NR 16 R 17 , where R 15 , R 16 , R 17 and R 18 are each independently H or an alkyl, cycloalkyl, aryl, heterocycloalkyl, acyl or thioacyl group, where the alkyl, cycloaUcyl, aryl, heterocycloalkyl, acyl or thioacyl group is unsubstituted or substituted with one or more suitable substituents, or where any two ofthe R 15 , R 16 , R 17 and R 18 , taken together with the atoms to which they are bonded, form a heterocycloalkyl group, which is unsubstituted or substituted with one or more suitable substituents, or Z and Z 1 , together with the atoms to which they are bonded, form a cycloaUcyl or heterocycloalkyl group, where Z and Z 1 are as defined above (except for moieties that cannot form the cycloalkyl or heterocycloalkyl group); or a prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate thereof of said compound. More specifically, preferred embodiments of Formula VI of this invention comprise the compounds depicted by the formula: vπ wherein R ' , R 4 , R 5 , R 6 , R 7 , Z and Z 1 are as defined above; and the compounds depicted by the formula: vm wherein R a ', R 4 , R 5 , R 6 , R 7 , Z and Z 1 are as defined above. In particular, this invention comprises the compounds depicted by the formula: LX wherein: R 1 is H, halo or an alkoxy, alkyl, aryl, cycloaUcyl, heterocycloalkyl or heteroaryl group, where the alkoxy, alkyl, aryl, cycloalkyl, heterocycloalkyl, or heteroaryl group is unsubstituted or substituted with one or more suitable substituents; R 2 and R 3 are each independently H, halo or an alkoxy or lower alkyl group, where the alkoxy or lower alkyl group is unsubstituted or substituted with one or more suitable substituents; or R 1 together with R 2 form a cycloalkyl, heterocycloalkyl, aryl or heteroaryl ring, where the cycloaUcyl, heterocycloalkyl, aryl or heteroaryl ring is unsubstituted or substituted with one or more suitable substituents; R 4 and R 6 are each independently H or a lower alkyl group, unsubstituted or substituted with one or more suitable substituents; R s is H or an alkyl group, unsubstituted or substituted with one or more suitable substituents; R 7 is a moiety having the formula: wherein: R 8 and R 9 are each each independently H or a lower alkyl group; m is O or l; p is an integer of from 0 to 5; A^s CH orN; when p is 1, 2, 3, 4, or 5, A 2 is C(R 10 )(R n ), N(R 12 ), S, S(O), S(O) 2 , or O, and when p is 0, A 2 is C(R 10 )(R U )(R 12 ), N(R 10 )(R 12 ), S(R 10 ), S(O)(R 10 ), S(O) 2 (R 10 ), or O(R !0 ) where each R 10 , R π and R 12 is independently H or a lower alkyl group; each A 3 present is independently C(R 10 )(R n ), N(R 12 ), S, S(O), S(O) 2 , or O, where each R 10 , R 11 and R 12 is independently H or a lower alkyl group; when p is 1, 2, 3, 4, or 5, A 4 is N(R 13 ), C(R 10 )(R π ), or O, and when p is 0, A 4 is N(R 13 )(R 14 ), C(R 10 )(R n )(R 12 ), and O(R 14 ), where eachR 10 , R 11 andR 12 is independently H or a lower alkyl group, each R 13 is H or an alkyl, aryl, or acyl group, and each R 14 is H or an alkyl or aryl group; provided that no more than two heteroatoms occur consecutively in the above-depicted ring formed by A , (A 2 ) m , (A 3 ) p , A 4 , and C=O, where each dotted line in the ring depicts a single bond when A 2 is present and a hydrogen atom when A 2 is absent; and Z and Z 1 are each independently H, F, an alkyl, cycloaUcyl, heterocycloalkyl, aryl or heteroaryl group, where the alkyl, cycloaUcyl, heterocycloalkyl, aryl or heteroaryl group is unsubstituted or substituted with one or more suitable substituents, -C(O)R 15 , -CO 2 R 15 , -CN, -C(O)NR ,5 R 16 , -C(O)NR 15 OR 16 , -C(S)R 15 , -C(S)OR 15 , -C(S)NR 15 R 16 , -C(=NR 15 )R 16 , -C(=NR 15 )OR 16 , -NO 2 , -SOR 16 , -SO 2 R 15 , -SO 2 NR 15 R 16 , -SO 2 (NR 15 )(OR 16 ), -SONR 15 , -SO 3 R 15 , -PO(OR 15 ) 2 , -PO(OR 15 )(OR 16 ) ; -PO(NR 15 R 16 )(OR 17 ) ; -PO(NR 15 R 16 )(NR 17 R 18 ), -C(O)NR 15 NR I6 R 17 , -C(S)NR 15 NR 16 R 17 , where R 15 , R 16 , R 17 and R 18 are each independently H or an alkyl, cycloaUcyl, aryl, heterocycloalkyl, acyl or thioacyl group, where the alkyl, cycloalkyl, aryl, heterocycloalkyl, acyl or thioacyl group is unsubstituted or substituted with one or more suitable substituents, or where any two ofthe R 15 , R 16 , R 17 and R 18 , taken together with the atoms to which they are bonded, form a heterocycloalkyl group, which is unsubstituted or substituted with one or more suitable substituents, or Z and Z 1 , together with the atoms to which they are bonded, form a cycloalkyl or heterocycloalkyl group, where Z and Z 1 are as defined above (except for moieties that cannot form the cycloaUcyl or heterocycloalkyl group); or a prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate of said compound. Another embodiment of this invention comprises the compounds depicted by the formula: X wherein: R 1 is H, halo or an alkoxy, alkyl, aryl, cycloaUcyl, heterocycloalkyl, or heteroaryl group, where the alkoxy, alkyl, aryl, cycloaUcyl, heterocycloalkyl, or heteroaryl group is unsubstituted or substituted with one or more suitable substituents; R 2 and R 3 are each independently H, halo or an alkoxy or lower alkyl group, where the alkoxy or lower alkyl group is unsubstituted or substituted with one or more suitable substituents; or R 1 together with R 2 form a cycloaUcyl, heterocycloalkyl, aryl or heteroaryl ring, where the cycloaUcyl, heterocycloalkyl, aryl or heteroaryl ring is unsubstituted or substituted with one or more suitable substituents; R 4 and R 6 are each independently H or lower alkyl, unsubstituted or substituted with one or more suitable substituents; R 5 is H or an alkyl group, unsubstituted or substituted with one or more suitable substituents; R 7 is a moiety having the formula: wherein: R 8 and R 9 are each independently H or a lower alkyl group; m is 0 or 1, provided that when m is 0 and R 1 together with R 2 form an aryl ring, the aryl ring is unsubstituted (e.g., R 1 together with R 2 and the pyrrole to which they are bound do not form a substituted indole); p is an integer of from 0 to 5; when p is 1, 2, 3, 4, or 5, A 2 is C(R 10 )(R n ), N(R 12 ), S, S(O), S(O) 2 , or O, and when p is 0, A 2 is C(R 10 )(R π )(R 12 ), N(R 10 )(R 12 ), S(R 10 ), S(O)(R ]0 ), S(O) 2 (R 10 ), or O(R 10 ) where each R 10 , R 11 and R 12 is independently H or a lower alkyl group; each A 3 present is independently C(R 10 )(R I l ), N(R 12 ), S, S(O), S(O) 2 , or O, where each R 10 , R 11 and R 12 is independently H or a lower alkyl group; when p is 1, 2, 3, 4, or 5, A 4 is N(R 13 ), C(R 10 )(R π ), or O, and when p is 0, A 4 is N(R 13 )(R 14 ), C(R 10 )(R n )(R 12 ), and O(R 14 ), where each R 10 , R π and R 12 is independently H or a lower alkyl group, each R 13 is H or an alkyl, aryl, or acyl group, and each R 14 is H or an alkyl or aryl group; provided that no more than two heteroatoms occur consecutively in the above-depicted ring formed by A l5 (A 2 ) m , (A 3 ) p , A 4 , and C=O, where each dotted line in the ring depicts a single bond when A 2 is present and a hydrogen atom when A 2 is absent; and Z and Z 1 are each independently H, F, an alkyl, cycloaUcyl, heterocycloalkyl, aryl or heteroaryl group, where the alkyl, cycloaUcyl, heterocycloalkyl, aryl or heteroaryl group is unsubstituted or substituted with one or more suitable substituents, -C(O)R 15 , -CO 2 R 15 , -CN, -C(O)NR 15 R 16 , -C(O)NR 15 OR 16 , -C(S)R 15 , -C(S)OR 15 , -C(S)NR 15 R 16 , -C(=NR 15 )R 16 , -C(=NR 15 )OR 16 , -NO 2 , -SOR 16 , -SO 2 R 15 , -SO 2 NR 15 R 16 , -SO 2 (NR 15 )(OR 16 ), -SONR 15 , -SO 3 R 15 , -PO(OR 15 ) 2 , -PO(OR 15 )(OR 16 ) > -PO(NR 15 R 16 )(OR 17 ) , -PO(NR 15 R 16 )(NR 17 R 18 ), -C(O)NR 15 NR 16 R 17 , -C(S)NR 15 NR 16 R 17 , where R 15 , R 16 , R 17 and R 18 are each independently H or an alkyl, cycloaUcyl, aryl, heterocycloalkyl, acyl or thioacyl group, where the alkyl, cycloaUcyl, aryl, heterocycloalkyl, acyl or thioacyl group is unsubstituted or substituted with one or more suitable substituents, or where any two ofthe R 15 , R 16 , R 17 and R 18 , taken together with the atoms to which they are bonded, form a heterocycloalkyl group, which is unsubstituted or substituted with one or more suitable substituents, or Z and Z 1 , together with the atoms to which they are bonded, form a cycloalkyl or heterocycloalkyl group, where Z and Z 1 are as defined above (except for moieties that cannot form the cycloaUcyl or heterocycloalkyl group); or a prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate of said compound. h another embodiment ofthe compounds ofthe above formulas, A, is CH orN; A 2 is C(R 10 )(R U ), N(R 12 ), S, S(O), S(O) 2 , or O, where each R 10 , R u and R 12 is independently H or a lower alkyl group; each A 3 present is independently C(R 10 )(R U ), N(R 12 ), S, S(O), S(O) 2 , or O, where each R 10 , R 11 and R 12 is independently H or a lower alkyl group; when p is 1, 2, 3, 4, or 5, A 4 is N(R 13 ), C(R 10 )(R n ), or O, and when p is 0, A 4 is N(R 13 )(R 14 ), C(R 10 )(R U )(R 12 ), and O(R 14 ), where each R 10 , R 11 and R 12 is independently H or a lower alkyl group, each R 13 is H or an alkyl, aryl, or acyl group, and each R 14 is H or an alkyl or aryl group; provided that no more than two heteroatoms occur consecutively in the above-depicted ring formed by A,, (A 2 ) m , (A 3 ) p , A 4 , and C=O, where each dotted line in the ring depicts a single bond when A 2 is present and a hydrogen atom when A 2 is absent; and Z and Z 1 are each independently H, F, an alkyl, cycloaUcyl, heterocycloalkyl, aryl or heteroaryl group, where the alkyl, aryl, cycloaUcyl, heterocycloalkyl, aryl or heteroaryl group is unsubstituted or substituted with one or more suitable substituents, -C(O)R 15 , -CO 2 R 15 , -CN, -C(O)NR 15 R 16 , -C(O)NR ,5 OR 16 , -C(S)R 15 , -C(S)NR 15 R 16 , -NO 2 , -SOR 16 , -SO 2 R 15 , -SO 2 NR 15 R 16 , -SO 2 (NR ls )(OR 16 ), -SONR 15 , -SO 3 R 15 , -PO(OR 15 ) 2 , -PO(OR 15 )(OR 16 ) , -PO(NR 15 R 16 )(OR 17 ) , -PO(NR 15 R 16 )(NR 17 R 18 ), -C(O)NR 15 NR 16 R 17 , -C(S)NR 15 NR 16 R 17 , where R 15 , R 16 , R 17 and R 18 are each independently H or an alkyl, cycloaUcyl, aryl, heterocycloalkyl, acyl or thioacyl group, where the alkyl, aryl, cycloalkyl, aryl, heterocycloalkyl, acyl or thioacyl group is unsubstituted or substituted with one or more suitable substituents, or where any two ofthe R 15 , R 16 , R 17 and R 18 , taken together with the atoms to which they are bonded, form a heterocycloalkyl group, which is unsubstituted or substituted with one or more suitable substituents, or Z and Z 1 , together with the atoms to which they are bonded, form a cycloaUcyl or heterocycloalkyl group, where Z and Z 1 are as defined above. Preferably, in the compounds of Formulas J_X and X, R 1 maybe selected from H and a lower alkyl, phenyl, naphthyl, pyridyl, quinoyl, isoquinoyl or isoxazoyl group, where the lower alkyl, phenyl, naphthyl, pyridyl, quinoyl, isoquinoyl or isoxazoyl group is unsubstituted or substituted with one or more substituents selected from alkyl (but not as a substituent for alkyl), hydroxy, halo, haloalkyl, alkoxy, haloalkoxy and aUcylenedioxy moiety. Exemplary R 1 groups include, but are not limited to H, phenyl, α-naphthyl, β-naphthyl, 2-chlorophenyl, 2-α,α,α-trifluoromethylphenyl, 3-chloro-6- methoxyphenyl, 2,3-dichlorophenyl, 4-isoquinoyl, 3-iso-propylphenyl, 2,5-dimethoxyphenyl, 2-methoxyphenyl, 2-methylphenyl (o-tolyl), 2-bromophenyl, 3-pyridyl, 4-pyridyl, 3-methyl-isoxazol-5-yl, 3,3,3-trifluoroprop-l-yl, and 2,3-benzo[d]dioxolyl. Preferably, in the compounds of Formulas LX and X, R 2 and R 3 may be each independently selected from H, halo, alkoxy, unsubstituted lower alkyl, haloalkyl, and lower alkoxyalkyl. R 4 and R 6 may be each independently selected from H, unsubstituted lower alkyl, haloalkyl and lower alkoxyalkyl. Yet another preferred embodiment of this invention comprises the compounds depicted by the formula: XI wherein: each R z is H or a suitable substituent and n z is an integer from 1 to 4; R 7 is a moiety having the formula: wherein: R 8 and R 9 are each independently H or a lower alkyl group; p is an integer of from 1 to 5; when p is 1, 2, 3, 4, or 5, A 2 is C(R 10 )(R n ), N(R 12 ), S, S(O), S(O) 2 , or O, and when p is 0, A 2 is C^ 10 )^ 1 l )(R 12 ), N(R I0 )(R 12 ), S(R 10 ), S(O)(R 10 ), S(O) 2 (R 10 ), or O(R 10 ) where each R 10 , R 11 and R 12 is independently H or a lower alkyl group; each A 3 present is independently C(R 10 )(R π ), N(R 12 ), S, S(O), S(O) 2 , or O, where each R 10 , R 11 and R 12 is independently H or a lower alkyl group; A 4 is N(R 13 ), C(R 10 )(R π ), or O, where R 10 and R n are each independently H or a lower alkyl group, and R 13 is H or an alkyl, aryl or acyl group; provided that no more than two heteroatoms occur consecutively in the above-depicted ring formed by A,, (A 2 ) m , (A 3 ) p , A 4 , and C=O; and each R 3 , R 4 , R 5 , R 6 , Z and Z 1 are as defined above. Preferably, in the compounds of Formula XI, each R z is independently selected from H, halo, alkoxy, unsubstituted lower alkyl, haloalkyl, and lower alkoxyalkyl. R 3 may be independently selected from H, halo, alkoxy, unsubstituted lower alkyl, haloalkyl and lower alkoxyalkyl and R 4 and R 6 may be each independently selected from H, unsubstituted lower alkyl, haloalkyl and lower alkoxyalkyl. Another preferred embodiment of this invention comprise the compounds of Formula JV, wherein n is 1, depicted by the formula: xπ wherein: R a' is an alkyl, aryl, cycloaUcyl, heterocycloalkyl or heteroaryl, where the alkyl, aryl, cycloalkyl, heterocycloalkyl, or heteroaryl group is unsubstituted or substituted with one or more suitable substituents; R 5 is H or an alkyl group, unsubstituted or substituted with one or more suitable substituents,; each R 6 is independently H or a lower alkyl group, unsubstituted or substituted with one or more suitable substituents,; R 7 is a moiety having the formula: wherein: R 8 and R 9 are each independently H or a lower alkyl group; m is O or 1; p is an integer of from 0 to 5; A j is CH orN; when p is 1, 2, 3, 4, or 5, A 2 is C(R 10 )(R n ), N(R 12 ), S, S(O), S(O) 2 , or O, and when p is 0, A 2 is C(R 10 )(R n )(R 12 ), N(R 10 )(R 12 ), S(R 10 ), S(O)(R 10 ), S(O) 2 (R 10 ), or O(R 10 ) where each R 10 , R" and R 12 is independently H or a lower alkyl group; each A 3 present is independently C(R I0 )(R n ), N(R 12 ), S, S(O), S(O) 2 , or O, where each R 10 , R 11 and R 12 is independently H or a lower alkyl group; when p is 1, 2, 3, 4, or 5, A 4 is N(R 13 ), C(R 10 )(R n ), or O, and when p is 0, A 4 is N(R 13 )(R 14 ), C(R 10 )(R n )(R 12 ), and O(R 14 ), where each R 10 , R 11 and R 12 is independently H or a lower alkyl group, each R 13 is H or an alkyl, aryl, or acyl group, and each R 14 is H or an alkyl or aryl group; provided that no more than two heteroatoms occur consecutively in the above-depicted ring formed by A,, (A 2 ) m , (A 3 ) p , A 4 , and C=O, where each dotted line in the ring depicts a single bond when A 2 is present and a hydrogen atom when A 2 is absent; and Z and Z 1 are each independently H, F, an alkyl, cycloaUcyl, heterocycloalkyl, aryl or heteroaryl group, where the alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl group is unsubstituted or substituted with one or more suitable substituents, -C(O)R 15 , -CO 2 R 15 , -CN, -C(O)NR 15 R 16 , -C(O)NR 15 OR 16 , -C(S)R 15 , -C(S)OR ls , -C(S)NR 15 R 16 , -C(=NR 15 )R 16 , -C(=NR 15 )OR 16 , -NO 2 , -SOR 16 , -SO 2 R 15 , -SO 2 NR 15 R 16 , -SO 2 (NR 15 )(OR 16 ), -SONR 15 , -SO 3 R 15 , -PO(OR 15 ) 2 , -PO(OR 15 )(OR 16 ) ( -PO(NR 15 R 16 )(OR 17 ) ; -PO(NR 15 R 16 )(NR I7 R 18 ), -C(O)NR 15 NR 16 R 17 , -C(S)NR 15 NR 16 R 17 , where R 15 , R 16 , R 17 and R 18 are each independently H or an alkyl, cycloaUcyl, aryl, heterocycloalkyl, acyl or thioacyl group, where the alkyl, cycloaUcyl, aryl, heterocycloalkyl, acyl or thioacyl group is unsubstituted or substituted with one or more suitable substituents, or where any two ofthe R 15 , R 16 , R 17 and R 18 , taken together with the atoms to which they are bonded, form a heterocycloalkyl group, which is unsubstituted or substituted with one or more suitable substituents, or Z and Z 1 , together with the atoms to which they are bonded, form a cycloalkyl or heterocycloalkyl group, where Z and Z 1 are as defined above (except for moieties that cannot form the cycloalkyl or heterocycloalkyl group); or a prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate of said compound. In another embodiment ofthe compounds ofthe above formulas, Z and Z 1 are each independently H, F, an alkyl, cycloaUcyl, heterocycloalkyl, aryl or heteroaryl group, where the alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl group is unsubstituted or substituted with one or more suitable substituents, -C(O)R 15 , -CO 2 R 15 , -CN, -C(O)NR I5 R 16 , -C(O)NR 15 OR 16 , -C(S)R 15 , -C(S)NR 15 R 16 , -NO 2 , -SOR 16 , -SO 2 R 15 , -SO 2 NR 15 R 16 , -SO 2 (NR 15 )(OR 16 ), -SONR 15 , -SO 3 R 15 , -PO(OR 15 ) 2 , -PO(OR I5 )(OR 16 ) > -PO(NR 15 R 16 )(OR I7 ) ι -PO(NR I5 R I6 )(NR 17 R i8 ), -C(O)NR I5 NR 16 R 17 , -C(S)NR 15 NR 16 R 17 , where R 15 , R 16 , R 17 and R 18 are independently H or an alkyl, cycloaUcyl, aryl, heterocycloalkyl, acyl or thioacyl group, where the alkyl, cycloaUcyl, aryl, heterocycloalkyl, acyl or thioacyl group is unsubstituted or substituted with one or more suitable substituents, or where any two ofthe R 15 , R 16 , R 17 and R 18 , taken together with the atoms to which they are bonded, form a heterocycloalkyl group, which is unsubstituted or substituted with one or more suitable substituents, or Z and Z 1 , together with the atoms to which they are bonded, form a cycloaUcyl or heterocycloalkyl group, where Z and Z 1 are as defined above. Preferably, in the compounds of Formula XH, R a' may be selected from H, lower alkyl, phenyl, naphthyl, pyridyl, quinoyl, isoquinoyl and isoxazoyl, each of which may be substituted by alkyl (but not as a substituent for alkyl), hydroxy, halo, haloalkyl, alkoxy, haloaUcoxy and aUcylenedioxy. Each R 6 may be independently selected from H, unsubstituted lower alkyl, haloalkyl and loweralkoxyalkyl. If an inventive compound is a base, a desired salt may be prepared by any suitable method known in the art, including treatment ofthe free base with an inorganic acid, such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like, or with an organic acid, such as acetic acid, maleic acid, succinic acid, mandelic acid, fumaric acid, malonic acid, pyruvic acid, oxalic acid, glycolic acid, salicylic acid, pyranosidyl acid, such as glucuronic acid or galacturonic acid, alpha-hydroxy acid, such as citric acid or tartaric acid, amino acid, such as aspartic acid or glutamic acid, aromatic acid, such as benzoic acid or cinnamic acid, sulfonic acid, such as p-toluenesulfonic acid or ethanesulfonic acid, or the like. If an inventive compound is an acid, a desired salt may be prepared by any suitable method known to the art, including treatment ofthe free acid with an inorganic or organic base, such as an amine (primary, secondary, or tertiary); an alkali metal or alkaline earth metal hydroxide; or the like. Illustrative examples of suitable salts include organic salts derived from amino acids such as glycine and arginine; ammonia; primary, secondary, and tertiary amines; and cyclic amines, such as piperidine, morpholine, and piperazine; as well as inorganic salts derived from sodium, calcium, potassium, magnesium, manganese, iron, copper, zinc, aluminum, and lithium. All compounds of this invention contain at least one chiral center and may exist as single stereoisomers (e.g., single enantiomers or diastereomers), any mixture of stereosisomers (e.g., any mixture of enantiomers or diastereomers) or racemic mixtures thereof. All such single stereoisomers, mixtures and racemates are intended to be encompassed within the broad scope ofthe present invention. Where the stereochemistry of the chiral carbons present in the chemical structures illustrated herein is not specified, the chemical structure is intended to encompass compounds containing either stereoisomer of each chiral carbon. When used describe a particular compound, the term "optically pure" is used herein to indicate that the compound is substantially enantiomerically or diastereomerically pure. Compounds that are substantially enatiomerically pure contain at least 90% of a single isomer and preferably contain at least 95% of a single isomer. Compounds that are substantially diastereomerically pure contain at least 90% of a single isomer of each chiral carbon center present in the diastereomer, and preferably contain at least 95% of a single isomer of each chiral carbon. More preferably, when an optically active compound is desired, it contains at least 97.5% of a single isomer and, most preferably, at least 99% ofthe single isomer. Compounds identified herein as single stereoisomers are meant to describe compounds that are present in a form that contains at least 90% of a single isomer. The term "racemic" or "racemic mixture" refers to a mixture of equal amounts of enantiomeric compounds, which encompasses mixtures of enantiomers and mixtures of enantiomeric diastereomers. The compounds of this invention may be obtained in stereochemically (e.g., enantiomerically or diastereomerically ) pure or substantially stereochemically pure form. Such compounds may be obtained synthetically, according to the procedures described herein using optically pure or substantially optically pure materials. Alternatively, these compounds may be obtained by resolution/separation of a mixture of stereoisomers, including racemic mixtures, using conventional procedures. Exemplary methods that may be useful for the resolution/separation of stereoisomeric mixtures include chromatography and crystallization/re-crystallization. Other useful methods may be found in "Enantiomers, Racemates, and Resolutions," J. Jacques et al., 1981, John Wiley and Sons, New York, NY. Preferred stereoisomers ofthe compounds of this invention are described herein. In especially preferred embodiments of Formulas V, VI, VH, VHJ, IX, X, XI and XJJ, R 5 (or R x or R y in Formulas E, HJ and VI) is H or an unsubstituted alkyl group or an optionally substituted lower alkyl group, where these groups are comprised of a straight- or branched-chain saturated hydrocarbon group, a straight- or branched-chain substituted saturated hydrocarbon group, or group comprised of a straight- or branched-chain saturated hydrocarbon moiety and an unsaturated hydrocarbon moiety. When R 5 or R x /R y is a substituted alkyl group, the point of attachment of R 5 or R x R y is via a saturated hydrocarbon moiety. When R 5 or R x /R y is a substituted saturated hydrocarbon group, the saturated hydrocarbon group may be optionally substituted with a cycloaUcyl group, a heterocycloalkyl group, an aryl group, a heteroaryl group, an alkoxy group, an aryloxy group, an alkylthio group, an arylthio group, where each alkyl, cycloalkyl, aryl, heterocycloalkyl or heteroaryl moiety thereof maybe optionally substituted. When R 5 or R x /R y is comprised of a saturated hydrocarbon moiety and an unsaturated hydrocarbon moiety, the saturated hydrocarbon moiety may be bound to an unsaturated hydrocarbon moiety containing one or more double-bonds or triple-bonds, the terminal positions of which may be substituted by the substituents described above, or may contain additional straight- or branched-chain saturated hydrocarbon moieties. Preferably, the unsaturated hydrocarbon moiety contains one double-bond or one triple-bond, the terminal position(s) of which may optionally contain a straight- or branched-chain saturated hydrocarbon moiety. Preferably, if the unsaturated hydrocarbon moiety contains a double-bond, both terminal positions ofthe double bond contain a straight- or branched-chain saturated hydrocarbon moiety. In especially preferred embodiments, R 5 or R x /R y is H or a lower alkyl, arylalkyl, heteroarylalkyl, cycloaUcylaUcyl group, or a group comprised of a straight-chain saturated hydrocarbon moiety and an unsaturated hydrocarbon moiety, where the alkyl, arylalkyl, heteroarylalkyl, cycloaUcylaUcyl group is unsubstituted or substituted with one or more suitable substituents. Preferably, R 5 or R x /R y is H or substituted or unsubstituted methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, 2-propen-l-yl, 2-propen-2-yl, 2-propyn-l-yl, 3-methyl-3-buten-l-yl, -methylcyclohexyl, substituted or unsubstituted -methylthienyl or substituted or unsubstituted benzyl, where the methyl, ethyl, propyl, propenyl, butenyl or cyclohexyl moiety thereof is optionally substituted with one or more substituents independently selected from lower alkoxy, hydroxy, amino, aUcylamino or diaUcylamino and halogen, the phenyl moiety ofthe substituted benzyl is substituted by one or more substituents independently selected from lower alkyl, lower alkoxy, hydroxy, amino, aUcylamino or dialkylamino and halogen and the thienyl moiety ofthe substituted -methylthienyl is substituted by one or more substituents independently selected from lower alkyl, lower alkoxy, hydroxy, amino, alkylamino, diaUcylamino and halogen. When R 5 or R7R y is substituted methyl, the methyl (methylene) moiety may be substituted with an alkoxy group, an aryloxy group, an alkylthio group or an arylthio group. Most preferably, R 5 or R7R y is H, ethyl, 2-propyn-l-yl, -methylcyclohexyl, or substituted or unsubstituted benzyl, where the phenyl moiety of the substituted benzyl is substituted by one or more substituents independently selected from lower alkyl, lower alkoxy and halogen. In the especially preferred embodiments of Formulas V, VI, VH, VIH, XI, X XI and XH, R 5 (or R x or R y in Formulas H, JJJ and VI) is selected from H and: CH-, VY ' CH 3 CH 3 CH 3 V ^ S ' wherein R' may be H or alkyl and each R" may be H or independently selected from lower alkyl, lower alkoxy, hydroxy, amino, aUcylamino or diaUcylamino, and halogen. Preferred are > — ( — F In especially preferred embodiments of Formulas V, VI, VH, VHI, DC, X, XI and XH, R 7 (or R c in Formulas I, H, HI and VI) is selected from -CH 2 CH 2 C(O)NH 2 ; -CH 2 CH 2 C(O)NH-aUcyl; -CH 2 NHC(O)CH 3 ; and , where n is 1 or 2. More preferably, R 7 is Preferably, in each ofthe formulas described herein, Z and Z 1 are each independently H, alkyl, where the alkyl is unsubstituted or substituted with one or more suitable substituents, -CO 2 R 15 (in Formulas V to XH) or -CO^ 1 (in Formulas I to VI), where R 1 and R 15 are as defined above, or Z and 7), taken together with the atom to which they are attached, form a heterocycloalkyl group, as defined above, which may be optionally substituted. In one useful embodiment ofthe compounds of this invention, Z and/or Z 1 maybe -C(S)OR n or -C(S)OR 19 , where R n and R 19 are as defined above. Such compounds may be prepared using procedures described in K. Hartke, et al., Leibigs Ann. Chem., 321-330 (1989) and K. Hartke, et al., Synthesis, 960-961 (1985). More preferably, the heterocycloalkyl group may optionally contain O, N, S and/or P and may be substituted by one or more of oxo (keto) or thioketo. In another preferred embodiment of this invention, Z and Z 1 are each independently selected from H, lower alkyl which is unsubstituted or substituted with one or more suitable substituents, -CO 2 H, -CO 2 -alkyl and -CO 2 -cycloalkyl, or taken together with the atom to which they are attached form a heterocycloalkyl group , which is optionally substituted with one or more of keto or thioketo. In other preferred embodiments of this invention, Z and Z 1 are not both H. Most preferably, Z 1 is H or lower alkyl and Z is a -CO 2 H, -CO 2 -alkyl, -CO 2 -alkylaryl, -CO 2 -aUcylheteroaryl, -CO 2 -cycloaUcyl group, where the lower alkyl, -alkyl, -cycloalkyl, -alkylaryl and -alkylheteroaryl moieties thereof are unsubstituted or substituted with one or more suitable substituents, or Z 1 and Z taken together with the atom to which they are attached form a heterocycloalkyl group, which may be optionally substituted. Exemplary Z groups include, but are not limited to: substituted and unsubstituted -CO 2 -aUcyl groups, which include straight- and branched-chain aUcyl groups such as ethoxycarbonyl, t-butoxycarbonyl, isopropoxycarbonyl and (2,2-dimethylpropyl)-oxycarbonyl, where the ethoxy, t-butoxy, isopropoxy, and (2,2-dimethylpropyl)-oxy moieties thereof are unsubstituted or substituted with one or more suitable substituents; and include substituted and unsubstituted straight and branched-chain arylalkyl and heteroarylalkyl groups, such as benzyloxycarbonyl and pyridylmethyleneoxycarbonyl, where the benzyl and pyridylmethylene moieties thereof are unsubstituted or substituted with one or more suitable substituents; and include substituted and unsubstituted -CO 2 -cycloalkyl groups such as cyclobutyloxycarbonyl, cyclopentyloxycarbonyl, cyclohexyloxycarbonyl and cycloheptyloxycarbonyl groups, where the cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl moieties thereof are unsubstituted or substituted with one or more suitable substituents, or Z 1 and Z taken together with the atom to which they are attached form Formulas V to XH , in Formulas I to VI). In another embodiment of this invention, 7) is H and Z is -CO 2 CH 2 CH 3 , -CO 2 (CH(CH 3 ) 2 ), -CO 2 (C(CH 3 ) 3 ), -CO 2 CH 2 (C(CH 3 ) 3 ), -CO 2 (cyclo-C 5 H 9 ) or Z 1 and Z taken together with the atom to which they are attached form In yet another embodiment of this invention, Z 1 is H and Z is selected from ethoxycarbonyl, t-butoxycarbonyl, isopropoxycarbonyl, (2,2-dimethylpropyl)- oxycarbonyl, benzyloxycarbonyl, pyridylmethyleneoxycarbonyl, cyclobutyloxycarbonyl, cyclopentyloxycarbonyl, cyclohexyloxycarbonyl and cycloheptyloxycarbonyl, or Z 1 and Z taken together with the atom to which they are attached form In the compounds of each ofthe above-described Formulas, R c and R 7 are defined to provide structures where m is 1 and p is 1 -5 (i.e., both A 2 and A 3 are present), m is 0 and p is 0 (i.e, both A 2 and A 3 are absent), m is 0 and p is 1-5 (i.e, A 2 is absent and A 3 is present) and m is 1 and p is 0 (i.e, A 2 is present and A 3 is absent). Accordingly, one of ordinary skill in the are will recognize that when both A 2 and A 3 are present (m is 1 and p is 1-5), the dotted line between A ! and A 2 represents a bond and the dotted line between A 2 and A 3 represents a bond and when both A 2 and A 3 are absent (m is 0 and p is 0); A 2 , A 3 and the dotted line between these substituents are not present), the remaining dotted line in the stracture between A t and A 2 represents a hydrogen (e.g., A x is CH 2 or NH). In embodiments of this invention when A 2 is absent and A 3 is present (m is 0 and p is 1-5), the dotted line between A x and A 2 represents a hydrogen and the dotted line between A 2 and A 3 represents a hydrogen (e.g., Aj is CH 2 or NH and A 3 is CH(R £ )(R h ), NH(R), SH, S(O)H, S(O) 2 H, or OH or CH(R 10 )(R n ), NH(R 12 ), SH, S(O)H, S(O) 2 H, or OH); and when A 2 is present and A 3 is • absent (m is 1 and p is 0), the dotted line between A λ and A 2 represents a bond and A 2 is C(R g )(R h )(R i ), N^ R 1 ), S(R S ), S(0)(R ), S(O) 2 (R g ), or €>( *) or A 2 is C(R 10 )(R U )(R 12 ), N(R 10 )(R 12 ), S(R 10 ), S(O)(R 10 ), S(O) 2 (R 10 ), or O(R 10 ) or the dotted line between A 2 and A 3 represents a hydrogen and A 2 is CHOR^ R 11 ), NHOR- 1 ), SH, S(O)H, S(O) 2 H, or OH or A 2 is CH(R 10 )(R n ), NH(R 12 ), SH, S(O)H, S(O) 2 H, or OH. In preferred embodiments ofthe compounds of each ofthe above-described Formulas, m is 1 and p is 1 or 2 or m is 0 and p is 0 or m is 1 and p is 0. More preferably, when m is 1 and p is 1 or 2, A 2 and A 3 are both C(R s )(R h ) or C(R 10 )(R n ), respectively. More preferably, m is 1 and p is 1. In the compounds of Formulas I to JV, R d and each R are preferably H, in the compounds of Formulas V to XI, each R 4 and R 6 are preferably H and in the compounds of Formula XHI, each R 6 is preferably H. Other embodiments of this invention comprise compounds having the formula: I wherein: R a is (C r C 4 )alkylcarbonyl-(C r C 4 )alkyl, (C 3 -C 8 )cycloaUcylcarbonyl-(C 1 -C 4 )alkyl, heteroarylcarbonyl-(C 1 -C 4 )aUcyl, ( -C^alkylcarbonylamino-^-C^alkyl, (C 3 -C 8 ) cycloaUcylcarbonylamino-(C 1 -C 4 )aUcyl, heterocycloalkylcarbonylamino-^ C aUcyl, arylcarbonylamino-(C 1 -C 4 )aUcyl, heteroarylcarbonylamino-(C r C 4 )aUcyl, (C,-C 4 aUcylaminocarbonyl-(C 1 -C 4 )aUcyl, (C 3 -C 8 )cycloaUcylaminocarbonyl-(C 1 -C 4 )aUcyl, heterocycloaUcylaminocarbonyl-(Cι-C 4 )aUcyl, arylaminocarbonyl-(C 1 -C 4 )alkyl, heteroarylaminocarbonyl-(C 1 -C 4 )alkyl, wherein each ( -C alkyl, (C 3 -C 8 )cycloaUcyl, heterocycloaUcyl, aryl and heteroaryl moiety thereof is unsubstituted or substituted with one or more suitable substituents; preferably R is (Cι-C 4 )alkylcarbonyl-(C 1 -C 4 )aU yl, (C 5 -C 6 )cycloaUcylcarbonyl-(C r C 4 )aUcyl, arylcarbonyl-(C r C 4 )aUcyl, heteroarylcarbonyl-(Ci-C 4 )alkyl, (Cι-C 4 )alkylcarbonylamino-(C 1 -C 4 )aUcyl, C 3 -C 8 cycloaUcylcarbonylamino-(C,-C 4 )aUcyl, heterocycloalkylcarbonylamino-^-C^alkyl, arylcarbonylamino-(Cι-C 4 )alkyl, heteroarylcarbonylamino-(C r C 4 )alkyl, (C ] -C 4 aUcylaminocarbonyl-(C r C 4 )aUcyl, (C 5 -C 6 )cycloalkylaminocarbonyl-(C r C 4 )aUcyl, heterocycloaUcylaminocarbonyl- (C r C 4 )alkyl, arylaminocarbonyl-(C 1 -C 4 )aUcyl, heteroarylaminocarbonyl-(Ci-C 4 )aUcyl, wherein each (C 3 -C 8 )cycloalkyl, heterocycloaUcyl, aryl and heteroaryl moiety thereof is unsubstituted or substituted with one or more suitable substituents; more preferably, R a is (C j -C^alkylcarbonyl^C j -C^alkyl, phenylcarbonyl-^ j -C aUcyl, naphthylcarbonyl-(C r C 4 )aUcyl, pyrrolylcarbonyl-(C 1 -C 4 )aUcyl, indolylcarbonyl-(C r C 4 )aUcyl, (C r C 4 )alkylcarbonylannno-(C r C 4 )alkyl, pyreolylcarbonylamino- C j - ^alkyl, indolylcarbonylamino-(C 1 -C 4 )aUcyl, phenylcarbonylamino-(C 1 -C 4 )aUcyl, naρhthylcarbonylamino-(C r C 4 )aUcyl, (C 1 -C 4 )aUcylaminocarbonyl-(C 1 -C 4 )aUcyl, pyrrolylammocarbonyl-(C 1 -C 4 )aUcyl, phenylaminocarbonyl-(C 1 -C 4 )aUcyl, naphthylaminocarbonyl-(C 1 -C 4 )alkyl, wherein each (C r C 4 )alkyl, phenyl, naphthyl, pyrrolyl, and indolyl moiety thereof is unsubstituted or substituted with one or more substituents independently selected from halo, C,-C 4 alkyl, C r C 4 haloalkyl, C r C 4 alkoxy, Cι-C 4 haloaUcoxy, methylenedioxy, aryl, heterocycloalkyl, and heteroaryl, where the aryl, heterocycloaUcyl or heteroaryl is unsubstituted or substituted by one ore more substituents independently selected from halo, - alkyl, C r C 4 haloalkyl, C r C 4 alkoxy, C j - haloalkoxy and methylenedioxy; and preferably, where said indolyl moiety thereof is substituted with one or two substituents independently selected from halo, - alkoxy, unsubstituted C r C 4 alkyl and C,-C 4 haloalkyl; R b and R d are each independently H or C,-C 4 alkyl; preferably R b and R d are each H; R c is selected from -CH 2 CH 2 C(O)NH 2 ; -CH 2 CH 2 C(O)NH-alkyl; -CH 2 NHC(O)CH 3 ; and , where n is 1 or 2; Z 1 is H or C r C 4 alkyl and Z is -CO 2 -alkyl, -CO 2 -cycloaUcyl, -CO 2 -aUcylaryl or -CO 2 -alkylheterocycloaryl, or Z 1 and Z taken together with the atom to which they are attached form preferably, Z 1 is H and Z is -CO 2 CH 2 CH 3 , -CO 2 (CH(CH 3 ) 2 ), -CO 2 (C(CH 3 ) 3 ), -CO 2 CH 2 (C(CH 3 ) 3 ), -CO 2 (cyclo-C 5 H 9 ) or Z 1 and Z taken together with the atom to which they are attached form more preferably Z 1 is H and Z is -CO 2 CH 2 CH 3 or 7) and Z taken together with the atom to which they are attached form provided that R c is , where n is 1 or 2, when R a is an indolylcarbonylamino-^-C alkyl group where the indolyl moiety thereof is substituted with one or more suitable substituents or R a is is not an amino-substituted (C r C 4 )alkylcarbonylamino-(C r C 4 )alkyl or R a is is not an amino-substituted (C 1 -C 4 )aUcylcarbonyl-(C 1 -C 4 )alkyl; and R c is selected from -CH 2 CH 2 C(O)NH 2 ; -CH 2 CH 2 C(O)NH-alkyl; -CH 2 NHC(O)CH 3 ; and where n is 1 or 2, when R a is an indolylcarbonylamino-(C r C 4 )alkyl group where the indolyl moiety thereof is unsubstituted or R a is a (C C 4 ) (C 3 -C 8 )cycloaUcylaminocarbonyl-(C 1 -C 4 )aUcyl, heterocycloaUcylaminocarbonyl- heteroarylaminocarbonyl-(Cι-C 4 )alkyl, or heteroarylcarbonylamino-(C 1 -C 4 )aUcyl group, wherein each (Cι~C 4 )alkyl, (C 3 -C 8 )cycloaUcyl, heterocycloaUcyl, aryl and heteroaryl moiety thereof is unsubstituted or substituted with one or more suitable substituents; or a prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate of said compound. Preferably, in the compounds of Formula I, as defined above, R c is , where n is 1, when R a is an indolylcarbonylamino-(C 1 -C 4 )alkyl group where the indolyl moiety thereof is substituted with one or two substituents independently selected from halo, - alkoxy, unsubstituted C r C 4 alkyl and - haloalkyl, C C 4 haloalkoxy, methylenedioxy, aryl, heterocycloaUcyl, and heteroaryl where the aryl, heterocycloaUcyl and heteroaryl is unsubstituted or substituted by one ore more substituents independently selected from halo, C]-C 4 alkyl, Cj-Q, haloalkyl, C r C 4 alkoxy, C r C 4 haloalkoxy and methylenedioxy; and R c is selected from -CH 2 CH 2 C(O)NH 2 ; -CH 2 CH 2 C(O)NH-alkyl; -CH 2 NHC(O)CH 3 ; and , where n is 1, when R a is (C r C 4 )alkylcarbonyl-(C r C 4 )aUcyl, (C 5 -C 6 )cycloalkyl carbonyl-(Cj-C 4 )alkyl, arylcarbonyl-(C r C 4 )aUcyl, heteroarylcarbonyl-(C 1 -C 4 )aUcyl, (Cι-C 4 )aUcylcarbonylamino-(C 1 -C 4 )aUcyl, C 3 -C 8 cycloalkylcarbonylamino-(C 1 -C 4 )alkyl, heterocycloalkylcarbonylamino-(C 1 -C 4 )aUcyl, arylcarbonylamino-(Cι-C 4 )aUcyl, heteroarylcarbonylamino-(C 1 -C 4 )aUcyl, (C 1 -C 4 aUcylaminocarbonyl-(C r C 4 )aUcyl, ^-C^cycloalkylaminocarbonyl-^j-C aUcyl, heterocycloaUcylaminocarbonyl- (C r C 4 )alkyl, arylaminocarbonyl-(C 1 -C 4 )alkyl, heteroarylaminocarbonyHCj-C alkyl, wherein each (C r C 4 )alkyl, (C 3 -C 8 )cycloaUcyl, heterocycloaUcyl, aryl and heteroaryl moiety thereof unsubstituted or substituted with one or more suitable substituents. More preferably, in the compounds of Formula I, as defined above, R° is , when R is an indolylcarbonylamino-(C 1 -C 4 )alkyl group where the indolyl moiety thereof is substituted with one or two substituents independently selected from halo, C C 4 alkoxy, unsubstituted C r C 4 alkyl and C C 4 haloalkyl; and and R c is -CH 2 CH 2 C(O)NH 2 or when R a is (C 1 -C 4 )aUcylcarbonyl-(C r C 4 )aUcyl, phenylcarbonyl-(Cι-C 4 )alkyl, naphthylcarbonyl-(C 1 -C 4 )aUcyl, pyrrolylcarbonyl-(C 1 -C 4 )aUcyl, indolylcarbonyl-(C C 4 )aUcyl, (C r C 4 )aUcylcarbonylamino-(C r C 4 )aUcyl, pyrrolylcarbonylamino-(C j -C 4 )aUcyl, indolylcarbonylamino-(C , -C 4 )alkyl, phenylcarbonylarnino-(C r C 4 )aUcyl, naphthylcarbonylamino-^ C^aUcyl, (C 1 -C 4 )alkylaminocarbonyl-(C 1 -C 4 )alkyl, phenylaminocarbonyl-^j-C^alkyl, naphthylaminocarbonyl-(C 1 -C 4 )aUcyl, wherein each phenyl, naphthyl and pyrrolyl moiety thereof is group is unsubstituted or substituted with one or more substituents independently selected from halo, C,-C 4 alkyl, C,-C 4 haloalkyl, C,-C 4 aUcoxy, C C 4 haloaUcoxy, methylenedioxy, aryl, heterocycloaUcyl, and heteroaryl, where the aryl, heterocycloaUcyl and heteroaryl is unsubstituted or substituted by one ore more substituents independently selected from halo, C r C 4 alkyl, C r C 4 haloalkyl, C ] -C 4 alkoxy, C r C 4 haloaUcoxy and methylenedioxy; and said indolyl moiety is unsubstituted. Other specific compounds of this invention have the formula: π R a ' is a (C 1 -C 4 )alkyl, (C 3 -C 8 )cycloalkyl, aryl or heteroaryl group, wherein the (C,-C 4 )alkyl, (C 3 -C 8 )cycloalkyl, aryl and heteroaryl group is unsubstituted or substituted with one or more substituents independently selected from (Cι-C 4 )alkyl, aryl, (C 3 -C 8 )cycloalkyl, heterocycloaUcyl, heteroaryl, halo, hydroxyl, (Cι-C 4 )alkoxy, aUcylenedioxy (as a substituent for aryl or heteroaryl), aryloxy, (C 3 -C 8 )cycloalkoxy, heteroaryloxy, and carboxyl where the (C r C 4 )alkyl, aryl, (C 3 -C 8 )cycloalkyl, heterocycloaUcyl, heteroaryl moieties thereof are optionally substituted by one or more of (C r C 4 )alkyl (except for alkyl), halo, (C r C 4 )haloalkyl, (C r C 4 )haloaUcoxy, aUcylenedioxy, aryl or heteroaryl, where the aryl or heteroaryl is unsubstituted or substituted with one or more substituents independently selected from alkyl, haloalkyl, aUcylenedioxy, nitro, amino, hyckoxamino, aUcylamino, diaUcylamino, halo, hydroxyl, alkoxy, haloaUcoxy, aryloxy, mercapto, alkylthio or arylthio groups; preferably, R a' is a (C r C 4 )alkyl, pyrrolyl, indolyl, phenyl or naphthyl group, where the (C 1 -C 4 )aUcyl group is unsubstituted or substituted with one or more substituents mdependently selected from halo, C r C 4 alkoxy or C,-C 4 haloaUcoxy and the pyrrolyl, indolyl, phenyl or naphthyl group is unsubstituted or substituted with one or more substituents independently selected from halo, C r C 4 alkyl, - haloalkyl, C r C 4 alkoxy, C r C 4 haloalkoxy, methylenedioxy, aryl, heterocycloalkyl and heteroaryl, where the aryl, heterocycloaUcyl and heteroaryl is unsubstituted or substituted by one or more substituents independently selected from halo, C r C 4 alkyl, -Q haloalkyl, C r C 4 alkoxy, C j -C 4 haloaUcoxy and methylenedioxy; more preferably, R a ' is an unsubstituted or a pyrrolyl, indolyl, phenyl or naphthyl group, where the pyrrolyl, indolyl, phenyl or naphthyl group is unsubstituted or substituted by one or more substituents independently selected from halo, C,-C 4 alkyl, C r C 4 haloalkyl or a phenyl, naphthyl, isoxazolyl, pyridyl, quinoyl or isoquinoyl group, where the phenyl, naphthyl, isoxazolyl, pyridyl, quinoyl or isoquinoyl group is unsubstituted or substituted with one or more substituents independently selected from halo, Cj-C 4 alkyl, C r C 4 haloalkyl, C r C 4 alkoxy, C C 4 haloaUcoxy and methylenedioxy; in specific embodiments, R a ' is an unsubstituted (Cj-C 4 )alkyl, pyrrolyl, indolyl, phenyl or naphthyl group or a pyrrolyl group substituted by phenyl, α-naphthyl, β-naphthyl, 2-chlorophenyl, 2-α,α, -trifluoromethylphenyl, 3-chloro-6-methoxyphenyl, 2,3-dichlorophenyl, 4-isoquinoyl, 3-iso-propylphenyl, 2,5-dimethoxyphenyl, 2-methoxyphenyl, 2-methylphenyl (o-tolyl), 2-bromophenyl, 3 -pyridyl, 4-pyridyl, 3-methyl-isoxazol-5-yl, 3,3,3-trifluoroprop-l-yl, or 2,3-benzo[d]dioxolyl or an indolyl group substituted by halo, C r C 4 aUcoxy, unsubstituted C r C 4 alkyl, Cj-Q haloalkyl, and C C 4 aUcoxyalkyl; n is 1, 2 or 3; preferably n is 1 or 2; more preferably, n is 2; R x is H and R y is H, C r C 4 alkyl, C r C 4 haloaUcyl or an arylalkyl, heteroarylalkyl, cycloaUcylaUcyl group or a straight-chain saturated hydrocarbon moiety or an unsaturated hydrocarbon moiety, where the arylalkyl, heteroarylalkyl, cycloaUcylaUcyl group is unsubstituted or substituted with one or more suitable substituents; preferably, R is H and R y is substituted or unsubstituted methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, 2-propen-l-yl, 2-propen-2-yl, 2-propyn- 1 -yl, 3 -methyl-3 -buten- 1 -yl, -methylcyclohexyl, -methylthienyl or benzyl, where the substituted methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, 2-ρropen-l-yl, 2-propen-2-yl, 2-propyn-l-yl, 3-methyl-3-buten-l-yl, and -methylcyclohexyl is substituted by one or more substituents independently selected from halo, alkoxy, aryloxy, alkylthio and arylthio; the subsituted thienyl is substituted by one or more substituents independently selected from lower alkyl, lower alkoxy, hydroxy, amino, alkylamino, diaUcylamino and halo; and the phenyl moiety ofthe substituted benzyl is substituted by one or more substituents independently selected from lower alkyl, lower alkoxy, aUcylenedioxy, hydroxy, amino, aUcylamino, diaUcylamino and halo; more preferably, R is H and R y is ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, 2-propen-l-yl, 2-propen-2-yl, 2-propyn-l-yl, 3 -methyl-3 -buten- 1-yl, -methylcyclohexyl, benzyl or substituted benzyl, wherein the phenyl moiety ofthe substituted benzyl comprises one or more substituents independently selected from C C 4 alkyl, C C 4 alkoxy and halo; even more preferably, where R x is H and R y is H, ethyl, 2-propyn-l-yl, methylcyclohexyl or benzyl; R c is , where n is 1 or 2; preferably R c is R , R d , Z and Z 1 are defined as in Formula I, above. Yet other specific compounds of this invention have the formula: m wherein: R ' is a (C r C 4 )alkyl, (C 3 -C 8 )cycloalkyl, aryl or heteroaryl group, wherein the (C 1 -C 4 )aUcyl, (C 3 -C 8 )cycloaUcyl, aryl and heteroaryl group is unsubstituted or substituted with one or more suitable substituents provided that R a ' is not an amino- substituted ( -C^alkyl group; preferably, R a ' is a (Cj-C alkyl, phenyl, naphthyl, pyrrolyl or indolyl group, where the (C j -C 4 )alkyl group is unsubstituted or substituted with one or more substituents independently selected from halo, C r C 4 alkoxy or C r C 4 haloalkoxy and the phenyl, naphthyl, pyrrolyl or indolyl group is unsubstituted or substituted with one or more substituents independently selected from halo, Cj-C 4 alkyl, C C 4 haloalkyl, C r C 4 alkoxy, C r C 4 haloaUcoxy, methylenedioxy, aryl, heterocycloaUcyl, and heteroaryl, where the aryl, heterocycloaUcyl or heteroaryl is unsubstituted or substituted by one ore more substituents independently selected from halo, - alkyl, C r C 4 haloalkyl, C r C 4 alkoxy, Cj-C 4 haloaUcoxy and methylenedioxy; more preferably, R a ' is a pyrrolyl or indolyl group, where the pyrrolyl or indolyl group is unsubstituted or substituted by one or more substituents independently selected from halo, C r C 4 alkyl, C r C 4 haloalkyl or a phenyl, naphthyl, isoxazolyl, pyridyl, quinoyl or isoquinoyl group, where the phenyl, naphthyl, isoxazolyl, pyridyl, quinoyl or isoquinoyl group is unsubstituted or substituted with one or more substituents independently selected from halo, C C 4 aUcyl, - haloalkyl, C r C 4 aUcoxy, C r C 4 haloaUcoxy and methylenedioxy; even more preferably, R a' is a pyrrolyl group that is unsubstituted or substituted by phenyl, α-naphthyl, β-naphthyl, 2-chlorophenyl, 2-α,α,α-trifluoromethylphenyl, 3-chloro-6- methoxyphenyl, 2,3-dichlorophenyl, 4-isoquinoyl, 3-iso-propylphenyl, 2,5-dimethoxyphenyl, 2-methoxyphenyl, 2-methylphenyl (o-tolyl), 2-bromophenyl, 3-pyridyl, 4-pyridyl, 3-methyl-isoxazol-5-yl, 3,3,3-trifluoroprop-l-yl, or 2,3-benzo[d]dioxolyl; n is 1, 2 or 3; preferably n is 1 ; R x is H and R y is H, C r C 4 alkyl, C r C 4 haloaUcyl or an arylalkyl, heteroarylalkyl, cycloaUcylaUcyl group or a straight-chain saturated hydrocarbon moiety or an unsaturated hydrocarbon moiety, where the arylalkyl, heteroarylalkyl, cycloaUcylaUcyl group is unsubstituted or substituted with one or more suitable substituents; preferably, R x is H and R y is substituted or unsubstituted methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, 2-propen-l-yl, 2-propen-2-yl, 2-propyn-l-yl, 3 -methyl-3 -buten- 1-yl, -methylcyclohexyl, -methylthienyl or benzyl, where the substituted methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, 2-propen-l-yl, 2-propen-2-yl, 2-propyn-l-yl, 3 -methyl-3 -buten- 1-yl, and -methylcyclohexyl is substituted by one or more substituents independently selected from halo, alkoxy, aryloxy, alkylthio and arylthio; the subsituted thienyl is substituted by one or more substituents independently selected from lower alkyl, lower alkoxy, hydroxy, amino, aUcylamino, dialkylamino and halo; and the phenyl moiety ofthe substituted benzyl is substituted by one or more substituents independently selected from lower alkyl, lower alkoxy, aUcylenedioxy, hydroxy, amino, aUcylamino, diaUcylamino and halo; more preferably, R x is H and R y is ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, 2-propen-l-yl, 2-propen-2-yl, 2-propyn-l-yl, 3 -methyl-3 -buten- 1-yl, -methylcyclohexyl, benzyl or substituted benzyl, wherein the phenyl moiety ofthe substituted benzyl comprises one or more substituents independently selected from C r C 4 alkyl, C r C 4 alkoxy and halo; even more preferably, where R x is H and R y is H, ethyl, 2-propyn-l-yl, methylcyclohexyl or benzyl; R c is , where n is 1 or 2; preferably R c is 1 ; more preferably, R c is and R b , R d , Z and Z 1 are defined as in Formula I, above. Another embodiment of this invention comprises compounds having the formula: rv wherein: R a ' is a (C j -C alkyl, (C 3 -C 8 )cycloaUcyl, heterocycloalkyl, aryl or heteroaryl group, wherein the (C 1 -C 4 )alkyl, (C 3 -C 8 )cycloalkyl, heterocycloaUcyl, aryl and heteroaryl group is unsubstituted or substituted with one or more suitable substituents; preferably, R ' is a (C r C 4 )alkyl, phenyl or naphthyl group, where the (C r C 4 )alkyl group is unsubstituted or substituted with one or more substituents independently selected from halo, C C 4 alkoxy or C C 4 haloaUcoxy and the phenyl or naphthyl group is unsubstituted or substituted with one or more substituents independently selected from halo, C r C 4 alkyl, C C 4 haloalkyl, C r C 4 alkoxy, C r C 4 haloaUcoxy, methylenedioxy and phenyl, where the phenyl is unsubstituted or substituted by one or more substituents independently selected from halo, C r C 4 alkyl, C r C 4 haloalkyl, C r C 4 alkoxy, C r C 4 haloaUcoxy and methylenedioxy; in specific embodiments, R a' is a halo-substituted phenyl group; n is 1, 2 or 3; preferably, n is 1 or 2; more preferably, n is 1 ; R x is H and R y is H, C r C 4 alkyl, C r C 4 haloalkyl or an arylalkyl, heteroarylalkyl, cycloaUcylaUcyl group or a straight-chain saturated hydrocarbon moiety or an unsaturated hydrocarbon moiety, where the arylalkyl, heteroarylalkyl, cycloaUcylaUcyl group is unsubstituted or substituted with one or more suitable substituents; preferably, R x is H and R y is substituted or unsubstituted methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, 2-propen-l-yl, 2-propen-2-yl, 2-propyn-l-yl, 3 -methyl-3 -buten- 1-yl, -methylcyclohexyl, -methylthienyl or benzyl, where the substituted methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, 2-propen-l-yl, 2-propen-2-yl, 2-propyn-l-yl, 3 -methyl-3 -buten- 1-yl, and -methylcyclohexyl is substituted by one or more substituents independently selected from halo, alkoxy, aryloxy, aUcylthio and arylthio; the subsituted thienyl is substituted by one or more substituents independently selected from lower alkyl, lower alkoxy, hydroxy, amino, aUcylamino, dialkylamino and halo; and the phenyl moiety ofthe substituted benzyl is substituted by one or more substituents independently selected from lower alkyl, lower alkoxy, aUcylenedioxy, hydroxy, amino, alkylamino, diaUcylamino and halo; more preferably, R x is H and R y is ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, 2-propen-l-yl, 2-propen-2-yl, 2-propyn-l-yl, 3 -methyl-3 -buten- 1-yl, -methylcyclohexyl, benzyl or substituted benzyl, wherein the phenyl moiety ofthe substituted benzyl comprises one or more substituents independently selected from C r C 4 alkyl, C r C 4 alkoxy and halo; even more preferably, where R x is H and R y is H, ethyl, 2-propyn-l-yl, methylcyclohexyl or benzyl; and and R b , R c , R d , Z and Z 1 are defined as in Formula I, above. Other specific embodiments of this invention comprise the compounds having the formula: VI wherein: W is CH orN; R a ' is a C C 4 alkyl, C 3 -C 8 cycloaUcyl, aryl or heteroaryl group, where the C C 4 alkyl, C 3 -C 8 cycloaUcyl, aryl, and heteroaryl group is unsubstituted or substituted with one or more suitable substituents, provided that R a ' is not an amino-substituted alkyl group; preferably, R a' is a C r C 4 alkyl, C 5 -C 6 cycloaUcyl, phenyl, naphthyl or heteroaryl group; where the phenyl, naphthyl or heteroaryl group is unsubstituted or substituted with one or more substituents independently selected from halo, C C 4 alkyl, Cj- haloaUcyl, C r C 4 alkoxy, C r C 4 haloaUcoxy, methylenedioxy, aryl, heterocycloalkyl, and heteroaryl, where the aryl, heterocycloalkyl and heteroaryl is unsubstituted or substituted by one ore more substituents independently selected from halo, Cj-C 4 alkyl, C r C 4 haloalkyl, Cj-C 4 alkoxy, C C 4 haloalkoxy and methylenedioxy; more preferably, R a' is a C r C 4 alkyl, C 5 -C 6 cycloaUcyl, phenyl, naphthyl, pyrrolyl or indolyl, group, where the phenyl, naphthyl, pyrrolyl or indolyl, group is unsubstituted or substituted with one or more substituents independently selected from halo, Cj-C 4 alkyl, C,-C 4 haloaUcyl, C r C 4 alkoxy, - haloaUcoxy, methylenedioxy and a phenyl, naphthyl, isoquinoyl, pyridyl or isoxazolyl group, wherein the phenyl, naphthyl, isoquinoyl, pyridyl and isoxazolyl group is unsubstituted or substituted by one ore more substituents independently selected from halo, -C 4 alkyl, C C 4 haloaUcyl, Cj- C 4 alkoxy, C r C 4 haloaUcoxy and methylenedioxy; R 4 and R 6 are each independently H or C r C 4 alkyl; preferably R 4 and R 6 are eachH; R 5 is H, C C 4 alkyl, C,-C 4 haloaUcyl or an arylalkyl, heteroarylalkyl, cycloaUcylaUcyl group or a straight-chain saturated hydrocarbon moiety or an unsaturated hydrocarbon moiety, where the arylalkyl, heteroarylalkyl, cycloaUcylaUcyl group is unsubstituted or substituted with one or more suitable substituents; preferably, R 5 is H or substituted or unsubstituted methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, 2-propen-l-yl, 2-ρroρen-2-yl, 2-propyn-l-yl, 3-methyl-3-buten-l-yl, -methylcyclohexyl, -methylthienyl or benzyl, where the substituted methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, 2-propen-l-yl, 2-propen-2-yl, 2-propyn-l-yl, 3-methyl-3-buten-l-yl, and -methylcyclohexyl is substituted by one or more substituents independently selected from halo, alkoxy, aryloxy, aUcylthio and arylthio; the subsituted thienyl is substituted by one or more substituents independently selected from lower alkyl, lower alkoxy, hydroxy, amino, aUcylamino, diaUcylamino and halo; and the phenyl moiety ofthe substituted benzyl is substituted by one or more substituents independently selected from lower alkyl, lower alkoxy, aUcylenedioxy, hydroxy, amino, alkylamino, diaUcylamino and halo; more preferably, R 5 is H, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, 2-propen-l-yl, 2-propen-2-yl, 2-propyn-l-yl, 3 -methyl-3 -buten- 1-yl, -methylcyclohexyl, benzyl or substituted benzyl, wherein the phenyl moiety ofthe substituted benzyl comprises one or more substituents independently selected from C,-C 4 alkyl, C C 4 alkoxy and halo; even more preferably, R 5 is H, ethyl, 2-propyn-l-yl, methylcyclohexyl or benzyl; R 7 is , where n is 1 or 2; preferably, R 7 is is 1; most preferably, R 7 is and Z 1 is H or C r C 4 alkyl and Z is -CO 2 -alkyl, -CO 2 -cycloalkyl, -CO 2 -alkylaryl or -CO 2 -aUcylheterocycloaryl, or Z 1 and Z taken together with the atom to which they are attached form preferably, Z 1 is H and Z is -CO 2 CH 2 CH 3 , -CO 2 (CH(CH 3 ) 2 ), -CO 2 (C(CH 3 ) 3 ), -CO 2 CH 2 (C(CH 3 ) 3 ), -CO 2 (cyclo-C 5 H 9 ) or Z 1 and Z taken together with the atom to which they are attached form most preferably, Z 1 is H and Z is -CO 2 CH 2 CH 3 or Z 1 and Z taken together with the atom to which they are attached form or a prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate of said compound. Specific embodiments of Formula VI of this invention comprise the compounds depicted by the formula: VH and the compounds depicted by the formula: vm wherein R a' , R 4 , R 3 , R 6 , R 7 , Z and Z 1 are as defined above. In addition, specific embodiments of this invention comprise the compounds depicted by the formula: rx wherein: R 1 is H, halo, C r C 4 alkyl, C r C 4 haloalkyl, or an aryl or heteroaryl group, where the aryl or heteroaryl group is unsubstituted or substituted with one or more suitable substituents; preferably, R 1 is H, halo, Cj-C 4 alkyl, Cj-C 4 haloalkyl or a phenyl, naphthyl, isoxazolyl, pyridyl, quinoyl or isoquinoyl group, where the phenyl, naphthyl, isoxazolyl, pyridyl, quinoyl or isoquinoyl group is unsubstituted or substituted with one or more substituents independently selected from: halo, C,-C 4 alkyl, C r C 4 haloaUcyl, C r C 4 alkoxy, C r C 4 haloaUcoxy and methylenedioxy; more preferably, R 1 is H, phenyl, α-naphthyl, β-naphthyl, 2-chlorophenyl, 2-α, ,α-trifluoromethylphenyl, 3-chloro-6-methoxyphenyl, 2,3-dichlorophenyl, 4-isoquinoyl, 3-iso-propylphenyl, 2,5-dimethoxyphenyl, 2-methoxyphenyl, 2-methylphenyl (o-tolyl), 2-bromophenyl, 3-pyridyl, 4-pyridyl, 3-methyl-isoxazol-5-yl, 3,3,3-trifluoroprop-l-yl, or 2,3-benzo[d]dioxolyl; R 2 and R 3 are each independently H or Cj-C 4 aUcyl; preferably R 2 and R 3 are each H; or R 1 together with R 2 form a cycloaUcyl, heterocycloaUcyl, aryl or heteroaryl ring, where the cycloaUcyl, heterocycloaUcyl, aryl or heteroaryl ring is unsubstituted or substituted with one or more suitable substituents; or preferably, R 1 together with R 2 form a phenyl ring, which is unsubstituted or substituted with one or more suitable substituents and R 3 is H; R 4 and R 6 are each independently H or Cj-C 4 alkyl; preferably R 4 and R 6 are each H; R 5 is H, C r C 4 aUcyl, C -C 4 haloalkyl or an arylalkyl, heteroarylalkyl, cycloaUcylaUcyl group or a straight-chain saturated hydrocarbon moiety or an unsaturated hydrocarbon moiety, where the arylalkyl, heteroarylalkyl, cycloaUcylaUcyl group is unsubstituted or substituted with one or more suitable substituents; preferably, R 5 is H or substituted or unsubstituted methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, 2-propen-l-yl, 2-propen-2-yl, 2-propyn-l-yl, 3-methyl-3-buten-l-yl, -methylcyclohexyl, -methylthienyl or benzyl, where the substituted methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, 2-propen-l-yl, 2-propen-2-yl, 2-propyn-l-yl, 3 -methyl-3 -buten- 1-yl, and -methylcyclohexyl is substituted by one or more substituents independently selected from halo, alkoxy, aryloxy, alkylthio and arylthio; the subsituted thienyl is substituted by one or more substituents independently selected from lower alkyl, lower alkoxy, hydroxy, amino, aUcylamino, diaUcylamino and halo; and the phenyl moiety ofthe substituted benzyl is substituted by one or more substituents independently selected from lower alkyl, lower alkoxy, aUcylenedioxy, hydroxy, amino, aUcylamino, dialkylamino and halo; more preferably, R 5 is H, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, 2-propen-l-yl, 2-propen-2-yl, 2-propyn-l-yl, 3 -methyl-3 -buten- 1-yl, -methylcyclohexyl, benzyl or substituted benzyl, wherein the phenyl moiety ofthe substituted benzyl comprises one or more substituents independently selected from C r C 4 alkyl, C r C 4 alkoxy and halo; even more preferably, R 5 is H, ethyl, 2-propyn-l-yl, methylcyclohexyl or benzyl; R 7 is selected from -CH 2 CH 2 C(O)NH 2 ; -CH 2 CH 2 C(O)NH-alkyl; -CH 2 NHC(O)CH 3 ; and here n is 1 or 2; preferably, R 7 is -CH 2 CH 2 C(O)NH 2 where n is i; most preferably, R 7 is -CH 2 CH 2 C(O)NH 2 or and Z 1 is H or C C 4 alkyl and Z is -CO 2 -alkyl, -CO 2 -cycloaUcyl, -CO 2 -alkylaryl or -CO 2 -alkylheterocycloaryl, or Z 1 and Z taken together with the atom to which they are attached form , preferably, Z 1 is H and Z is -CO 2 CH 2 CH 3 , -CO 2 (CH(CH 3 ) 2 ), -CO 2 (C(CH 3 ) 3 ), -CO 2 CH 2 (C(CH 3 ) 3 ), -CO 2 (cyclo-C 5 H 9 ) or Z 1 and Z taken together with the atom to which they are attached form most preferably, Z 1 is H and Z is -CO 2 CH 2 CH 3 or Z 1 and Z taken together with the atom to which they are attached form or a prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate of said compound. Another specific embodiment of this invention comprises the compounds depicted by the formula: X wherein: R 1 is H, halo, C r C 4 alkyl, C r C 4 haloaUcyl, or an aryl or heteroaryl group, where the aryl or heteroaryl group is unsubstituted or substituted with one or more suitable substituents; preferably, R 1 is H, halo, C r C 4 alkyl, -Q, haloaUcyl or a phenyl, naphthyl, isoxazolyl, pyridyl, quinoyl or isoquinoyl group, where the phenyl, naphthyl, isoxazolyl, pyridyl, quinoyl or isoquinoyl group is unsubstituted or substituted with one or more substituents independently selected from: halo, C C 4 alkyl, C r C 4 haloaUcyl, C r C 4 alkoxy, Cj- haloalkoxy and methylenedioxy; more preferably, R 1 is H, phenyl, α-naphthyl, β-naphthyl, 2-chlorophenyl, 2-α,α,α-trifluoromethylphenyl, 3-chloro-6-methoxyphenyl, 2,3-dichlorophenyl, 4-isoquinoyl, 3-iso-propylphenyl, 2,5-dimethoxyphenyl, 2-methoxyphenyl, 2-methylphenyl (o-tolyl), 2-bromophenyl, 3-pyridyl, 4-pyridyl, 3-methyl-isoxazol-5-yl, 3,3,3-trifluoroprop-l-yl, or 2,3-benzo[d]dioxolyl; R 2 and R 3 are each independently H or C r C 4 alkyl; preferably R 2 and R 3 are each H; or R 1 together with R 2 form a cycloalkyl, heterocycloalkyl, aryl or heteroaryl ring, where the cycloaUcyl, heterocycloaUcyl, aryl or heteroaryl ring is unsubstituted or substituted with one or more suitable substituents; or preferably, R 1 together with R 2 form an unsubstituted phenyl ring and R 3 is H; R 4 and R 6 are each independently H or C r C 4 alkyl; preferably R 4 and R 6 are each H; R 5 is H, C r C 4 alkyl, C r C 4 haloalkyl or an arylalkyl, heteroarylalkyl, cycloaUcylaUcyl group or a straight-chain saturated hydrocarbon moiety or an unsaturated hydrocarbon moiety, where the arylalkyl, heteroarylalkyl, cycloaUcylaUcyl group is unsubstituted or substituted with one or more suitable substituents; preferably, R 5 is H or substituted or unsubstituted methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, 2-propen-l-yl, 2-propen-2-yl, 2-propyn-l-yl, 3-methyl-3-buten-l-yl, -methylcyclohexyl, -methylthienyl or benzyl, where the substituted methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, 2-propen-l-yl, 2-propen-2-yl, 2-propyn-l-yl, 3-methyl-3-buten-l-yl, and -methylcyclohexyl is substituted by one or more substituents independently selected from halo, alkoxy, aryloxy, alkylthio and arylthio; the subsituted thienyl is substituted by one or more substituents independently selected from lower alkyl, lower alkoxy, hydroxy, amino, aUcylamino, diaUcylamino and halo; and the phenyl moiety ofthe substituted benzyl is substituted by one or more substituents independently selected from lower alkyl, lower alkoxy, aUcylenedioxy, hydroxy, amino, aUcylamino, dialkylamino and halo; more preferably, R 5 is H, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, 2-propen-l-yl, 2-propen-2-yl, 2-propyn-l-yl, 3 -methyl-3 -buten- 1-yl, -methylcyclohexyl, benzyl or substituted benzyl, wherein the phenyl moiety ofthe substituted benzyl comprises one or more substituents independently selected from C r C 4 alkyl, C C 4 alkoxy and halo; even more preferably, R 5 is H, ethyl, 2-propyn-l-yl, methylcyclohexyl or benzyl; R 7 is selected from -CH 2 CH 2 C(O)NH 2 ; -CH 2 CH 2 C(O)NH-aUcyl; most preferably, R 7 is -CH 2 CH 2 C(O)NH 2 or provided that when R 1 together with R 2 form a phenyl ring and the phenyl ring is substituted, R 7 is selected from here n is 1 or 2, where n is i, or and Z 1 is H or C r C 4 alkyl and Z is -CO 2 -alkyl, -CO 2 -cycloalkyl, -CO 2 -aUcylaryl or -CO 2 -alkylheterocycloaryl, or Z 1 and Z taken together with the atom to which they are attached form , preferably, Z 1 is H and Z is -CO 2 CH 2 CH 3 , -CO 2 (CH(CH 3 ) 2 ), -CO 2 (C(CH 3 ) 3 ), -CO 2 CH 2 (C(CH 3 ) 3 ), -CO 2 (cyclo-C 5 H 9 ) or Z 1 and Z taken together with the atom to wliich they are attached form most preferably, Z 1 is H and Z is -CO 2 CH 2 CH 3 or Z 1 and Z taken together with the atom to which they are attached form or a prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate of said compound. Yet another specific embodiment of this invention comprises the compounds depicted by the formula: XI wherein: each R z is independently selected from halo and a C ι -C 4 alkoxy, - alkyl, aryl, heterocycloaUcyl or heteroaryl group where the C C 4 alkoxy or C r C 4 alkyl group is unsubstituted or substituted with one or more substituents independently selected from halo, C r C 4 alkoxy or C r C 4 haloalkoxy and the aryl, heterocycloaUcyl or heteroaryl group is unsubstituted or substituted by one ore more substituents independently selected from halo, C r C 4 alkyl, C r C 4 haloaUcyl, C r C 4 alkoxy, Cj- haloaUcoxy and methylenedioxy and n z is an integer from 1 to 4; preferably, each R z is independently selected from halo, C r C 4 alkoxy, unsubstituted C r C 4 alkyl, C C 4 haloaUcyl, and -C 4 alkoxyalkyl and n z is an mteger from 1 to 2; more preferably, each R z is independently selected from halo, C r C 4 alkoxy, unsubstituted C r C 4 alkyl and C r C 4 haloaUcyl, and n z is 1 or 2; R 3 is H, halo, C r C 4 alkoxy, unsubstituted C r C 4 alkyl, C r C 4 haloaUcyl and Cj-Q, alkoxyalkyl; preferably, R 3 is H or C r C 4 alkyl; more preferably, R 3 is H ; R 4 and each R 6 are independently selected from H, unsubstituted lower alkyl, haloalkyl and lower alkoxyalkyl, preferably, R 4 and each R 6 are independently H or C r C 4 alkyl; more preferably R 4 and R 6 are each H; R 5 is H, C ] -C 4 aUcyl, C,-C 4 haloaUcyl or an arylalkyl, heteroarylalkyl, cycloaUcylaUcyl group or a straight-chain saturated hydrocarbon moiety or an unsaturated hydrocarbon moiety, where the arylalkyl, heteroarylalkyl, cycloaUcylaUcyl group is unsubstituted or substituted with one or more suitable substituents; preferably, R 5 is H or substituted or unsubstituted methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, 2-propen-l-yl, 2-propen-2-yl, 2-propyn-l-yl, 3 -methyl-3 -buten- 1 -yl, -methylcyclohexyl, -methylthienyl or benzyl, where the substituted methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, 2-propen-l-yl, 2-propen-2-yl, 2-propyn-l-yl, 3 -methyl-3 -buten- 1-yl, and -methylcyclohexyl is substituted by one or more substituents independently selected from halo, alkoxy, aryloxy, aUcylthio and arylthio; the subsituted thienyl is substituted by one or more substituents independently selected from lower alkyl, lower alkoxy, hydroxy, amino, aUcylamino, dialkylamino and halo; and the phenyl moiety ofthe substituted benzyl is substituted by one or more substituents independently selected from lower alkyl, lower alkoxy, aUcylenedioxy, hydroxy, amino, aUcylamino, diaUcylamino and halo; more preferably, R 5 is H, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, 2-propen-l-yl, 2-propen-2-yl, 2-propyn-l-yl, 3 -methyl-3 -buten- 1-yl, -methylcyclohexyl, benzyl or substituted benzyl, wherein the phenyl moiety ofthe substituted benzyl comprises one or more substituents independently selected from Cj-C 4 alkyl, C x -C 4 alkoxy and halo; even more preferably, R s is H, ethyl, 2-propyn-l-yl, methylcyclohexyl or benzyl; Z 1 is H or C r C 4 alkyl and Z is -CO 2 -alkyl, -CO 2 -cycloaUcyl, -CO 2 -aUcylaryl or -CO 2 -alkylheterocycloaryl, or Z 1 and Z taken together with the atom to which they are attached form , preferably, Z 1 is H and Z is -CO 2 CH 2 CH 3 , -CO 2 (CH(CH 3 ) 2 ), -CO 2 (C(CH 3 ) 3 ), -CO 2 CH 2 (C(CH 3 ) 3 ), -CO 2 (cyclo-C 5 H 9 ) or Z 1 and Z taken together with the atom to which they are attached form most preferably, Z 1 is H and Z is -CO 2 CH 2 CH 3 or Z 1 and Z taken together with the atom to which they are attached form or a prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate of said compound. Another preferred embodiment of this invention comprises the compounds of Formula XH, depicted by the formula: XH wherein: R a' is a C r C 4 alkyl, aryl, C 3 -C 7 cycloaUcyl, heterocycloaUcyl or heteroaryl group, where the C r C 4 alkyl, aryl, C 3 -C 7 cycloaUcyl, heterocycloaUcyl or heteroaryl group is unsubstituted or substituted with one or more substituents independently selected from alkyl, haloalkyl, aUcylenedioxy (as a substituent for aryl or heteroaryl), nitro, amino, hydroxamino, aUcylamino, dialkylamino, halo, hydroxyl, alkoxy, haloaUcoxy, aryloxy, mercapto, alkylthio or arylthio, aryl or heteroaryl, where the aryl or heteroaryl group is unsubstituted or substituted with one or more substituents independently selected from halo, C r C 4 alkyl, C r C 4 haloaUcyl, C,-C 4 alkoxy, C C 4 haloalkoxy and methylenedioxy; preferably, R a' is a C r C 4 alkyl, C r C 4 haloaUcyl, phenyl, naphthyl, C 5 -C 6 cycloalkyl, isoquinoyl, pyridyl or pyrrolyl group, where the phenyl, naphthyl, isoquinoyl, pyridyl or pyrrolyl group is unsubstituted or substituted with one or more substituents independently selected from halo, C r C 4 alkyl, C r C 4 haloalkyl, C r C 4 alkoxy, - haloaUcoxy and methylenedioxy; more preferably, R a' is a phenyl group, where the phenyl group is unsubstituted or substituted with one or more substituents independently selected from halo, Cj- alkyl, C C 4 haloalkyl or C r C 4 alkoxy; each R 6 is independently H or C r C 4 alkyl; preferably, each R 6 is H; R 5 is H, C C alkyl, C r C 4 haloaUcyl or an arylalkyl, heteroarylalkyl, cycloaUcylaUcyl group or a straight-chain saturated hydrocarbon moiety or an unsaturated hydrocarbon moiety, where the arylalkyl, heteroarylalkyl, cycloaUcylaUcyl group is unsubstituted or substituted with one or more suitable substituents; preferably, R 5 is H or substituted or unsubstituted methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, 2-propen-l-yl, 2-propen-2-yl, 2-propyn-l-yl, 3 -methyl-3 -buten- 1-yl, -methylcyclohexyl, -methylthienyl or benzyl, where the substituted methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, 2-propen-l-yl, 2-propen-2-yl, 2-propyn-l-yl, 3 -methyl-3 -buten- 1-yl, and -methylcyclohexyl is substituted by one or more substituents independently selected from halo, alkoxy, aryloxy, alkylthio and arylthio; the subsituted thienyl is substituted by one or more substituents independently selected from lower alkyl, lower alkoxy, hydroxy, amino, alkylamino, dialkylamino and halo; and the phenyl moiety ofthe substituted benzyl is substituted by one or more substituents independently selected from lower alkyl, lower alkoxy, aUcylenedioxy, hydroxy, amino, aUcylamino, dialkylamino and halo; more preferably, R 5 is H, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, 2-propen-l-yl, 2-propen-2-yl, 2-propyn-l-yl, 3 -methyl-3 -buten- 1-yl, -methylcyclohexyl, benzyl or substituted benzyl, wherein the phenyl moiety ofthe substituted benzyl comprises one or more substituents independently selected from C r C 4 alkyl, C r C 4 alkoxy and halo; even more preferably, R 5 is H, ethyl, 2-propyn-l-yl, methylcyclohexyl or benzyl; R 7 is selected from -CH 2 CH 2 C(O)NH 2 ; -CH 2 CH 2 C(O)NH-alkyl; -CH 2 NHC(O)CH 3 ; and where n is 1 or 2; preferably, R 7 is -CH 2 CH 2 C(O)NH 2 or , where n is 1; most preferably, R 7 is -CH 2 CH 2 C(O)NH 2 or ; and Z 1 is H or C r C 4 alkyl and Z is -CO 2 -alkyl, -CO 2 -cycloaUcyl, -CO 2 -aUcylaryl or -CO 2 -alkylheterocycloaryl, or Z 1 and Z taken together with the atom to which they are attached form , preferably, Z 1 is H and Z is -CO 2 CH 2 CH 3 , -CO 2 (CH(CH 3 ) 2 ), -CO 2 (C(CH 3 ) 3 ), -CO 2 CH 2 (C(CH 3 ) 3 ), -CO 2 (cyclo-C 5 H 9 ) or Z 1 and Z taken together with the atom to which they are attached form most preferably, Z 1 is H and Z is -CO 2 CH 2 CH 3 or Z 1 and Z taken together with the atom to which they are attached form or a prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate of said compound. Preferred embodiments of this invention comprise the compounds depicted by the formula: Vl-a wherein R a ' is an alkyl, cycloaUcyl, aryl or heteroaryl group, where said alkyl, cycloaUcyl, aryl, and heteroaryl group is unsubstituted or substituted with one or more suitable substituents, and each W, R 4 , R 5 , R 6 , R 7 , Z and Z 1 are as defined in VI above, provided that R ' is not amino-substituted alkyl. Particularly preferred embodiments ofthe compounds of Formula Vl-a comprise the compounds depicted by the formula: VH-a wherein R a ' is an alkyl, cycloaUcyl, aryl or heteroaryl group, where said alkyl, cycloalkyl, aryl, and heteroaryl group is unsubstituted or substituted with one or more suitable substituents, and each R 4 , R 5 , R 6 , R 7 , Z and Z 1 are as defined above, provided that R a' is not amino-substituted alkyl. Other preferred embodiments ofthe compounds of Formula Vl-a comprise the compounds depicted by the formula: wherein R a ' is an alkyl, cycloalkyl, aryl or heteroaryl group, where said alkyl, cycloaUcyl, aryl, and heteroaryl group is unsubstituted or substituted with one or more suitable substituents, and each R 4 , R 5 , R 6 , R 7 , Z and Z 1 are as defined above, provided that R a' is not amino-substituted alkyl. More preferably, the compounds of this invention have the formula: K-a wherein R 1 is an alkyl, cycloaUcyl, heterocycloaUcyl, aryl or heteroaryl group, where the alkyl, cycloaUcyl, heterocycloaUcyl, aryl, and heteroaryl group is unsubstituted or substituted with one or more suitable substituents, and each R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , Z and Z 1 are as defined above for IX. In another preferred embodiment, the compounds of this invention have the formula: X-a wherein each R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , Z and Z 1 are as defined above. Yet another preferred embodiment of this invention comprises the compounds depicted by the formula: Xl-a wherein each R z , R 3 , R 4 , R 5 , R 6 , Z and Z 1 are as defined above and R 7 is a moiety having the formula: wherein each R , R , A l5 A 2 , A 3 , A 4 and p are as defined above. Another particularly preferred embodiment of this invention comprises the compounds depicted by the formula: XH-a wherein each R a ', R 5 , R 6 , R 7 , Z and Z 1 are as defined above. More preferably, R 5 is H and the invention comprises the compounds depicted by the formula: xπ-b wherein each R a , R 6 , R 7 , Z and Z 1 are as defined above. In the compounds of Formulas Vl-a to XH-b, R 6 is preferably H. In the compounds of Formulas Vl-a to Xl-a, each R 4 and R 6 is preferably H. Preferred specific compounds include those of any ofthe Examples below, especially: 10 10 Preferred specific embodiments ofthe compounds of this invention include any one ofthe following: and The invention is also directed to intermediate compounds of Formula XIH which are useful in the synthesis of certain compounds of Formulas I-XH: x wherein R 5 ' is a lower alkyl or aryl group, where the lower alkyl or aryl group is unsubstituted or substituted with one or more suitable substituents, (where -CH 2 -R 5 ' represents R 5 as defined above) and R E is H or an alkyl or aryl group, where the alkyl or aryl group is unsubstituted or substituted with one or more suitable substituents. The invention is also directed to pharmaceutically acceptable salts ofthe compounds of Formulas XIH. Preferred examples ofthe compounds of Formula XHI, include the following: and pharmaceutically acceptable salts thereof. Exemplary preferred R E groups include, but are not limited to, H, methyl, tert-butyl, allyl, and benzyl, as illustrated in the following: HCr-γDBn H The antipicornaviral compounds of this invention include prodrags, the pharmaceutically active metabolites, and the pharmaceutically acceptable salts and solvates thereof. In preferred embodiments, the compounds of Formulas I to XH, prodrugs, pharmaceutically acceptable salts, and pharmaceutically active metabolites and solvates thereof have an antipicornaviral activity, more preferably antirbino viral activity, corresponding to an EC 50 less than or equal to 100 μM in the Hl-HeLa cell culture assay. A "prodrug" is intended to mean a compound that is converted under physiological conditions or by solvolysis or metabolically to a specified compound that is pharmaceutically active. A prodrug may be a derivative of one ofthe compounds of this invention that contains a moiety, such as for example -CO 2 R, -PO(OR) 2 or -C=NR, that may be cleaved under physiological conditions or by solvolysis. Any suitable R substituent may be used that provides a pharmaceutically acceptable solvolysis or cleavage product. A prodrug containing such a moiety may be prepared according to conventional procedures by treatment of a compound of this invention containing, for example, an amido, carboxylic acid, or hydroxyl moiety with a suitable reagent. A "pharmaceutically active metabolite" is intended to mean a pharmacologically active compound produced through metabolism in the body of a specified compound. Prodrugs and active metabolites of compounds of this invention ofthe above-described Formulas may be determined using techniques known in the art, for example, through metabolic studies. See, e.g., "Design of Prodrugs," (Bundgaard, ed.), 1985, Elsevier Publishers B.V., Amsterdam, The Netherlands. A "pharmaceutically acceptable salt" is intended to mean a salt that retains the biological effectiveness ofthe free acids and bases of a specified compound and that is not biologically or otherwise undesirable. Examples of pharmaceutically acceptable salts include sulfates, pyrosulfates, bisulfates, sulfites, bisulfϊtes, phosphates, monohydrogenphosphates, dihydrogenphosphates, metaphosphates, pyrophosphates, chlorides, bromides, iodides, acetates, propionates, decanoates, caprylates, acrylates, formates, isobutyrates, caproates, heptanoates, propiolates, oxalates, malonates, succinates, suberates, sebacates, fumarates, maleates, butyne-l,4-dioates, hexyne-l,6-dioates, benzoates, chlorobenzoates, methylbenzoates, dinitrobenzoates, hydroxybenzoates, methoxybenzoates, phthalates, sulfonates, xylenesulfonates, phenylacetates, phenylpropionates, phenylbutyrates, citrates, lactates, γ-hydroxybutyrates, glycollates, tartrates, methane-sulfonates (mesylates), propanesulfonates, naphthalene- 1 -sulfonates, naphthalene-2-sulfonates, and mandelates. A "solvate" is intended to mean a pharmaceutically acceptable solvate form of a specified compound that retains the biological effectiveness of such compound. Examples of solvates include compounds ofthe invention in combination with water, isopropanol, ethanol, methanol, DMSO, ethyl acetate, acetic acid, or ethanolamine. In the case of compounds, salts, or solvates that are solids, it is understood by those skilled in the art that the inventive compounds, salts, and solvates may exist in different crystal forms, all of which are intended to be within the scope of the present invention and specified formulas. The present invention is also directed to a method of inhibiting picomaviral 3C protease activity, comprising contacting the protease with an effective amount of a compound of Formulas I to XH, or a pharmaceutically acceptable salt, prodrug, pharmaceutically active metabolite, or solvate thereof. For example, picomaviral 3C protease activity may be inhibited in mammalian tissue by administering a compound of Formulas I to XH or a pharmaceutically acceptable salt, prodrug, pharmaceutically active metabolite, or solvate thereof. More preferably, the present method is directed at inhibiting rhinoviral protease activity. "Treating" or "treatment" is intended to mean at least the mitigation of a disease condition in a mammal, such as a human, that is alleviated by the inhibition ofthe activity of one or more picomaviral 3C proteases, including, but not limited to human rhinoviruses, human poliovirus, human coxsackievimses, encephalomyocarditis virases, meningitis viras, and hepatitis A viras. The methods of treatment for mitigation of a disease condition include the use ofthe compounds in this invention in any conventionally acceptable manner, for example, as a prophylactic. The activity ofthe inventive compounds as inhibitors of picomaviral 3C protease activity may be measured by any ofthe suitable methods known to those skilled in the art, including in vivo and in vitro assays. An example of a suitable assay for activity measurements is the antiviral Hl-HeLa cell culture assay described herein. Administration ofthe compounds ofthe Formulas I to XH and their pharmaceutically acceptable prodrags, salts, active metabolites, and solvates may be performed according to any ofthe generally accepted modes of administration available to those skilled in the art. Illustrative examples of suitable modes of administration include oral, nasal, parenteral, topical, transdermal, and rectal. An inventive compound of Formulas I to XH or a pharmaceutically acceptable salt, prodrug, active metabolite, or solvate thereof may be administered as a pharmaceutical composition in any pharmaceutical form recognizable to the skilled artisan as being suitable. Suitable pharmaceutical forms include solid, semisolid, liquid, or lyophilized formulations, such as tablets, powders, capsules, suppositories, suspensions, liposomes, and aerosols. Pharmaceutical compositions ofthe invention may also include suitable excipients, diluents, vehicles, and carriers, as well as other pharmaceutically active agents, depending upon the intended use or mode of administration. In preferred embodiments, the inventive pharmaceutical compositions are delivered orally, or intranasally in the form of suspensions. Acceptable methods of preparing suitable pharmaceutical forms ofthe pharmaceutical compositions maybe routinely determined by those skilled in the art. For example, pharmaceutical preparations may be prepared following conventional techniques ofthe pharmaceutical chemist involving steps such as mixing, granulating, and compressing when necessary for tablet forms, or mixing, filling, and dissolving the ingredients as appropriate, to give the desired products for oral, parenteral, topical, intravaginal, intranasal, intrabronchial, intraocular, intraaural, and/or rectal administration. The compounds (active ingredients) may be formulated into solid oral dosage forms which may contain, but are not limited to, the following inactive ingredients: diluents (i.e., lactose, com starch, microcrystalline cellulose), binders (i.e., povidone, hydroxypropyl methylcellulose), disintegrants (i.e., crospovidone, croscarmellose sodium), lubricants (i.e., magnesium stearate, stearic acid), and colorants (FD&C lakes or dyes). Alternatively, the compounds may be formulated into other oral dosage forms including liquids, suspensions, emulsions, or soft gelatin capsules, with each dosage form having a unique set of ingredients. Solid or liquid pharmaceutically acceptable carriers, diluents, vehicles, or excipients may be employed in the pharmaceutical compositions. Illustrative solid carriers include starch, lactose, calcium sulfate dihydrate, terra alba, sucrose, talc, gelatin, pectin, acacia, magnesium stearate, and stearic acid. Hlustrative liquid carriers include syrup, peanut oil, olive oil, saline solution, and water. The carrier or diluent may include a suitable prolonged-release material, such as glyceryl monostearate or glyceryl distearate, alone or with a wax. When a liquid carrier is used, the preparation maybe in the form of a syrup, elixir, emulsion, soft gelatin capsule, sterile injectable liquid (e.g., solution), or a nonaqueous or aqueous liquid suspension. A dose ofthe pharmaceutical composition contains at least a therapeutically effective amount ofthe active compound (i.e., a compound of Formulas I to XH or a pharmaceutically acceptable salt, prodrug, active metabolite, or solvate thereof), and preferably is made up of one or more pharmaceutical dosage units. The selected dose maybe administered to a mammal, for example, a human patient, in need of treatment mediated by inhibition of picomaviral 3C protease activity, by any known or suitable method of administering the dose, including: topically, for example, as an ointment or cream; orally; rectally, for example, as a suppository; parenterally by injection; or continuously by intravaginal, intranasal, intrabronchial, intraaural, or intraocular infusion. A "therapeutically effective amount" is intended to mean the amount of an inventive agent that, when administered to a mammal in need thereof, is sufficient to effect treatment for disease conditions alleviated by the inhibition of the activity of one or more picomaviral 3C proteases, such as human rhinoviruses, human poliovirus, human coxsackievimses, encephalomyocarditis virases, menigoviras, and hepatitis A virus. The amount of a given compound ofthe invention that will be therapeutically effective will vary depending upon factors such as the particular compound, the disease condition and the severity thereof, the identity ofthe mammal in need thereof, which amount may be routinely determined by artisans. GENERAL SYNTHETICMETHODS Preferably, compounds ofthe general formulas are prepared by the methods of the present invention, including the General Methods below, where the R 1 , R 4 , R 5 , R 6 , Z and Z 1 substituents present in the compounds illustrated in the General and Specific Methods are as defined above. Abbreviations used herein include: DCC (1,3- dicyclohexylcarbodiimide), HOBT (1-hydroxybenzotriazole hydrate), HATU (O-(7- - tetramethyluromum hexafluorophosphate), IBX (2- iodoxybenzoic acid), FMOC (9-fluorenylmethoxycarbonyl), Boc (t-butoxycarbonyl), DIEA (diisopropylethylamme), DMSO (dimethylsulfoxide), TMSOTf (trimethylsilyl trifluoromethanesulfonate), TFA (trifluoroacetic acid), LiHMDS (lithium bis(trimethylsilyl)amide) . General Method 1 In General Method 1, a sidechain protected (P) compound 1 (Dragovich, et al., J. βcf. C7*em. 1998, 41, 2819), is coupled using standard peptide coupling methods, to another amino acid with a different protecting group (P') on the alpha-nitrogen, to give di-peptide compound 2. The P' protecting group is then selectively removed, and the resulting amine is coupled to a substituted pyrrole-2-carboxylic acid (prepared as described in General Methods 4, 5, and 6), or a suitably activated analog of this acid, such as an acid chloride, ester or amide (X 1 = OH, halo, etc.), to give 3. The sidechain- protecting group P is then removed to give 4. These compounds may also be made using solid phase synthetic techniques (Dragovich, et al., Bioorg. Med. Chem., 1999 7, 589), where protecting group P constitutes a linker (such as the Rink linker) attached to solid phase resin. General Method 2 In General Method 2, compound 5 (prepared by a method analogous to that described in Tian, et al., U.S. Provisional Patent Application No. 60/150,358, filed August 24, 1999 (now U.S. Patent Application No. 09/643,864) and also Baldwin et al., J. Org. Chem., 1971, 36, 1441) is coupled to another amino acid with sidechain protecting group P to give 6. The protecting group of 6 is removed, and the liberated amine is coupled to a 5-substituted pyrrole-2- carboxylic acid (prepared as described in General Methods 4, 5, and 6) via a suitably activated analog of this acid, such as an acid chloride, ester or amide (X 1 = OH, halo, etc.), to give compound 7. General Method 3 hi General Method 3, compound 5 is coupled to carboxylic acids ofthe type 8 (prepared as described in General Methods 7 and 8), where W = N or CH, to give compound 9. General Method 4 R 1 -M 10 11 12 In General Method 4, 2,5-disubstituted pyrroles are prepared by bromination of pyrrole-2-carboxylic acid ester 10, where R is an alkyl or aryl group, which is unsubstituted or substituted with one or more suitable substituents, to give 11, followed by a transition-metal mediated carbon-carbon bond forming reaction (for example, using Pd° with an appropriate ligand such as triphenylphosine or triphenylarsine) with an organometallic species, R ! M (for example, an organoboronic acid or an organotin compound) to give 12. General Method 5 phosgene equivalent 16 17 18 General Method 5 depicts another method used to make 2,5-disubstituted pyrroles, analogous to the method described by Kruse, et al., Heterocycles, 1987, 26, 3141. A carboxylic acid 13 is converted to a suitably activated species 14 (X 2 = a Weinreb amide (-N(OCH 3 )CH 3 ), halo, etc.) then reacted with a micleophilic organometallic compound containing a protected aldehyde to provide 15. The aldehyde is deprotected to give 16, then is condensed with an ammonia equivalent such as ammonium chloride, to provide pyrrole 17. This pyrrole is then reacted with a phosgene-type equivalent such as trichloroacetyl chloride (analogous to the method described by Bailey, et al., Org. Synth., 1971, 51, 100), to provide the 2,5-disubstituted pyrrole 18. (X 1 = OH, halo, etc.). General Method 6 General Method 6 shows an alternate method to make 2,5-disubstituted pyrroles. Aldehyde 19 is reacted with a micleophilic organometallic compound containing a protected aldehyde to provide alcohol 20. The alcohol is then oxidized to ketone 15 using standard methodology such as a Swem oxidation. Ketone 15 is carried on to pyrrole 18 using the same method as shown in General Method 5. General Method 7 21 22 23 26 27 General Method 7 depicts the preparation of a pyrrole containing the keto- methylene moiety, 27, analogous to the method described by Gonzalez-Muniz et. al. (Gonzalez-Muniz, et al., Tetrahedron, 1992, 48, 5191; Garcia-Lopez, et al., Tetrahedron Lett., 1988, 29, 1577; Garcia-Lopez, et al, Tetrahedron, 1988, 44, 5138). Carboxylic acid 21 is converted to a suitably reactive intermediate 22 such as a Weinreb amide, acid chloride or ester (X 2 = N(OCH 3 )CH 3 , halo, etc.) , then reacted with an organometallic reagent (R 4 M, such as methyllithium) to give pyrrole-acetone compound 23. This compound is then halogenated to give 24 (where X 3 = halo), then reacted with a malonate salt (R ' = alkyl) to give 25. This compound is deprotonated by treatment with a strong base, then reacted with an electrophile (R 5 -X 3 ) to give 26. Decarboxylation of compound 26 gives product 27. General Method 8 31 32 33 General Method 8 shows the preparation of an optically active pyrrole containing the keto-methylene moiety, compound 33. Carboxylic acid 28 is converted to chiral amide 29, by coupling to a chiral amine or oxazolidinone, N c , that is known to control enolate alkylation diastereoselectivity. Compound 29 is deprotonated, then reacted with an electrophile such as t-butyl bromoacetate, analogous to the method described by Charlton, et al., Can. J. Chem. 1997, 75, 1076, to give 30. The chiral auxiliary is removed, and the resulting acid is esterified to give 31. The R' ester of 31 is selectively removed, and the resulting acid is converted to the disubstituted amide 32, by coupling to a secondary amine. Compound 32 is reacted with pyrrole 17, under typical Vilsmeier reaction conditions (Silverstein, et al., Org. Synth., 1963, Coll. Vol. IV, 831) to give pyrrole 33. As used herein, R 1 , R" and R" are each independently lower alkyl, which is unsubstituted or substituted with one or more suitable substituents, . General Method 9 36 37 In General Method 9, a pyrrole-carboxylic acid 34 (commercially available or prepared by methods described in the chemical literature or as prepared as described in General Methods 4, 5 and 6), where R 1 is as defined above, is transformed into ketoester 35. Compound 35 is subsequently deprotonated and coupled with triflate 37 (wliich incorporates R 5 and which can be prepared from hydroxy-ester 36, where R"" is alkyl or cycloaUcyl, e.g., lower alkyl, allyl, benzyl, or C 3 -C 6 cycloaUcyl, which are unsubstituted or substituted with one or more suitable substituents) to afford intermediate 38 after acid-effected decarboxylation. Intermediates 8 is related to compound 32 (General Method 8) and maybe utilized in any ofthe previously described general syntheses where appropriate. Note that the NH present in pyrrole-carboxylic acid 34 may also be protected with a suitable protecting group which may be removed at any time during the synthesis of 38. The methodology for converting pyrrole-carboxylic acid 34 to intermediate 38 is generally described in: Hoffman, R. V.; Tao, J. Tetrahedron 1991, 53, 7119-7126. General Method 10 39 40 41 In General Method 10, an amino acid 39 (or salt thereof) which incorporates R 5 is transformed into hydroxy acid 40. This intermediate is subsequently converted to hydroxy ester 41 which may be utilized in General Method 9 above for the preparation ofthe compounds described in this invention. SPECIFIC METHODS Specific Method 1 42 43 47 48 Specific Method 1 describes the preparation of compounds containing a glutamine residue in the P-1 position. FMOC-4-amino-hept-2(trans)-enedioic acid -1 ethyl ester 42 (Dragovich, et al., J Med. Chem. 1998, 41, 2819) was coupled to Rink polystyrene utilizing HATU as a coupling reagent to get 43. The FMOC protecting group was removed with piperidine, and the liberated amine was then coupled to an FMOC-protected amino acid 44 to get compound 45. The FMOC of 45 was again removed with piperidine, and the free amine was acylated with a 5-substituted-2- pyrrole carboxylic acid chloride 46 (prepared as described in Specific Methods 4,5, and 6). The final compound, 37, was cleaved from the resin with trifluoroacetic acid, to give compound 48. Specific Method 2 1) HCI Specific Method 2 describes the synthesis of compounds containing the oxo- pyrrolidine sidechain in the P-1 position. Boc-protected 4S-amino-5-(2-oxo-pyrrolidin- 3S-yl)-pent-2(trans)-enoic acid ethyl ester 49 (prepared by a method analogous to that described in Tian, et al., U.S. Provisional Patent Application No. 60/150,358, filed August 24, 1999 and also Baldwin et al., J. Org. Chem., 1971, 36, 1441) was deprotected with HCl, then coupled using HATU to a Boc-protected amino acid 50. The Boc -protected product 51 was treated with HCl, then coupled to a 5-substituted- pyrrole-2-carboxylic acid chloride 46 (prepared as described in Specific Methods 4, 5, and 6), to produce product 52. Specific Method 3 1) HCI Specific Method 3 describes the preparation of compounds containing the pyrrole-ketomethylene moiety. Boc-protected 4S-amino-5-(2-oxo-pyrrolidin-3S-yι)- pent-2(trans)-enoic acid ethyl ester 49 was deprotected with HCl, then coupled to acid 53 (prepared as described in Specific Method 7 and 8), using HATU, to provide compound 54. Specific Method 4 1) LiOH j R OMe 2) oxalyl chloride N /I Cl H H 58 46 Specific Method 4 describes the synthesis of 5-substituted-pyrrole-2-carboxylic acid chlorides. Pyrrole-2-carboxylic acid 55 was esterified with diazomethane, to give methyl ester 56, then brominated with N-bromosuccinimide to give 5-bromopyrrole 57. The bromide was reacted with a boronic acid using standard Suzuki coupling conditions to give 58. The methyl ester was cleaved with lithium hydroxide, and the resulting acid was converted to the acid chloride 46 using oxalyl chloride. Specific Method 5 46 Specific Method 5 describes an alternate method of pyrrole synthesis. Carboxylic acid 59 was converted to an acid chloride using oxalyl chloride, then converted to the N-methoxy-N-methyl amide with O,N-dimethyl hydroxylamine. This amide 60 was reacted with Grignard reagent 61 to give ketone 62. The dioxolane- protecting group was converted to the corresponding aldehyde with aqueous HCl, then condensed with ammonium chloride to give pyrrole 63. This pyrrole was reacted with trichloroacetyl chloride to give the disubstituted pyrrole 64, which was then hydrodrolyzed to the corresponding carboxylic acid with lithium hydroxide, then converted to the acid chloride 46 using oxalyl chloride. Specific Method 6 Specific Method 6 describes an alternate method of pyrrole synthesis. Aldehyde 65 was reacted with Grignard reagent 61 to give alcohol 66. This alcohol was subjected to Swem oxidation conditions to provide ketone 62, which was converted to the acid chloride 46 according to Specific Method 5. Specific Method 7 69 70 Specific Method 7 describes the synthesis of a racemic pyrrole-ketomethylene compound. 5-Substituted-pyrrole-2-carboxylic acid 67 (prepared as described in Specific Methods 4, 5 and 6) was converted to the Weinreb amide 68 using standard conditions, then treated with methyllithium to give pyrrole-acetone 69. This ketone was converted to its silyl-enol ether with trimethylsilyl inflate, then brorninated with N- bromosuccinimide to give bromide 70. The bromide was displaced with sodium diethylmalonate to give malonate 71. The sodium enolate of this compound was alkylated to give 72, which was then de-esterified and de-carboxylated to give carboxylic acid 53. Specific Method 8 1) pivaloyl chloride Et 3 N 77 78 79 Specific Method 8 describes the enantioselective preparation of a pyrrole- ketomethylene compound. Carboxylic acid 73 was converted to the chiral amide 74 using standard conditions, then converted to its lithium enolate and alkylated with t- butylbromoacetate to give 75. The chiral auxiliary was removed with lithium hydroperoxide, and the resulting acid was esterified with diazomethane to give ester 76. The t-butylester was selectively removed with trifluoroacetic acid, and the resulting acid was converted to dimethyl amide 77 by treatment ofthe acid chloride (formed using oxalyl chloride) with dimethylamine hydrochloride. Amide 77 was reacted with pyrrole 63 (prepared as described in Specific Methods 4,5 and 6) using standard Nilsmeier conditions to give pyrrole-ketomethylene 78. The methyl ester was cleaved with lithium hydroxide to give carboxylic acid 79. Specific Method 9 95% 80 81 82 In Specific Method 9, H-D-propargyl glycine (80) (or a suitable salt thereof) is treated with sodium nitrite under mildly acidic aqueous conditions to provide hydroxy acid 81 in good yield. This material is esterified by exposure to acidic methanol to give hydroxy ester 82. Specific Method 10 83 84 85 4M HCI-dioxane ROH, rt 55-86% from 84 86 R = Me 87 R = Bn In Specific Method 10, Boc-D-3,4-difluorophenylalanine 83 is deprotected by treatment with trifluoroacetic acid in CH 2 C1 2 to afford amino acid TFA salt 84. This intermediate is treated with sodium nitrite under mildly acidic aqueous conditions to provide hydroxy acid 85 in good yield. Compound 85 is esterified by exposure to either methanol or benzyl alcohol under acidic conditions to give hydroxy esters 86 and 87, respectively. Specific Method 11 88 89 In Specific Method 11, 2-ketobutyric acid (88) is subjected to an enzyme-mediated reduction process to afford hydroxy acid 89 in good yield. EXAMPLES Examples ofthe processes used to make several ofthe compounds of Formulas I and II are set forth below. The structures ofthe compounds ofthe following examples were confirmed by one or more ofthe following: proton magnetic resonance spectroscopy, infrared spectroscopy, elemental microanalysis and melting point. Proton magnetic resonance (*H NMR) spectra were determined using either a Narian UNITYplus 300 or a General Electric QE-300 spectrometer operating at a field strength of 300 megahertz (MHz). Chemical shifts are reported in parts per million (ppm, δ) downfield from an internal tetramethylsilane standard. Alternatively, H NMR spectra were referenced to residual protic solvent signals as follows: CHCI3 = 7.26 ppm; DMSO = 2.49 ppm, C6HD5 = 7.15 ppm. Peak multiplicities are designated as follows: s, singlet; d, doublet; dd, doublet of doublets; t, triplet; q, quartet; br, broad resonance; m, multiplet. Coupling constants are given in Hertz. Infrared absoφtion (IR) spectra were obtained using a Perkin-Elmer 1600 series FTIR spectrometer. Elemental microanalyses were performed by Atlantic Microlab ie, Norcross, GA and gave results for the elements stated within ±0.4% ofthe theoretical values. Flash column chromatography was conducted using Silica gel 60 (Merck Art 9385). Analytical thin layer chromatography (TLC) was conducted using precoated sheets of Silica 60 F254 (Merck Art 5719). Melting points were determined on a Mel-Temp apparatus and are uncorrected. All reactions were conducted in septum-sealed flasks under a slight positive pressure of argon unless otherwise noted. All commercial reagents were used as received from their respective suppliers with the following exceptions. Tetrahydrofuran (THF) was distilled from sodium-benzophenone ketyl prior to use. Dichloromethane (CH2CI2) was distilled from calcium hydride prior to use. The abbreviations used herein include: Et2θ (diethyl ether), DMF (N,N-dimethylformamide), DMSO (dimethylsulfoxide), MTBE (tert-butyl methyl ether), CH3OH (methanol), EtOH (ethanol), EtOAc (ethyl acetate), DME (ethylene glycol dimethyl ether) Ac (acetyl), Me (methyl), Ph (phenyl), Tr (triphenylmethyl), Cbz (benzyloxycarbonyl), Boc (tert-butoxycarbonyl), TFA (trifluoroacetic acid), DIEA (N,N-diisopropylethylamine), TMEDA (N,N,N^N'-teframethylethylenediamine), AcOH (acetic acid), Ac2θ (acetic anhydride), NMM (4-methylmorpholine), HOBt (1-hydroxybenzotriazole hydrate), HATU (O-(7-azabenzotriazol-l-yl)-N,N,N',N l - tetramethyluronium hexafluorophosphate), EDC (l-(3-dimethylaminopropyl)- 3-ethylcarbarbodiimide hydrochloride), DCC (dicyclohexyl-carbodiimide), DDQ (2,3-dichloro-5,6-dicyano-l,4-benzoquinone), DMAP (4-dimethylaminopyridine), Gin (glutamine), Leu (leucine), Phe (phenylalanine), Phe(4-F) (4-fluorophenylalanine), Val (valine), amino-Ala (2,3-diaminopropionic acid), and (S)-Pyrrol-Ala((2S,3'S)- 2-amino-3-(2'-oxopyrrolidin-3'-yl)-propionic acid). Additionally, "L" represents the configuration of naturally occurring amino acids. EXAMPLE 1 Preparation of Gln-resin and Phe-Gln resin Fmoc-Rink polystyrene resin (1.58 mmol, 2.40 g) was treated with a 1:1 solution of DMF-piperidine (25 ml) in a shaker vessel, to remove the Fmoc. The resulting slurry was agitated for 15 min, then washed with DMF (3x10 ml). The resin was then treated with a solution of Fmoc-4-amino-hept-2(trans)-enedioic acid- 1 -ethyl ester la - b (2.37 mmol, 1.00 g), DIEA (4.74 mmol, 0.82 ml), and HATU (2.37 mmol, 0.90 g) in DMF (25 ml). The resulting mixture was agitated for 1 h, then washed with DMF (3x10 ml). The Fmoc was then removed by treatment with a solution of 20% piperidine-DMF (25 ml), and agitation for 10 min. The resulting resin was washed with DMF (3x10 ml), MeOH (3x10 ml), and CH 2 C1 2 (3x10 ml). (The resin at this stage will be hereafter referred to as Gln-resin) The Gln-resin was then treated with a solution of Fmoc-phenylalanine (4.74 mmol, 1.84 g), DIEA (9.48 mmol, 1.65 ml), and HATU (4.74 mmol, 1.80 g) in DMF (25 ml). The resulting mixture was agitated for 1 h, then washed with DMF (3x25 ml). The Fmoc was removed by treatment with a solution of 20% piperidine-DMF (25 ml), then agitation for 10 min. The resin was washed with DMF (3x10 ml), MeOH (3x10 ml), and CH 2 C1 2 (3x10 ml). The resin was then dried in a vacuum desiccator. (The resin at this stage will be hereafter referred to as Phe-Gln-resin) . EXAMPLE 2 6-Carbamoyl-4S-{2S-[(5-naphthalen-l-yl-lH-pyrrole-2-carbonyl)-amino-3-phenyl- propionylamino}-hex-2(trans)-enoic acid ethyl ester. (Compound 3) 5-Naphthalen-l-yl-lH-pyrrole-2-carboxylic acid chloride Method 4 General Experimental: Pyrrole-2-carboxylic acid (90.0 mmol, 10.0 g) in diethyl ether (200 ml) was treated with diazomethane (270 mmol, generated from N- nitroso-N-methyl urea), then back titrated with acetic acid until the yellow color dissipated. The solution was washed with saturated aqueous sodium bicarbonate (3x20 ml) and brine (3x20 ml), then concentrated under reduced pressure to provide 10 g (88%) of pyrrole-2-carboxylic acid methyl ester. Η NMR (CDC1 3 ) δ 9.14 (1H, s), 6.98-6.65 (1H, m), 6.94-6.91 (1H, m), 6.29-6.26 (1H, m), 3.86 (3H, s). A solution of pyrrole-2-carboxylic acid methyl ester (79.9 mmol, 10.0 g) in carbon tetrachloride (300 ml) was heated to 70 °C, then treated dropwise with a solution of bromine (99.9 mmol, 126.0 ml) in carbon tetrachloride (200 ml). The reaction was initiated by the addition of iodine (40 mg). After the addition was complete, the reaction was held at 70 °C for 10 min, then cooled to room temperature using an ice bath. The mixture was washed with 10% aqueous sodium carbonate (100 ml), followed by water (100 ml). The organics were concentrated under reduced pressure and the residue was purified by silica gel chromatography to provide 4.5 g (27%) of 5-bromo-lH-ρyrrole-2-carboxylic acid methyl ester. ! H NMR (CDC1 3 ) δ 9.29 (1H, s), 6.80 (1H, dd, J = 3.9, 2.7), 6.23 (1H, dd, J = 3.8, 2.6), 3.88 (3H, s). Argon gas was bubbled 15 min through a solution of 5-bromo-lH-pyrrole-2- carboxylic acid methyl ester (10.0 mmol, 2.04 g), 1-naphthylboronic acid (30.0 mmol, 5.16 g), 2M aqueous sodium carbonate (20 ml), and DMF (150 ml). The mixture was then treated with tris(dibenzylidienacetone)dipalladium (0) (0.50 mmol, 0.46 g), and triphenylarsine (2.0 mmol, 0.61 g), then heated to reflux under argon for 12 h. The mixture was partitioned between ethyl acetate (500 ml) and water (150 ml). The organics were filtered through celite, washed with brine (3x50 ml), then concentrated under reduced pressure and the residue was purified by silica gel chromatography to provide 2.05 g (81%) of 5-naphthalen-l-yl-lH-pyrrole-2-carboxylic acid methyl ester. Η NMR (CDC1 3 ) δ 9.37 (1H, s), 8.22-8.17 (1H, m), 8.16-7.89 (2H, m), 7.59-7.50 (4H, m), 7.88 (1H, dd, J = 3.9, 2.7), 6.22 (1H, dd, J = 3.8. 2.6), 3.88 (3H, s). 5-Naphthalen-l-yl-lH-pyrrole-2-carboxylic acid methyl ester was diluted with 1:1 dioxane-water (30 ml), and treated with lithium hydroxide hydrate (24.4 mmol, 1.02 g), then heated to reflux for 15 min. The solution was acidified with 20% aqueous citric acid (30 ml), then extracted with ethyl acetate (75 ml). The organics were washed with brine (2x20 ml), then concentrated under reduced pressure. The residue was diluted with CH 2 C1 2 , (30 ml), and treated with oxalyl chloride (24.0 mmol, 2.10 ml), and DMF (one drop), then heated to reflux for 30 min. The solution was concentrated under reduced pressure to provide 1.95 g of 5-naphthalen-l-yl-lH-pyrrole-2-carboxylic acid chloride. Method 1 General Experimental: 5-Naphthalen-l-yl-lH-pyrrole-2-carboxylic acid chloride (0.75 mmol, 0.19 g, prepared as described above) in CH 2 C1 2 (10 ml) and collidine (3.75 mmol, 0.50 ml) was added to Phe-Gln-resin, prepared as described in Example 1,(0.38 mmol, 0.51 g), and agitated for 1 h. The resin was then washed with CH 2 C1 2 (3x10 ml), then suspended in a solution of 95:5 TFA-CH 2 C1 2 (10 ml) and stirred vigorously. The resin was separated by filtration, and the filtrate was concentrated under reduced pressure. The resulting oil was purified by preparative reverse phase chromatography (H 2 O-CH 3 CN gradient) to provide 21 mg (10 %) ofthe title product. Η NMR (CDC1 3 ) δ 10.55 (IH, br s), 8.16-8.08 (IH, m), 7.83-7.73 (2H, m), 7.48-7.36 (4H, m), 7.27-7.11 (5H, m), 6.88 (IH, dd, J = 3.7, 2.5), 6.54 (IH, dd, J = 15.7, 5.4), 6.41 (IH, dd, J = 3.7, 2.5), 5.46 (IH, dd, J = 15.7, 1.6), 4.62 (IH, t, J = 7.2), 4.45-4.35 (IH, m), 4.09 (2H, q, J = 7.2), 3.05-2.99 (2H, m), 2.19-2.11 (2H, m), 1.92- 1.80 (IH, m), 1.68-1.54 (IH, m), 1.21 (3H, t, J = 7.2). HRMS (FAB) 589.2427 (MNa + , calcd. 589.2447). EXAMPLE 3 6-Carbamoyl-4S-(2S-{[5-(2,3-dichloro-phenyl)-lH-pyrrole-2-carbonyl]-amino}-3- phenyl-proρionylamino-hex-2(trans)-enoic acid ethyl ester. (Compound 1) 5-(2,3-Dichloro-phenyl)-lH-pyrrole-2-carboxylic acid chloride was prepared according to the procedure described in Method 4 of Example 2, starting with 2,3-dichlorophenyl boronic acid. This material was coupled to Phe-Gln resin and converted to the title compound according to the procedure described in Method 1 of Example 2. Η NMR (CD 3 OD) δ 7.52-7.44 (2H, m), 7.36-7.16 (6H, m), 6.83 (IH, d, J = 3.9), 6.64 (IH, dd, J = 15.8, 5.7), 6.54 (IH, d, J = 3.9), 5.57 (IH, d, J = 6.0), 4.68 (IH, t, J = 7.7), 4.53-4.42 (IH, m), 4.17 (2H, q, J = 7.1), 3.19-3.03 (2H, m), 2.28 (2H, t, J = 7.9), 1.99-1.85 (IH, m), 1.78-1.65 (IH, m), 1.28 (3H, t, J = 7.1). HRMS (MALDI) 607.1501 (MNa + , calcd. 607.1491). EXAMPLE 4 6-Carbamoyl-4S-{3-phenyl-2S-[(5-(2-trifluoromethyl-phenyl)-lH-pyrrole-2-carbonyl)- amino]-propionylamino}-hex-2(trans)-enoic acid ethyl ester. (Compound 2) 5-(2-Trifluoromethyl-phenyl)-lH-pyrrole-2-carboxylic acid chloride. Method 6 General Experimental: Magnesium (230.0 mmol, 5.6 g) in THF (200 ml), under an argon atmosphere, was treated with 2-(2-bromoethyl)-l,3-dioxolane (200.0 mmol, 23.5 ml), slowly, keeping the internal temperature below 35 °C with the aid of an ice bath. After completion of the addition, the mixture was held at room temperature for an additional 1 h. 2-Trifluoromethyl benzaldehyde (100 mmol, 13.2 ml) in THF (100 ml) was cooled to -78 °C under an argon atmosphere, then treated with the freshly formed Grignard reagent prepared above. After completion of the addition, the solution was allowed to warm to room temperature, then held at room temperature overnight. The reaction mixture was then poured into saturated aqueous NH 4 C1 (200 ml), and extracted with ethyl acetate (2x150 ml). The combined organics were washed with brine (2x75 ml), then concentrated under reduced pressure to give 32.8 g of 3-[l,3]dioxolan-2-yl-l-(2-trifluoromethyl-phenyl)-propan-l-ol, which may be used without further purification. Η NMR (CDC1 3 ) δ 7.78 (IH, d, J = 7.7), 7.62-7.52 (2H, m), 7.34 (IH, t, J = 7.6), 4.92 (IH, t, J = 4.0), 4.00-3.81 (5H, ), 1.90-1.80 (4H, m). Oxalyl chloride (115.0 mmol, 10.0 ml) in CH 2 C1 2 (200 ml) was cooled to -78 °C under an argon atmosphere. DMSO (240.0 mmol, 17.0 ml) was then added slowly, keeping the internal temperature below -50 °C. After completing the addition, the solution was held 20 minutes at -78 °C. 3-[l,3]Dioxolan-2-yl-l-(2-trifluoromethyl- phenyl)-propan-l-ol (32.8 g of crade material prepared above) in CH 2 C1 2 (30 ml) was added slowly, keeping the internal temperature below -50 °C. The mixture was held at -78 °C for 30 minutes, then treated with Et 3 N (480 mmol, 70.0 ml). The mixture was allowed to warm to room temperature, then washed with water (2x75 ml), then concentrated under reduced pressure to give crude 3-[l,3]dioxolan-2-yl-l-(2- trifluoromethyl-phenyl)-propan-l-one, which may be used without further purification. Η NMR (CDC1 3 ) δ 7.00 (IH, d, J = 7.7), 7.63-7.50 (2H, m), 7.44 (IH, d, J = 7.4), 4.99 (IH, t, J = 4.3), 3.97-3.82 (4H, m), 2.98 (2H, t, J = 7.3) 2.12 (2H, dt, J = 7.4, 4.3). The crade product 3-[l,3]dioxolan-2-yl-l-(2-trifluoromethyl-phenyl)-propan-l- one, in its entirety, was treated with 1:1 2N HCl : dioxane (150 ml), then heated to reflux for 20 minutes. The resulting mixture was extracted with ethyl acetate (2x150 ml). The combined organics were washed with brine (2x75 ml), then concentrated under reduced pressure to give crude 4-oxo-4-(2-trifluoromethyl-phenyl)- butyrylaldehyde, which may be used without further purification. Η NMR (CDC1 3 ) δ 9.89 (IH, s), 7.71 (IH, d, J = 7.5), 7.66-7.52 (3H, m), 3.15 (2H, t, J = 6.1), 3.01-2.92 (2H, m). The above prepared 4-oxo-4-(2-trifluoromethyl-phenyl)-butyrylaldehyde was diluted with ethanol (300 ml), and treated with arnmonium acetate (1.00 mol, 53.5 g), then heated to reflux for 1 h. This mixture was diluted with ethyl acetate (500 ml) and washed with brine (2x75 ml). The organics were concentrated under reduced pressure and the residue was purified by silica gel chromatography to provide 7.8 g (37% from 2-trifluoromethyl benzaldehyde) of 2-(2-trifluoromethyl-phenyl)-lH-pyrrole. ! H NMR (CDC1 3 ) δ 8.51 (IH, br s), 7.74 (IH, d, J = 7.9), 7.60-7.54 (2H, m), 7.44-7.36 (IH, m), 6.95-6.91 (IH, m), 6.44-6.41 (IH, m), 6.33 (IH, dd, J = 6.0, 2.6). This material was treated with trichloroacetyl chloride, hydrolyzed with lithium hydroxide, and converted to the corresponding acid chloride using oxalyl chloride, as described in Method 5 of Example 12, to give 5-(2-trifluoromethyl-phenyl)-lH-pyrrole- 2-carboxylic acid chloride. Η NMR (CDC1 3 ) δ 9.35 (IH, s), 7.80 (IH, d, J = 7.4), 7.68-7.52 (3H,m), 7.26-7.23 (IH, m), 7.53-7.49 (IH, m). 5-(2-Trifluoromethyl-phenyl)-lH-pyrrole-2-carboxylic acid chloride was coupled to Phe-Gln-resin, and converted to the title compound according to the procedure described in Method 1 of Example 2. Η NMR (CDC1 3 ) δ 10.10 (IH, br s), 7.21 (IH, d, J = 7.8), 7.59-7.40 (3H, m), 7.32-7.16 (5H, m), 6.82-6.76 (IH, m), 6.61 (IH, dd, J = 15.8, 5.2), 6.39-6.33 (IH, m), 5.55 (IH, d, J = 15.7), 4.69 (IH, t, J = 7.2), 4.54-4.43 (IH, m), 4.16 (2H, q, J = 7.1), 3.09 (2H, d, J = 7.0), 2.25-2.15 (2H, m), 2.20- 1.85 (IH, m), 1.78-1.52 (IH, m), 1.27 (3H, t, J = 7.1). HRMS (FAB) 607.2128 (MNa + calcd. 607.2144). EXAMPLE 5 6-Carbamoyl-4S-(2S-{[5-(5-chloro-2-methoxy-phenyl)-lH-pyrrole-2-carbonyl]- amino}-3-phenyl-propionylamino)-hex-2(trans)-enoic acid ethyl ester. (Compound 4) 5-(5-Chloro-2-methoxy-phenyl)-lH-pyrrole-2-carboxylic acid chloride was prepared according to the procedure described in Method 4 of Example 2, starting with 5-chloro-2-methoxyphenyl boronic acid. This material was coupled to Phe-Gln resin, and converted to the title compound according to the procedure described in Method 1 of Example 2. Η NMR (CDC1 3 ) δ 10.50 (IH, br s), 7.56 (IH, d, J = 2.6), 7.30-7.12 (6H, m), 6.88 (IH, d, J = 8.9), 6.79-6.75 (IH, m), 6.60 (IH, dd, J = 15.7, 5.3), 6.58-6.55 (IH, m), 5.54 (IH, dd, J = 15.7, 1.5), 4.73-4.65 (IH, m), 4.53-4.43 (IH, m), 4.16 (2H, q, J = 7.1), 3.93 (3H, s,), 3.14-3.04 (2H, m), 2.23-2.15 (2H, m), 1.99-1.84 (IH, m), 1.78-1.62 (IH, m), 1.27 (3H, t, J = 7.1). HRMS (FAB) 603.1963 (MNa + , calc. 603.1986). EXAMPLE 6 6-Carbamoyl-4S-{2S-[(5-isoquinolin-4-yl-lH-pyrrole-2-carbonyl)-amino]-3-phenyl- propionylamino}-hex-2(trans)-enoic acid ethyl ester. (Compound 5) 4-Bromoisoquinoline (4.10 mmol, 0.85 g) in toluene (15 ml) was treated with hexamethylditin (5.6 mmol, 2.00 g), and tefraMs( phenylphosphine)-palladium(0) (0.20 mmol, 0.24 g), then heated to reflux overnight under an argon atmosphere. The resulting mixture was concentrated under reduced pressure, then purified by silica gel chromatography to provide 1.03 g (87%) of 4-(trimethylstannyl)-isoquinoline. H NMR (CDC1 3 ) δ 9.23 (IH, s), 8.52 (IH, s), 8.00 (IH, d, J = 8.1), 7.78-7.62 (3H, m), 0.5 (9H, s). 5-Bromo-lH-pyrrole-2-carboxylic acid methyl ester (1.49 mmol, 0.30 g, prepared according to the procedure described in Method 4 of Example 2) in NMP (10 ml) was treated with triphenylarsine (0.30 mmol, 91 mg), tris(dibenzylideneacetone) dipalladium(O) (0.07 mmol, 68 mg), and 4- (trimethylstannyl)-isoquinoline (2.22 mmol, 0.65 g), then heated to reflux under an argon atmosphere overnight. The resulting mixture was concentrated under reduced pressure, then purified by silica gel chromatography to provide 0.21 g (55%) of 5- isoquinolin-4-yl-lH-pyrrole-2-carboxylic acid methyl ester. ! H NMR (CDC1 3 ) δ 9.81 (IH, br s), 9.35 (IH, s), 8.66 (IH, s), 8.31 (IH, d, J = 8.5), 8.10 (IH, d, J = 8.1), 7.91 (IH, t, J = 15.2), 7.79 (IH, t, J = 15.2), 7.11 (IH, dd, J = 3.8, 2.5), 6.64 (IH, dd, J = 3.7, 2.7), 3.90 (3H, s). This material was converted to 5-isoquinolin-4-yl-lH-pyrrole-2-carboxylic acid chloride according to the procedures described in Method 4 of Example 2. This material was then coupled to Phe-Gln resin, and converted to the title compound according to the procedure of Method 1 of Example 2. ! H NMR (CD 3 OD) δ 9.20 (IH, br s), 8.51 (IH, s), 8.27 (IH, d, J = 8.6), 8.17 (IH, d, J = 8.1), 7.85 (IH, t, J = 8.4), 7.74 (IH, t, J = 8.2), 7.30-7.17 (9H, m), 7.07 (IH, d, J = 3.8), 6.65 (IH, dd, J = 15.8, 5.6), 6.56 (IH, d, J = 3.8), 5.58 (IH, d, J = 15.8), 4.55-4.46 (IH, m), 4.18 (2H, q, J = 7.1), 3.17 (2H, t, J = 7.8), 2.29 (2H, q, J = 7.9), 2.24-1.68 (4H, m), 1.31 (3H, t, J = 7.1). HRMS (FAB) 590.2363 (MNa + , calcd. 590.2379). EXAMPLE 7 6-Carbamoyl-4S-(2S-{[5-(3-isopropyl-phenyl)-lH-pyrrole-2-carbonyl]-amino}-3- phenyl-propionylamino)-hex-2(trans)-enoic acid ethyl ester. (Compound 6) 5-(3-iso-Propyl-phenyl)-lH-pyrrole-2-carboxylic acid chloride was prepared according to the procedure described in Method 4 of Example 2, starting with 3- isopropylphenyl boronic acid. This product was coupled to Phe-Gln resin, according to the procedure described in Method 1 of Example 2. Η NMR (CD 3 OD) δ 11.13 (IH, br s), 7.53 (IH, s), 7.47 (IH, d, J = 7.9), 7.32-7.26 (5H, m), 7.25-7.18 (IH, m), 7.14 (IH, d, J = 7.8), 6.93 (IH, dd, J = 3.7, 2.3), 6.65 (IH, dd, J = 15.7, 5.6), 6.53 (IH, dd, J = 3.8, 2.4), 5.58 (IH, dd, J = 15.7, 1.5), 4.71 (IH, t, J = 7.7), 4.53-4.44 (IH, m), 4.18 (2H, q, J = 7.1), 3.20-3.06 (2H, m), 2.94 (IH, d, J = 6.9), 2.30 (2H, t, J = 7.2), 2.00-1.87 (IH, m), 1.80-1.66 (IH, m), 1.29 (3H, t, J = 7.0), 1.28 (6H, d, J = 7.0). HRMS (FAB) 581.2761 (MNa + , calcd. 581.2740). Anal. (C 32 H 38 N 4 O 5 . 0.7 H 2 O) C, H, N. EXAMPLE 8 6-Carbamoyl-4S-(2S-{[5-(2,5-dimethoxy-phenyl)-lH-pyrrole-2-carbonyl]-amino}-3- phenyl-propionylamino)-hex-2-enoic acid ethyl ester. (Compound 7) 5-(2,5-Dimethoxy-phenyl)-lH-pyrrole-2-carboxylic acid chloride was prepared according to the procedure described in Method 4 of Example 2, starting with 2,5- dimethoxyphenyl boronic acid. This material was coupled to Phe-Gln resin, and converted to the title compound according to the procedure described in Method 1 of Example 2. Η NMR (CDC1 3 ) δ 10.55 (IH, br s), 7.37-7.20 (7H, m), 6.90 (IH, d, J = 9.0), 6.81 (IH, d, J = 3.0), 6.65 (IH, dd, J = 15.7, 5.3), 6.63-6.57 (IH, m), 5.61 (IH, dd, J = 15.7, 1.5), 4.73-4.65 (IH, m), 4.53-4.43 (IH, m), 4.16 (2H, q, J = 7.1), 3.89 (3H, s), 3.80 (3H, s), 3.14-3.04 (2H, m), 2.35-2.20 (2H, m), 2.10-1.85 (IH, m), 1.80-1.70 (IH, m), 1.27 (3H, t, J = 7.1). HRMS (FAB) 599.2499 (MNa + , calcd. 599.2482). EXAMPLE 9 6-Carbamoyl-4S-{3-phenyl-2S-[(5-o-tolyl-lH-pyrrole-2-carbonyl)-amino]- propionylamino}-hex-2(trans)-enoic acid ethyl ester. (Compound 9) 5-(o-Tolyl)-lH-pyrrole-2-carboxylic acid chloride was prepared according to the procedure described in Method 4 of Example 2, starting with o-tolyl boronic acid. This material was coupled to Phe-Gln resin, and converted to the title compound according to the procedure described in Method 1 of Example 2. Η NMR (CDC1 3 ) δ 10.10 (IH, br s), 7.38-7.15 (7H, m), 6.81 (IH, d, J = 7.2), 6.77-6.70 (IH, m), 6.65-6.55 (2H, m), 6.29 (IH, s), 5.58 (IH, d, J = 15.5), 4.76-4.65 (IH, m), 4.58-4.45 (IH, m), 4.18 (2H, q, J = 7.1), 3.20-3.03 (2H, m), 2.20-2.00 (5H, m), 1.93-1.77 (IH, m), 1.72-1.57 (IH, m), 1.90 (3H, t, J = 7.1). HRMS (FAB) 553.2438 (MNa + , calcd. 553.2427). Anal. (C 30 H 34 N 4 O 5 • 1.0 H 2 O) C, H, N. EXAMPLE 10 6-Carbamoyl-4S-{3-phenyl-2S-[(5-phenyl-lH-pyιτole-2-carbonyl)-amino]- propionylamino}-hex-2(trans)-enoic acid ethyl ester. (Compound 10) 5 -Phenyl- lH-pyrrole-2-carboxylic acid chloride was prepared according to the procedure described in Method 4 of Example 2, starting with phenyl boronic acid. This material was coupled to Phe-Gln resin, and converted to the title compound according to the procedure described in Method 1 of Example 2. Η NMR (CDC1 3 ) δ 11.15 (IH, br s), 8.27 (IH, d, J =4.8), 7.67 (2H, d, J = 7.3), 7.39 (2H, t, J = 7.8), 7.33-7.19 (5H, m), 7.76-7.71 (IH, ), 6.66 (IH, dd, J = 15.7, 5.7), 6.57-6.53 (IH, m), 5.59 (IH, d, J - 15.7), 4.71 (IH, t, J = 7.6), 4.55-4.45 (IH, m), 4.19 (2H, q, J = 7.2), 3.33 (2H, q, J = 8.3), 2.30 (2H, t, J = 7.3), 2.03-1.87 (IH, m), 1.80-1.68 (IH, m), 1.21 (3H, t, J = 7.1). HRMS (FAB) 539.2283 (MNa + , calcd. 539.2270). Anal. (C 29 H 32 N 4 O 5 - 0.7 H 2 O + 0.1 TFA),C, H, N. EXAMPLE 11 6-Carbamoyl-4S-(2S-{[5-(2-methoxy-phenyl)-lH-pyrrole-2-carbonyl]-amino}-3- phenyl-propionylamino)-hex-2(trans)-enoic acid ethyl ester. (Compound 11) 5-(2-Methoxy-phenyl)-lH-pyrrole-2-carboxylic acid chloride was prepared according to the procedure described in Method 4 of Example 2, starting with 2- methoxyphenyl boronic acid. This material was coupled to Phe-Gln resin, and converted to the title compound according to the procedure described in Method 1 of Example 2. Η NMR (CDC1 3 ) δ 10.73 (IH, s), 8.27 (IH, d, J = 8.3), 7.69 (IH, d, J = 7.6), 7.33-7.19 (5H, m), 7.10 (IH, d, J = 8.3), 7.01 (IH, t, J = 7.7), 6.95 (IH, br s), 6.72-6.62 (2H, m), 5.61 (IH, d, J = 15.8), 4.72 (IH, t, J = 7.2), 4.57-4.46 (IH, m), 4.20 (2H, q, J = 7.1), 3.99 (3H, s), 3.22-3.06 (2H, m), 2.32 (2H, t, J = 7.4), 2.03-1.88 (IH, m), 1.82-1.70 (IH, m), 1.32 (3H, t, J = 7.1). HRMS (MALDI) 569.2398 (MNa + , calcd. 569.2376). Anal. (C 30 H 34 N 4 O 6 • 0.9 H 2 O • 0.4 TFA) C, H, N. EXAMPLE 12 6-Carbamoyl-4S-(3 -phenyl-2S- { [5 -(3 ,3 ,3 -trifluoro-propyl)- 1 H-pyrrole-2-carbonyl]- amino}-propionylamino)-hex-2(trans)-enoic acid ethyl ester. (Compound 22) 5-(3,3,3-Trifluoro-propyl)-lH-pyrrole-2-carboxylic acid chloride Method 5 General Experimental: 4,4,4-Trifluorobutyric acid (70.0 mmol, 10.0 g) in CH 2 C1 2 (190 ml) was treated with oxalyl chloride (140 mmol, 12.3 ml) and DMF (1 drop), then heated to reflux for 1 h. Solvent and excess oxalyl chloride were removed from the volatile product by simple distillation ofthe reaction mixture at atmospheric pressure to provide crade 4,4,4-trifluorobutyric acid chloride (6.4 g). J H NMR (CDCI 3 ) δ 3.20 (2H, t, J = 7.2), 2.65-2.45 (2H, m). 4,4,4-Trifluorobutyric acid chloride (6.4 g from above) in CH 2 C1 2 (80 ml) was treated with O,N-dimethylhydroxylamine hydrochloride (60.0 mmol, 5.85 g). The mixture was cooled to 0 °C, then treated with pyridine (160.0 mmol, 12.9 ml), then allowed to warm to room temperature overnight. The mixture was diluted with CH 2 C1 2 (200 ml), then washed with brine(2x50 ml). Solvent was removed from the volatile product by simple distillation at atmospheric pressure to provide 20 g of 4,4,4-trifluoro- N-methoxy-N-methyl butyramide, which may be used without further purification. *H NMR (CDCI 3 ) δ 3.70 (3H, s), 3.19 (3H, s), 2.78-2.65 (2H, m), 2.57-2.40 (2H, m). Mg (92.0 mmol, 2.2 g) in THF (80 ml), under an argon atmosphere, was treated with 2-(2-bromoethyl)-[l,3]dioxolane (80 mmol, 9.4 ml), while keeping the internal temperature below 35 °C with the aid of an ice bath. After the addition was complete, the mixture was stirred for 2 h at room temperature, then cooled to -78 °C. Crade 4,4,4-trifluoro-N-methoxy-N-methyl butyramide (20 g, prepared above) in THF (40 ml) was cooled to -78 °C, then the freshly prepared Grignard reagent was transferred via cannula into the amide solution at -78 °C. The resulting mixture was allowed to warm to room temperature, held at room temperature overnight, then poured into saturated aqueous ammonium chloride (200 ml). The mixture was extracted with ethyl acetate (3x75 ml). The combined organics were washed with brine (2x75 ml) and concentrated under reduced pressure to provide crade l-[l,3]dioxolan-2-yl-6,6,6-trifluoro-hexan-3- one (18 g) Η NMR (CDC1 3 ) δ 4.91 (IH, t, J = 4.1), 3.97-3.82 (4H, m), 2.70 (2H, t, J = 7.3), 2.57 (2H, t, J = 7.2), 2.49-2.34 (2H, m), 2.01 (2H, dt, J = 7.3, 4.1). Crude l-[l,3]dioxolan-2-yl-6,6,6-trifluoro-hexan-3-one (18 g, prepared above) in 1 : 1 2N HCI-dioxane (80 ml) was heated to reflux for 20 minutes, then neutralized with aqueous sodium bicarbonate (100 ml), then extracted with ethyl acetate (3x75 ml). The combined organics were washed with brine (2x50 ml), then concentrated under reduced pressure to provide crade 7,7,7-trifluoro-4-oxo-heptanal (10 g), which maybe used without further purification. Η NMR (CDC1 3 ) δ 9.80 (IH, s), 2.85-2.70 (6H, m), 2.47-2.35 (2H, m). Crude 7,7,7-trifluoro-4-oxo-heptanal (10 g, prepared above) in ethanol (100 ml) was treated with ammonium chloride (400 mmol, 21 g), then heated to reflux for 1 h. The resulting solution was diluted with ethyl acetate (300 ml) and washed with brine (2x50 ml). The organics were concentrated under reduced pressure. Purification ofthe residue by silica gel chromatography provided 1.3 g (21% overall from 4,4,4- trifluorobutyric acid) of 2-(3,3,3-trifluoro-ρropyl)-lH-ρyrrole. Η NMR (CDC1 3 ) δ 7.98 (IH, br s), 6.71 (IH, dd, J = 4.1, 2.6), 6.15 (IH, dd, J = 5.9, 2.8), 5.99-5.94 (IH, m), 2.92-2.85 (2H, m), 2.52-2.35 (2H, m). 2-(3,3,3-Trifluoro-propyl)-lH-pyrrole (8.15 mmol, 1.33 g) was added to a solution of trichloroacetyl chloride (8.15 mmol, 0.91 ml) in diethyl ether (10 ml). The resulting solution was held at room temperature for lh, then concentrated under reduced pressure. The resulting solid was dissolved in 1 : 1 dioxane- water (20 ml), treated with lithium hydroxide (24.5 mmol, 0.59 g), and heated to reflux for 30 minutes. After cooling to room temperature, the solution was acidified with saturated aqueous citric acid (20 ml), then extracted with ethyl acetate (2x50 ml). The combined organics were concentrated under reduced pressure. Purification ofthe resulting solid by silica gel chromatography provided 1.15 g (68%) of 5-(3,3,3-trifluoropropyl)-lH- pyrrole-2-carboxylic acid. Η NMR (CDC1 3 ) δ 9.33 (IH, br s), 6.99 (IH, dd, J = 3.7, 2.5), 6.07 (IH, t, J = 3.3), 2.96-2.89 (2H, m), 2.55-2.39 (2H, m). 5-(3,3,3-trifluoropropyl)-lH-pyrrole-2-carboxylic acid (5.55 mmol, 1.15 g) in CH 2 C1 2 (10 ml) was treated with oxalyl chloride (16.7 mmol, 1.5 ml), then DMF (1 drop). The solution was heated to reflux for 1 h, then concentrated under reduced pressure to provide 5-(3,3,3-trifluoropropyl)-lH-pyrrole-2-carboxylic acid chloride (1.04 g). Η NMR (CDCI 3 ) δ 10.25 (IH, br s), 7.12 (IH, dd, J = 4.0, 2.6), 6.12 (IH, dd, J = 3.8, 2.7), 3.05-2.88 (2H, m), 2.59-2.41 (2H, m). The 5-(3,3,3-trifluoro-propyl)-lH-pyrrole-2-carboxylic acid chloride was coupled to Phe-Gln resin, and converted to the title compound according to the procedure described in Method 1 of Example 2. Η NMR (CDC1 3 ) δ 10.30 (IH, br s), 7.41 (IH, d, J = 8.5), 7.29-7.13 (4H, m), 6.61 (IH, dd, J = 15.7, 5.3), 6.63 (IH, m), 5.93 (IH, br s), 5.53 (IH, dd, J = 15.7, 1.3), 4.65 (IH, t, J = 7.1), 4.53-4.42 (IH, m), 4.15 (2H, q, J = 7.1), 3.05-3.00 (2H, m), 2.88-2.79 (2H, m), 2.45-2.30 (2H, m), 2.20-2.10 (2H, m), 1.86-1.83 (IH, m), 1.75-1.66 (IH, m), 1.27 (3H, t, J = 7.1). HRMS (MALDI) 559.2131 (MNa + , calcd. 559.2144). EXAMPLE 13 6-Carbamoyl-4S-{3-phenyl-2S-[(5-pyridin-3-yl-lH-pyrrole-2-carbonyl)-amino]- propionylamino}-hex-2(trans)-enoic acid ethyl ester. (Compound 8) 5-Pyridin-3-yl-lH-pyrrole-2-carboxylic acid chloride was prepared according to the procedure described in Method 5 of Example 12, starting with 3-pyridine carboxylic acid. This material was coupled to Phe-Gln resin, and converted to the title compound according to the procedure described in Method 1 of Example 2. ! H NMR (CD 3 OD) δ 8.88 (IH, s), 8.41 (IH, d, J = 3.4), 8.11 (IH, d, J = 7.9), 7.46 (IH, dd, J = 8.0, 4.5), 7.29-7.19 (5H, m), 6.90 (IH, d, J = 3.9), 6.68 (IH, d, J = 3.9), 6.66 (IH, dd, J = 15.6, 5.6), 5.59 (IH, d, J = 15.6), 4.71 (IH, t, J = 7.7), 4.51-4.48 (1H, m), 4.19 (2H, q, J = 7.1), 3.11 (2H, t, J = 8.5), 2.25-2.10 (2H, m), 1.96-1.82 (IH, m), 1.75-1.60 (IH, m), 1.28 (3H, t, J = 7.1). HRMS (MALDI) 540.2217 (MNa + , calcd. 540.2223). EXAMPLE 14 4S-{2S-[(5 -Benzo { 1 ,3] dioxol-4-yl- 1 H-pyrrole-2-carbonyl)-amino-3 -phenyl- propionylamino}-6-carbamoyl-hex-2(trans)-enoic acid ethyl ester. (Compound 12) 5-Benzo[l,3]dioxol-4-yl-lH-pyrrole-2-carboxylic acid chloride was prepared according to the procedure described in Method 5 of Example 12, starting with benzo[l,3]dioxole-4-carboxylic acid. This material was coupled to Phe-Gln resin, and converted to the title compound according to the procedure described in Method 1 of Example 2. Η NMR (CD 3 OD) δ 7.32-7.24 (5H, m), 7.18 (IH, dd, J = 7.1, 1.1), 6.95 (IH, d, J = 3.9), 6.89 (IH, t, J = 5.1), 6.75 (IH, dd, J = 7.7, 1.1), 6.70-6.63 (2H, m), 6.08 (2H, s), 5.58 (IH, d, J = 15.3), 4.70 (IH, t, J = 7.7), 4.55-4.42 (IH, m), 4.18 (2H, q, J = 7.2), 3.10 (2H, t, J = 8.0), 2.31 (2H, t, J = 8.5), 1.96-1.82 (IH, m), 1.75-1.60 (IH, m), 1.27 (3H, t, J = 7.1). HRMS (FAB) 583.2148 (MNa + , calcd. 583.2169). EXAMPLE 15 6-Carbamoyl-4S-(3-phenyl-2S-{[5-(3,3,3-trifluoro-l-methyl-propyl)-lH-pyrrole-2- carbonyl] -amino }-propionylamino)-hex-2(trans)-enoic acid ethyl ester. (Compound 13) 5-(3,3,3-trifluoro-l-methyl-propyl)-lH-pyrrole-2-carboxylic acid chloride was prepared according to the procedure described in Method 5 of Example 12, starting with 4,4,4-trifluoro-2 -methyl butyric acid. This material was coupled to Phe-Gln resin, and converted to the title compound according to the procedure described in Method 1 of Example 2. Η NMR (CDC1 3 ) δ 10.00 (IH, br s), 7.32-7.16 (5H, m), 6.99 (IH, d, J = 6.9), 6.77 (IH, br s), 6.67 (IH, dd, J = 15.7, 5.4), 6.62-6.58 (IH, m), 6.20-6.01 (2H, m), 5.97 (IH, t, J = 3.0), 5.66 (IH, d, J = 15.9), 4.86-4.75 (IH, m), 4.60-4.48 (IH, m), 4.17 (2H, q, J = 7.1), 3.23-3.04 (3H, m), 2.52-2.38 (lH,m), 2.22-2.12 (3H,m), 1.83-1.70 (IH, m), 1.23 (3H, d, J = 7.0), 1.30 (3H, t, J = 7.2). HRMS (MALDI) 573.2295 (MNa + , calcd. 573.2301). Anal. (C 27 H 33 N 4 O 5 F 3 • 0.1 TFA) C, H, N. EXAMPLE 16 4S-(2S-{[5-(2-Bromo-phenyl)-lH-pyrrole-2-carbonyl]-amino}-3-phenyl- propionylamino)-6-carbamoyl-hex-2(trans)-enoic acid ethyl ester. (Compound 14) 5-(2-bromo-phenyl)-lH-pyrrole-2-carboxylic acid chloride was prepared according to the procedure described in Method 5 of Example 12, starting with 2- bromobenzoic acid. This material was coupled to Phe-Gln resin, and converted to the title compound according to the procedure described in Method 1 of Example 2. *H NMR (CDCI 3 ) δ 10.30 (IH, br s), 7.56 (IH, d, J = 7.9), 7.41 (IH, dd, J = 7.7, 1.5), 7.31-7.13 (7H, m), 7.08 (IH, dt, J = 7.8, 1.2), 7.01 (IH, d, J = 8.6), 6.80-6.74 (IH, m), 6.64 (IH, dd, J = 15.7, 5.3), 6.54-6.49 (IH, m), 6.26 (IH, br s), 6.14 (IH, br s), 5.63 (IH, dd, J = 15.7, 1.2), 4.83-4.72 (IH, m), 4.58-4.46 (IH, m), 4.37 (2H, q, J = 7.1), 3.20-3.02 (2H, m), 2.25-2.10 (2H, m), 1.96-1.82 (IH, m), 1.75-1.60 (IH, m), 1.29 (3H, t, J = 7.1). HRMS (MALDI) 617.1365 (MNa + , calcd. 617.1376). Anal. (C 29 H 31 N 4 O 5 Br • 0.2 H 2 O • 0.3 TFA) C, H, N. EXAMPLE 17 6-Carbamoyl-4S- {3-phenyl-2S-[(5-pyridin-4-yl-lH-pyrrole-2-carbonyl)-amino]- propionylamino}-hex-2(trans)-enoic acid ethyl ester. (Compound 15) 5-Pyridin-4-yl-lH-pyrrole-2-carboxylic acid chloride was prepared according to the procedure described in Method 5 of Example 12, starting with 4-pyridine carboxylic acid. This material was coupled to Phe-Gln resin, and converted to the title compound according to the procedure described in Method 1 of Example 2. ! H NMR (CD 3 OD) δ 8.50 (2H, d, J = 6.7), 7.70 (2H, d, J = 6.4), 7.30-7.19 (5H, m), 6.97 (IH, d, J = 3.9), 6.84 (IH, d, J = 4.0), 6.66 (IH, dd, J = 15.8, 5.6), 5.59 (IH, d, J = 15.7), 4.72 (IH, t, J = 15.4), 4.60-4.40 (IH, m), 4.18 (2H, q, J = 7.1), 3.17 (2H, t, J = 7.9), 2.25-2.10 (2H, m), 1.96-1.82 (IH, m), 1.75-1.60 (IH, m), 1.28 (3H, t, J = 7.1). HRMS (MALDI) 540.2217 (MNa + , calcd. 540.2223). EXAMPLE 18 6-Carbamoyl-4S-(2S-{[5-(2-trifluoromethyl-phenyl)-lH-pyπ , ole-2-carbonyl]-amino}- pent-4-ynoylamino)-hex-2(trans)-enoic acid ethyl ester. (Compound 16) Gln-resin was coupled with Fmoc-propargyl glycine, deprotected, then coupled to 5-(2-trifluoromethyl-phenyl)-lH-pyrrole-2-carboxylic acid chloride (prepared according to the procedure described in Method 6 of Example 4), following Method 1 of Example 2. Η NMR (CDC1 3 ) δ 10.13 (IH, s), 7.73 (IH, d, J = 7.8), 7.60-7.40 (4H, m), 7.15 (IH, d, J = 7.6), 6.90-6.75 (2H, m), 6.38 (IH, s), 6.15 (2H, br s), 6.02 (IH, d, J = 16.3), 4.78-4.68 (IH, m), 4.68-4.55 (IH, m), 4.15 (2H, q, J = 7.1), 2.80-2.20 (4H, m), 2.12 (IH, s), 2.08-1.90 (IH, m), 1.90-1.75 (IH, m), 1.25 (3H, t, J = 7.1). HRMS (MALDI) 555.1828 (MNa + , calcd. 555.1831). Anal. (C 26 H 27 F 3 N 4 O 5 • 0.8 H 2 O). EXAMPLE 19 6-Carbamoyl-4S-(4-methyl-2S-{[5-(2-trifluoromethyl-phenyl)-lH-pyrrole-2-carbonyl]- amino}-pentanoylamino)-hex-2(trans)-enoic acid ethyl ester. (Compound 17) Gln-resin was coupled with Fmoc-leucine, deprotected, then coupled to 5-(2- trifluoromethyl-phenyl)-lH-pyrrole-2-carboxylic acid chloride (prepared according to the procedure described in Method 6 of Example 4), following Method 1 of Example 2. Η NMR (CDC1 3 ) δ 10.06 (IH, s), 7.70 (IH, d, J = 7.6), 7.60-7.38 (4H, m), 7.13 (IH, d, J = 7.8) 6.88-6.75 (2H, m), 6.36 (2H, br s), 6.19 (IH, br s), 5.91 (IH, d, J = 15.5), 4.72- 4.60 (IH, ), 4.60-4.45 (IH, m), 4.17 (2H, q, J = 7.1), 2.28-2.15 (2H, m), 2.00-1.85 (IH, m), 1.80-1.60 (4H, m), 1.27 (3H, t, J = 7.1), 0.92 (3H, d, J = 5.5), 0.88 (3H, d, J = 5.5). HRMS (MALDI) 573.2292 (MNa + , calcd. 573.2301). Anal. (C 27 H 33 N 4 F 3 O 5 • 0.2 H 2 0 . 0.2 TFA) C, H, N. EXAMPLE 20 6-Carbamoyl-4S-(2S-{[5-(2-trifluoromethyl-phenyl)-lH-pyrrole-2-carbonyl]-amino}- pentanoylamino)-hex-2(trans)-enoic acid ethyl ester. (Compound 18) Gln-resin was coupled with Fmoc-norvaline, deprotected, then coupled to 5-(2- trifluoromethyl-phenyl)-lH-pyrrole-2-carboxylic acid chloride (prepared according to the procedure described in Method 6 of Example 4), following Method 1 of Example 2. Η NMR (CDC1 3 ) δ 10.21 (IH, s), 7.69 (IH, d, J = 7.7), 7.64 (IH, d, J = 8.0), 7.55-7.33 (4H, m), 6.88-6.75 (2H, m), 6.45-6.20 (3H, m), 5.91 (IH, d, J = 15.7), 4.65-4.50 (2H, m), 4.15 (2H, q, J = 7.1), 2.25-2.15 (2H, m), 2.00-1.60 (4H, m), 1.48-1.28 (2H, m), 1.25 (3H, t, J = 7.1), 0.89 (3H, t, J = 7.2). HRMS (MALDI) 559.2158 (MNa + , calcd. 559.2144). EXAMPLE 21 6-Carbamoyl-4S-(2S- {[5-(2-trifluoromethyl-phenyl)- lH-pyrrole-2-carbonyl]-amino} - hexanoylamino)-hex-2(trans)-enoic acid ethyl ester. (Compound 19) Gln-resin was coupled with Fmoc-norleucine, deprotected, then coupled to 5-(2- trifluoroniethyl-phenyl)-lH-pyrrole-2-carboxylic acid chloride (prepared according to the procedure described in Method 6 of Example 4), following Method 1 of Example 2. Η NMR (CDCI 3 ) δ 10.08 (IH, br s), 7.71 (IH, d, J = 7.7), 7.56-7.38 (4H, m), 7.09 (IH, d, J = 7.9), 6.88-6.76 (2H, m), 6.37 (IH, s), 6.32 (IH, br s), 6.18 (IH, br s), 5.92 (IH, d, J = 15.0), 4.64-4.52 (2H, m), 4.16 (2H, q, J = 7.1), 2.30-2.15 (2H, m), 2.00-1.65 (4H, m), 1.40-1.22 (7H, m), 0.87 (3H, t, J = 6.3). HRMS (MALDI) 573.2307 (MNa + , calcd. 573.2301). EXAMPLE 22 6-Carbamoyl-4S-(2S-{[5-(2-trifluoromethyl-phenyl)-lH-pyrrole-2-carbonyl]-an ino}- acetylamino)-hex-2(trans)-enoic acid ethyl ester. (Compound 20) Gln-resin was coupled with Fmoc-glycine, deprotected, then coupled to 5-(2- trifluoromethyl-phenyl)-lH-pyrrole-2-carboxylic acid chloride (prepared according to the procedure described in Method 6 of Example 4), following Method 1 of Example 2. Η NMR (CD 3 OD) δ 11.18 (IH, s), 7.79 (IH, d, J = 7.8), 7.70-7.50 (3H, m), 6.92-6.88 (IH, m), 6.85 (IH, d, J = 5.5), 6.32 (IH, m), 5.97 (IH, dd, J = 15.7, 1.7), 4.64-4.54 (IH, m), 4.17 (2H, q, J = 7.1), 4.02 (2H, d, J = 2.4), 2.35-2.27 (2H, m), 2.06-1.94 (IH, m), 1.90-1.75 (IH, m), 1.27 (3H, t, J = 7.1). HRMS (MALDI) 495.1874 (MNa + , calcd. 495.1855). EXAMPLE 23 6-Carbamoyl-4S-(2S-{[5-(3-methyl-isoxazol-5-yl)-lH-pyrrole-2-carbonyl]-amino}-3- phenyl-propionylamino)-hex-2(trans)-enoic acid ethyl ester. (Compound 21) 3-Methyl-5-(lH-pyrrol-2-yl)-isoxazole (Sundberg, et al., J. Org. Chem., 1985, 50, 425) was converted to 5-(3-methyl-isoxazol-5-yl)-lH-pyrrole-2-carboxylic acid chloride according to the procedure described in Method 5 of Example 12, then coupled to Phe-Gln resin following Method 1 of Example 2, then cleaved from resin to provide the title compound. Η NMR (CD 3 OD) δ 7.31-7.19 (6H, m), 6.93 (IH, d, J = 3.9), 6.67 (IH, d, J = 4.0), 6.64 (IH, dd, J = 15.3, 5.7), 6.49 (IH, s), 5.57 (IH, dd, J = 15.8, 0.9), 4.69 (IH, t, J = 15.6), 4.55-4.46 (IH, m), 4.18 (2H, q, J = 7.1), 3.12 (2H, t, j = 7.6), 2.31 (2H, q, = 8.0), 2.05-1.94 (IH, m), 1.83-1.74 (IH, m), 1.28 (3H, t, J = 7.1). HRMS 544.2163 (MNa + , calcd. 544.2172). EXAMPLE 24 6-Carbamoyl-4S-(2S-{[5-(2-trifluoromethyl-phenyl)-lH-pyixole-2-carbonyl]-amino}- butyrlamino)-hex-2(trans)-enoic acid ethyl ester. (Compound 23) Gln-resin was coupled with Fmoc-aminobutyric acid, deprotected, then coupled to 5-(2-trifluoromethyl-phenyl)-lH-pyrrole-2-carboxylic acid chloride (prepared according to the procedure described in Method 6 of Example 4), following Method 1 of Example 2. Η NMR (CDC1 3 ) δ 10.06 (IH, br s), 7.72 (IH, d, J = 7.7), 7.63-7.37 (4H, m), 7.02 (IH, d, J = 7.5), 6.88-6.76 (2H, m), 6.37 (IH, s), 6.28 (IH, br s), 6.18 (IH, br s), 5.92 (IH, d, J = 15.8), 4.68-4.45 (2H, m), 4.16 (2H, q, J = 7.1), 2.34-2.22 (2H, m), 2.04-1.65 (4H, m), 1.26 (3H, t, J = 7.1), 0.95 (3H, t, j = 7.1). HRMS (MALDI) 545.2002 (MNa + , calcd. 545.1988). EXAMPLE 25 5-Naphthalen- 1 -yl- lH-pyrrole-2-carboxylic acid- { 1 S-[2-oxo-dihydrofuran-3-ylidine)- 1 - (2-oxo-pyπ , olidin-3S-memyl)-ethyl carbamoyl]-2S-(4-fluoro-phenyl-emyl)}-amide. (Compound 26) Method 2 General Experimental: Boc-protected 3S-[2S-amino-3-(2-oxo- dihydro-furan-3-ylidine)-propyl]-pyrrolidin-2-one, prepared by a method analogous to that described in Tian, et al., U.S. Provisional Patent Application No. 60/150,358, filed August 24, 1999 and also Baldwin et al., J. Org. Chem., 1971, 36, 1441, (3.40 mmol, 1.10 g) in CH 2 C1 2 (10 ml) was treated with HCl (17.0 mmol, 4.3 ml of 4M in dioxane), and held at room temperature for 1 h, then concentrated under reduced pressure. The product was diluted with DMF (10 ml), treated with Boc-4-fluoro-phenylalanine (3.40 mmol, 0.96 g), DIEA (10.2 mmol, 1.8 ml), and HATU (3.40 mmol, 1.29 g), then held at room temperature for lh. The resulting solution was diluted with in ethyl acetate (75 ml), washed with brine (3x20 ml), then concentrated under reduced pressure. The residue was purified by silica gel chromatography to provide 0.84 g (51%) of2-(4-fluorophenyl)-lS-[2-(2-oxodihydrofuran-3-ylidine)-l-(2-oxo-pyrrolidin- 3S-ylmethyl)-ethyl carbamoyl]-ethyl-carbamic acid t-butyl ester. H NMR (CDC1 3 ) δ 7.82 (IH, br s), 7.15-7.07 (2H, m), 6.96 (2H, t, J = 8.7), 6.32 (IH, d, J = 8.2), 6.00 (IH, s), 5.22 (IH, d, J = 7.8), 4.55-4.32 (4H, m), 3.40-3.28 (2H, m), 3.28-3.10 (IH, m), 3.05- 2.95 (2H, m), 2.95-2.83 (IH, m), 2.50-2.20 (2H, m), 2.10-1.90 (IH, m), 1.90-1.70 (2H, m), 1.58-1.46 (IH, m), 1.39 (9H, s). 2-(4-Fluorophenyl)-lS-[2-(2-oxodihydrofuran-3-ylidine)-l-(2-oxo-pyrrolidin- 3S-ylmethyl)-ethyl carbamoyl]-ethyl-carbamic acid t-butyl ester (0.96 mmol, 0.47 g) in CH 2 C1 2 (5 ml) was treated with HCl (4.8 mmol, 1.2 ml of 4M in dioxane), and held 1 h, then concentrated under reduced pressure. The product was diluted with CH 2 C1 2 (5 ml) and collidine (2.89 mmol, 0.38 ml), and treated with 5-naphthalene-l-yl-lH-pyrrole-2- carboxylic acid chloride (prepared according to the procedure described in Method 4 of Example 2, starting with 1-naphthalene boronic acid, 0.96 mmol, 0.25 g), then held at room temperature for 1 h. The resulting solution was diluted with ethyl acetate (75 ml), washed with saturated aqueous sodium bicarbonate (2x20 ml) and brine (2x20 ml), then concentrated under reduced pressure. Purification ofthe residue by silica gel chromatography gave 0.17 g (29%) of product. Η NMR (CDC1 3 ) δ 10.05 (IH, s), 8.27-8.13 (2H, m)7.92-7.80 (2H, m), 7.57-7.45 (4H, m), 7.20-7.11 (2H, m), 7.05-6.95 (3H, m), 6.73 (IH, d, J = 9.6), 6.51 (IH, dd, J = 3.7, 2.6), 6.32 (IH, DT, J = 8.5, 2.9), 5.36 (IH, br s), 5.15-5.05 (IH, m), 4.46-4.32 (3H, m), 3.42-3.18 (4H, m), 3.02-2.82 (2H, m), 2.36-2.25 (IH, m), 1.90-1.65 (3H, m), 1.60-1.48 (IH, m). HRMS (FAB) 741.1466 (MCs + , calcd. 741.1489). EXAMPLE 26 5-(2-Oxo-pyrrolidin-3S-yl)-4S-{3-ρhenyl-2S-[(lH-ρyrrole-2-carbonyl)-amino]- propionylamino}-pent-2(trans)-enoic acid ethyl ester. (Compound 24) 4S-Ammo-5-(2-oxo-pyrrolidin-3S-yl)-pent-2(trans)-enoic acid ethyl ester was coupled to Boc-phenylalanine, then deprotected and coupled to pyrrole-2-carboxylic acid chloride, following Method 2 of Example 25. Η NMR (CD 3 OD) δ 7.23-7.08 (5H, m), 6.82 (IH, dd, J = 2.5, 1.4), 6.71 (IH, dd, J = 3.8, 1.4), 6.58 (IH, dd, J = 10.2, 5.5), 6.13 (IH, dd, J = 3.8, 2.5), 5.57 (IH, dd, J = 15.8, 1.6), 4.74 (IH, t, J = 6.8), 4.47-4.36 (IH, m), 4.10 (2H, q, J = 7.1), 3.11-2.94 (2H, m), 2.27-2.13 (2H, ), 1.84-1.57 (IH, m), 1.49-1.38 (IH, m), 1.21 (3H, t, J = 7.1). HRMS (FAB) 467.2299 (MH + , calcd. 467.2294). EXAMPLE 27 4S-{2S-[(5-Naphthalen-l-yl-lH-pyrrole-2-carbonyl)-amino]-3-phenyl- propionylamino}-5-(2-oxo-pyrrolidin-3S-yl)-pent-2-enoic acid ethyl ester. (Compound 25) 4S-Amino-5-(2-oxo-pyrrolidin-3S-yl)-pent-2(trans)-enoic acid ethyl ester was coupled to Boc-phenylalanine, then deprotected and coupled to 5-naphthalen-l-yl- pyrrole-2-carboxylic acid chloride (prepared according to the procedure described in Method 4 of Example 2, starting with 1 -naphthyl boronic acid) following Method 2 of Example 25. Η NMR (CDC1 3 ) δ 10.28 (IH, s), 8.21 (IH, d, J = 9.0), 7.83-7.80 (3H, m), 7.57-7.44 (4H, m), 7.34-7.18 (5H, m), 7.02-6.96 (IH, m), 6.74 (IH, d, J = 9.1), 6.67 (IH, dd, J = 10.2, 5.4), 6.52-6.46 (IH, m), 5.75 (IH, d, J = 15.6), 5.18 (IH, br s), 5.13- 5.03 (IH, m), 4.47-4.36 (IH, m), 4.17 (2H, q, J = 7.1), 3.41-3.31 (IH, m), 3.17-3.07 (2H, m), 3.06-2.97 (IH, m), 2.30-2.18 (IH, m), 2.05-1.92 (IH, m), 1.80-1.58 (2H, m), 1.55-1.45 (IH, m), 1.27 (3H 5 1, J = 7.1). HRMS (FAB) 593.2750 (MH 1" , calcd. 593.2764). EXAMPLE 28 5-Phenyl- lH-pyrrole-2-carboxylic acid- {2S-(4-fluorophenyl)- 1 S-[ 1 -(2-oxo- dmydrofuran-3-ylidinemethyl)-l-(2-oxo-pyrrolidin-3S-methyl)-ethyl carbamoyl]-2S- phenyl-ethyl} -amide. (Compound 27) 2-(4-Fluorophenyl)-lS-[2-(2-oxod ydrofuran-3-ylidine)-l-(2-oxo-pyrrolidin- 3S-ylmethyl)-ethyl carbamoyl]-ethyl-carbamic acid t-butyl ester (prepared as described in Method 2 of Example 25) was deprotected, then coupled to 5-phenyl-lH-pyrrole-2- carboxylic acid chloride (prepared according to the procedure described in Method 5 of Example 12, starting with benzoic acid), following Method 2 of Example 25. *H NMR (CDC1 3 ) δ 10.48 (IH, s), 7.56 (2H, d, J = 7.3), 7.36 (2H, t, J = 7.7), 7.26-7.19 (IH, m), 7.14-7.06 (2H, m), 6.93 (2H, t, J = 8.7), 6.85-6.81 (IH, m), 6.51-6.47 (IH, m), 6.28 (IH, dt, J = 8.8, 3.9), 4.83 (IH, t, J = 5.2), 4.50-4.39 (IH, m), 4.34 (2H, t, J = 7.6), 3.30- 3.27 (2H, m), 3.18-2.90 (3H, m), 2.91-2.76 (IH, m), 2.36-2.13 (2H, m), 1.98-1.85 (IH, m), 1.80-1.66 (IH, m), 1.53-1.43 (IH, m). HRMS (FAB) 581.2161 (MNa + , calcd. 581.2176). EXAMPLE 29 5-(2-Oxo-ρyrrolidm-3S-yl)-4S-(3-ρhenyl-2S-{[5-(2-trifluoromethyl-phenyl)-lH- pyrrole-2-carbonyl]-amino} -propionylamino)-pent-2(trans)-enoic acid ethyl ester. (Compound 28) 4S-Amino-5-(2-oxo-pyrrolidin-3S-yl)-pent-2(trans)-enoic acid ethyl ester was coupled to Boc-phenylalanine, then deprotected and coupled to 5-(2-trifluoromethyl- phenyl)-lH-pyrrole-2-carboxylic acid chloride (prepared according to the procedure described in Method 6 of Example 4, starting with 2-trifluoromethyl benzaldehyde) following Method 2 of Example 25. Η NMR (CDCI 3 ) δ 10.00 (IH, s), 7.75-7.65 (2H, m), 7.57-7.35 (3H, m), 7.30-7.13 (4H, m), 6.98 (IH, d, J = 8.8), 6.84 (IH, br s), 6.65 (IH, dd, J = 10.2, 5.4), 6.38 (IH, br s), 6.15 (IH, br s), 5.72 (IH, d, J = 14.7), 5.10-4.98 (IH, m), 4.52-4.40 (IH, m), 4.17 (2H, q, J = 7.1), 3.28-3.15 (3H, m), 3.00 (IH, dd, J = 13.4, 7.0), 2.32-2.20 (IH, m), 2.18-2.05 (IH, m), 1.88-1.60 (2H, m), 1.58-1.48 (IH, m), 1.27 (3H, t, J = 7.1). HRMS (MALDI) 611.2475 (MH*, calcd. 611.2481). Anal. (C 32 H 33 N 4 O 5 F 3 • 1.0 H 2 O) C, H, N. EXAMPLE 30 5-(2-Oxo-pyrrolidin-3S-yl)-4S-(2S-{[5-(2-trifluoromethyl-phenyl)-lH-ρyrrole-2- carbonyl]-amino}-pent-4-ynoylamino)-pent-2(trans)-enoic acid ethyl ester. (Compound 29) 4S-Amino-5-(2-oxo-pyrrolidin-3S-yl)-pent-2(trans)-enoic acid ethyl ester was coupled to Boc-propargyl glycine, then deprotected and coupled to 5-(2- trifluoromethyl-phenyl)-lH-pyrrole-2-carboxylic acid chloride (prepared according to the procedure described in Method 6 of Example 4, starting with 2-trifluoromethyl benzaldehyde) following Method 2 of Example 25. Η NMR (CDC1 3 ) δ 10.13 (IH, s), 8.10 (IH, d, J = 7.4), 7.73 (IH, d, J = 7.8), 7.59-7.40 (3H, m), 7.19 (IH, d, J = 8.4), 6.88 (IH, dd, J = 3.8, 2.5), 6.83 (IH, dd, J = 15.7, 5.0), 6.43-6.35 (IH, m), 6.03 (IH, dd, J = 15.7, 1.6), 4.92-4.83 (IH, m), 4.65-4.54 (IH, m), 4.15 (2H, q, J = 7.1), 3.32- 3.23 (2H, m), 2.87-2.61 (2H, m), 2.50-2.22 (2H, m), 2.06 (IH, t, J = 2.5), 2.00-1.92 (IH, m), 1.86-1.58 (2H, m), 1.25 (3H, t, J = 7.1). HRMS (MALDI) 581.1992 (MNa + , calcd. 581.1988). Anal. (C 28 H 29 N 4 O 5 F 3 . 0.5 H 2 O) C, H, N. EXAMPLE 31 6-Carbamoyl-4S-(2S{methyl-[5-(2-trifluoromethyl-phenyl)-lH-pyrrole-2-carbonyl]- amino}-3-phenyl-propionylamino)-hex-2(trans)-enoic acid ethyl ester. (Compound 41) Gln-resin was coupled with Fmoc-N-methyl-phenylalanine, according to the procedure described in Method 1 of Example 2, then deprotected and coupled with 5- (2-trifluoromethyl-phenyl)-lH-pyrrole-2-carboxylic acid (prepared according to the procedure described in Method 6 of Example 4), according to the procedure described in Method 1 of Example 2. l U NMR (CD 3 OD) δ 7.90-7.50 (4H, m), 7.35-7.15 (5H, m), 6.88 (IH, dd, J = 15.8, 5.4), 6.60-6.58 (IH, m), 6.38-6.32 (IH, m), 5.98 (IH, dd, J = 15.8, 1.6), 5.32-5.20 (IH, m), 4.65-4.50 (IH, m), 4.25-4.10 (2H, m), 4.18 (2H, q, J = 7.1), 3.50-3.10 (5H, m), 2.33-2.20 (2H, m), 2.03-1.72 (2H, m), 1.23 (3H, t, J = 7.1). HRMS (MALDI) 621.2301 (MNa + , calcd. 621.2301). EXAMPLE 32 4S-[2(R,S)-Berizyl-4-oxo-4-(lH-pyrrol-2-yl)-butyrylamino-5-(2-oxo-pyrrolidin-3S-yl)- pent-2(trans)-enoic acid ethyl ester. 2(R,S)-Benzyl-4-oxo-4-(lH-pyrrol-2-yl)-butryric acid Method 7 General Experimental: Pyrrole-2-carboxylic acid (27.0 mmol, 3.00 g) in CH 2 C1 2 (100 ml) was treated with oxalyl chloride (54.0 mmol, 4.70 ml) and DMF (1 drop), then heated to reflux for 1 h, then concentrated under reduced pressure. The residue was diluted with CH 2 C1 2 (100 ml) and pyridine (6.50 ml), and treated with O,N- dimethyl-hydroxylamine hydrochloride (27.0 mmol, 2.65 g), then held at room temperature overnight. The resulting solution was diluted with ethyl acetate (250 ml), washed with 10% aqueous citric acid (2x30 ml), saturated aqueous sodium bicarbonate (2x30 ml), then brine (2x30 ml). The organics were concentrated under reduced pressure. Purification ofthe residue by silica gel chromatography provided 3.42 g (82%) of lH-pyrrole-2-carboxylic acid methoxy-methyl amide. H NMR (CDC1 3 ) δ 6.90-6.80 (IH, m), 6.79-6.60 (IH, m), 6.18 (IH, dd, J = 3.7, 1.3), 3.81 (3H, s), 3.01 (3H, s). lH-pyrrole-2-carboxylic acid methoxy-methyl amide (22.2 mmol, 3.42 g) in THF (100 ml) was cooled to -78 °C, and treated with methyl lithium-lithium bromide complex (44.4 mmol, 29.6 ml of 1.5 M in Et,O). The solution was held at -78 °C for 20 minutes, allowed to warm to 0 °C, and held 30 minutes, then poured into saturated aqueous ammonium chloride (300 ml). The mixture was extracted with ethyl acetate (3x150 ml). The combined organic extracts were washed with brine (3x50 ml) and concentrated under reduced pressure. The residue was purified by silica gel chromatography to provide 2.28 g (94%) of l-(lH-pyrrol-2-yl)-ethanone. H NMR (CDC1 3 ) δ 7.03 (IH, dt, J = 2.7, 1.3), 6.91 (IH, ddd, J = 3.8, 2.4, 1.3), 6.30-6.26 (IH, m), 2.44 (3H, s). l-(lH-pyrrol-2-yl)-ethanone (2.67 mmol, 0.29 g) in CH 2 C1 2 (10 ml) and Et 3 N (13.3 mmol, 1.90 ml) was cooled to 0 °C and treated with trimethylsilyl trifluoromethanesulfonate (5.34 mmol, 1.00 ml). The solution was held at 0 °C for 30 minutes, then diluted with ethyl acetate (75 ml) and washed with saturated aqueous sodium bicarbonate (2x20 ml) then brine (30 ml). The solution was concentrated under reduced pressure to provide crude 2-[l-(trimethyl-silanyloxy)-vinyl]-lH-pyrrole. *H NMR (CDC1 3 ) δ 6.77 (IH, dd, J = 2.7, 1.6), 6.34 (IH, dd, J = 3.2, 1.6), 6.15 (IH, t, J = 2.8), 4.56 (IH, d, J = 1.0), 4.31 (IH, d, J = 1.0), 0.45 (9H, s), 0.25 (9H, s). Crude 2-[l-(trimethyl-silanyloxy)-vinyl]-lH-pyrrole was diluted with CH 2 C1 2 (10 ml), cooled to 0 °C, and treated with N-bromosuccinimide (1.94 mmol, 0.35 g). The resulting mixture was put in a -20 °C freezer overnight. After warming to room temperature, the mixture was diluted with ethyl acetate (75 ml), washed with saturated aqueous sodium bicarbonate (2x20 ml), brine (2x20 ml), and the organics concentrated under reduced pressure. Purification ofthe residue by silica gel chromatography provided 0.29 g (80%) of 2-bromo-l-(lH-pyrrol-2-yl)-ethanone. l U NMR (CDC1 3 ) δ 7.12 (IH, dt, J = 2.7, 1.3), 7.02 (IH, ddd, J = 3.8, 2.4, 1.3), 6.36-6.31 (IH, m), 4.27 (2H, s). 2-Bromo-l-(lH-pyrrol-2-yl)-ethanone (1.00 mmol, 0.19 g) inDME (3 ml) was treated with Nal (1.00 mmol, 0.15 g), and stirred vigorously for 30 minutes. A solution of diethyl malonate (1.50 mmol, 0.2 ml), NaH (1.00 mmol, 40 mg of 60% in oil), and DME (3 ml) was added to the bromide-Nal mixture, and held at room temperature overnight. Saturated aqueous ammonium chloride (10 ml) was added, then the mixture was extracted with ethyl acetate (2x25 ml). The combined organic extracts washed with brine (25 ml), then concentrated under reduced pressure. Purification ofthe residue by silica gel chromatography provided 0.21 g (79%) of 2-(lH-pyrrole-2- carbonyl)-malonic acid diethyl ester. Η NMR (CDC1 3 ) δ 9.76 (IH, s), 7.04 (IH, dt, J = 2.7, 1.3), 7.00 (IH, ddd, J = 3.8, 2.4, 1.3), 6.30-6.26 (IH, m), 4.21 (4H, m), 4.02 (IH, t, J = 7.3), 3.45 (2H, d, J = 7.3), 1.25 (6H, t, J = 7.1). 2-(lH-Pyrrole-2-carbonyl)-malonic acid diethyl ester (0.79 mmol, 0.21 g) in DME (3 ml) was treated with lithium bis-tiimethylsilylamide (0.79 mmol, 133 mg). The resulting solution was held at room temperature for 30 minutes, then treated with benzyl bromide (0.79 mmol, 0.10 ml). The resulting solution was held at room temperature overnight, then diluted with ethyl acetate (30 ml), and washed with saturated ammonium chloride (10 ml), followed by brine (20 ml). The organics were concentrated under reduced pressure and the residue was purified by silica gel chromatography to provide 0.23 g (84%) of 2-benzyl-2-(lH-pyrrole-2-carbonyl)- malonic acid diethyl ester. Η NMR (CDC1 3 ) δ 10.01 (IH, s), 7.25-7.17 (4H, m), 7.14 (IH, dt, J = 2.7, 1.3), 7.03-6.98 (IH, m), 6.86 (IH, ddd, J = 3.8, 2.4, 1.3), 6.29-6.25 (IH, m), 4.22 (4H, q, J = 7.1), 3.47 (2H, s), 3.39 (2H, s), 1.25 (6H, t, J = 1.7). 2-Benzyl-2-(lH-pyrrole-2-carbonyl)-malonic acid diethyl ester (0.66 mmol, 0.23 g) in 1 : 1 dioxane-water (10 ml) was treated with lithium hydroxide (1.31 mmol, 31 mg), then heated to reflux for 30 minutes. The solution was treated with saturated aqueous citric acid (20 ml), extracted with ethyl acetate (30 ml). The organic extract was washed with brine (15 ml) then concentrated under reduced pressure. The residue was purified by silica gel chromatography to provide 0.11 g (64%) of 2(R,S)-benzyl-4- oxo-4-(lH-pyrrol-2-yl)-butyric acid. Η NMR (CDC1 3 ) δ 7.18-7.04 (5H, m), 6.92 (IH, dd, J = 2.4, 1.4), 6.80 (IH, dd, J = 3.8, 1.3), 6.08 (IH, dd, J = 3.8, 2.5), 3.20-2.85 (3H, m), 2.80-2.67 (2H, m). Method 3 General Experimental: 2(R,S)-Benzyl-4-oxo-4-(lH-pyrrol-2-yl)- butyric acid (0.42 mmol, 0.11 g, prepared according to the procedure described in Example 7), 4S-amino-5-(2-oxo-pyrrolidin-3S-yl)-pent-2(trans)-enoic acid ethyl ester hydrochloride (0.42 mmol, 0.11 g), and DIEA (1.26 mmol, 0.22 ml) in DMF (2 ml) were treated with HATU (0.42 mmol, 0.16 g), then held at room temperature overnight. The resulting solution was diluted with ethyl acetate (30 ml), washed with brine (2x 15 ml). The organics were concentrated under reduced pressure and the residue was purified by silica gel chromatography to provide 0.14 g (75%) of product. The diastereomers were separated by preparative reverse phase HPLC (CH 3 CN-water gradient). 2R-Benzyl diastereomer (Compound 30): Η NMR (CDC1 3 ) δ 11.05 (IH, s), 7.40 (IH, d, J = 8.0), 7.32-7.15 (5H), 7.05 (IH, ddd, J = 3.8, 2.4, 1.3), 7.00-6.96 (2H, m), 6.52 (IH, dd, J = 15.7, 5.0), 6.27-6.23 (IH, m), 5.32 (IH, dd, J = 15.7, 1.6), 4.44- 4.32 (IH, m), 4.14 (2H, q, J = 7.1), 3.53 (IH, dd, J = 14.4, 10.9), 3.34-3.02 (4H, m), 2.85 (IH, dd, J = 13.1, 4.9), 2.57 (IH, dd, J = 14.5, 3.1), 2.20-2.08 (IH, m), 1.98-1.84 (IH, m), 1.72-1.60 (IH, m), 1.60-1.41 (IH, m), 1.40-1.28 (IH, m), 1.28 (3H, t, J = 7.1). HRMS (FAB) 466.2234 (MH + , calcd. 466.2342). EXAMPLE 33 2-(R,S)-(4-Fluorobenzyl)-4-oxo-N-[2-(2-oxo-dihydro-furan-3-ylidine)-lS-(2-oxo- pyrrolidin-3S-ylmethyl)-ethyl]-4-(5-phenyl-lH-pyrrol-2-yl)-butyramide. (Compound 31) 2-(R,S)-(4-Fluorobenzyl)-4-oxo-4-(5-phenyl- lH-pyrrol-2-yl)-butyric acid was prepared according to the procedure described in Example 7, starting with 5-phenyl- lH-pyrrole-2-carboxylic acid (prepared according to the procedure described in Example 4, starting with phenylboronic acid). This material was coupled to 3S-[2S- amino-3 -(2-oxo-dihydro-furan-3 -ylidene)-propyl] pyrrolidin-2-one hydrochloride according to the procedure described in Method 3 of Example 31, to provide the title compound as a 1 : 1 mixture of 2R-2S diastereomers. ! H NMR (CDC1 3 ) δ 10.24 (0.5 H, br s), 9.90 (0.5 H, br s), 7.70-6.85 (11 H, m), 6.61-6.54 (IH, ), 6.37-6.27 (IH, m), 6.27-6.18 (IH, m), 4.50-4.13 (3H, m), 3.42-2.60 (9H, m), 2.25-1.20 (5H, m). HRMS (FAB) 580.2228 (MNa + , calcd. 580.2224). EXAMPLE 34 2-(R,S)-(4-Fluorobenzyl)-4-(5-naρhthalen-l-yl-lH-ρyrrol-2-yl)-4-oxo-N-[2-(2-oxo- dihydro-furan-3-ylidine)-lS-(2-oxo-pyrrolidin-3S-ylmethyl)-ethyl]-butyramide. 2-(R,S)-(4-Fluorobenzyl)-4-oxo-4-(5-naphthalen-l-yl-lH-pyrrol-2-yl)-butyric acid was prepared according to the procedure described in Example 7, starting with 5- naphthalen-l-yl-lH-pyrrole-2-carboxylic acid (prepared according to the procedure described in Example 4, starting with 1-naphthylboronic acid). This material was coupled to 3S-[2S-amino-3-(2-oxo-dihydro-furan-3-ylidene)-propyl] pyrrolidin-2-one hydrochloride according to the procedure described in Method 3 of Example 31, to provide the title compound as a 1:1 mixture of 2R-2S diastereomers. The diastereomers were separated by preparative reverse phase chromatography (acetonitrile-H 2 O gradient). 2R-(4-Fluorobenzyl) diastereomer (Compound 33): Η NMR (CDC1 3 ) δ 10.48 (IH, s), 8.07 (IH, d, J = 8.2), 7.87 (IH, d, J = 7.8), 7.82 (IH, d, J = 8.1), 7.70 (IH, d, J = 5.6), 7.55-7.30 (4H, m), 7.15-7.02 (3H, m), 6.98-6.89 (2H, m), 6.55 (IH, br s), 6.48 (IH, br s), 6.22 (IH, d, J = 8.5), 4.40-4.28 (3H, m), 3.80-1.30 (14H, m). HRMS (FAB) 740.1512 (MCs + , calcd. 740.1537). (4:1 mixture) 2S-(4-Fluorobenzyl) diastereomer (Compound 32): l U NMR (CDC1 3 ) δ 9.81 (IH, br s), 8.04 (IH, d, J = 8.6), 7.85-7.68 (3H, m), 7.52-7.35 (4H, m), 7.20-6.85 (5H, m), 6.50-6.25 (3H, m), 4.35-4.18 (3H, m), 3.28-2.60 (9H, m), 2.20-1.85 (2H, m), 1.70- 1.55 (2H, m), 1.40-1.22 (IH, m). HRMS (FAB) 740.1512 (MCs + , calcd. 740.1537). EXAMPLE 35 2-(R,S)-(4-Fluorobenzyl)-4-oxo-N-[2-(2-oxo-dihydro-furan-3-ylidine)-lS-(2-oxo- pyrrolidin-3S-ylmethyl)-ethyl]-4-(lH-pyrrol-2-yl)-butyramide. (Compound 34) 2-(R,S)-(4-Fluorobenzyl)-4-oxo-4-(lH-pyrrol-2-yl)-butyric acid) was prepared according to the procedure described in Example 7, starting with 2-pyrrolecarboxylic acid. This material was coupled to 3S-[2S-amino-3-(2-oxo-dihydro-furan-3-ylidene)- propyl] pyrrolidin-2-one hydrochloride according to the procedure described in Method 3 of Example 31, to provide the title compound as a 1:1 mixture of 2R-2S diastereomers. Η NMR (CDC1 3 ) δ 10.62 (0.5H, br s), 10.12 (0.5H, br s), 7.83 (0.5H, d, J = 7.7), 7.62 (0.5H, d, J = 7.1), 7.20-6.82 (6H, m), 6.65-6.20 (3H, m), 4.50-4.20 (3H, m), 3.45-2.60 (9H, m), 2.25-1.90 (3H, m), 1.68-1.50 (IH, m), 1.42-1.20 (IH, m). HRMS (FAB) 504.1932 (MNa + , calcd. 504.1911). EXAMPLE 36 5-(2-Oxo-pyrrolidme-3S-yl)-4S-(2R-{2-oxo-2-[5-(2-trifluoromethyl-phenyl)-lH-pyrrol- 2-yl]-ethyl}-pent-4-ynoylamino-pent-2(trans)-enoic acid ethyl ester. (Compound 36) Method 8 General Experimental: 4-Pentynoic acid (60.1 mmol, 5.90 g) in THF (140 ml) was cooled to -78 °C, then treated with Et 3 N (69.1 mmol, 9.60 ml), followed by pivaloyl chloride (61.9 mmol, 7.6 ml). The resulting mixture was allowed to warm to 0 °C, held 30 minutes, then recooled to -78 °C. A solution of 4S-isopropyl-2- oxazolidinone (60.1 mmol, 7.76 g) in THF (140 ml) was cooled to -78 °C and treated with butyllithium (61.9 mmol, 24.8 ml of 2.5M in hexanes), held at -78 °C for 30 minutes, then transferred via cannula at -78 °C into the 4-pentynoic acid -pivaloyl chloride solution. The mixture was held at -78 °C for lh, then warmed to 0 °C and held 30 minutes, then poured into saturated aqueous ammonium chloride (200 ml). The solution was extracted with ethyl acetate (3x150 ml). The combined organic extracts were washed with brine (2x50 ml), then concentrated under reduced pressure to give 12.8 g of 4S-isopropyl-3-pent-4-ynoyl-oxazolidin-2-one, which maybe used without further purification. Η NMR (CDC J δ 4.44-4.37 (IH, m), 4.29-4.15 (2H, m), 3.23- 3.01 (2H, m), 2.50 (2H, dt, J = 7.1, 2.6), 2.39-2.27 (IH, m), 1.93 (IH, t, J = 2.6), 0.87 (3H, d, J = 7.0), 0.82 (3H, d, J = 6.9). 4S-Isopropyl-3-pent-4-ynoyl-oxazolidin-2-one (7.50 mmol, 2.11 g) in THF (25 ml) was cooled to -78 °C and treated with a solution of lithium bis(trimethylsilyl)amide (8.25 mmol, 1.38 g) in THF (5 ml). The resulting solution was allowed to warm to 0 °C, held 15 minutes, then re-cooled to -78 °C , then treated with t-butyl bromoacetate (22.5 mmol, 3.3 ml). The resulting solution was held at -78 °C for 15 minutes, then warmed to 0 °C and held for 2 h. The solution was then poured into saturated aqueous ammonium acetate (30 ml), then extracted with ethyl acetate (2x50 ml). The combined organic extracts were washed with brine (2x15 ml), then concentrated under reduced pressure. The residue was purified by silica gel chromatography to provide 1.23 g (43%) of 3R-(4S-isopropyl-2-oxo-oxazolidine-3- carbonyl)-hex-5-ynoic acid t-butyl ester. l NMR (CDC1 3 ) δ 4.46-4.39 (IH, m), 4.35- 4.16 (3H, m), 2.87 (IH, dd, J = 16.7, 9.8), 2.59-2.27 (4H, m), 2.00 (IH, t, J = 2.6), 1.39 (9H, s), 0.90 (3H, d, J = 3.9), 0.87 (3H, d, J = 4.0). 3R-(4S-Isopropyl-2-oxo-oxazolidine-3-carbonyl)-hex-5-ynoic acid t-butyl ester (10.12 mmol, 3.27 g) in THF (100 ml) and H 2 O (50 ml) was cooled to 0 °C and treated with lithium hydroxide hydrate (20.2 mmol, 0.85 g), followed by H 2 O 2 (41.5 mmol, 4.7 ml of 30% aqueous). The resulting solution was held at 0 °C for 1 h, then allowed to warm to room temperature and held 3 h. The solution was then cooled to 0 °C, and quenched with saturated aqueous sodium bisulfite (30 ml). The solution was acidified with saturated aqueous citric acid (30 ml), and extracted with ethyl acetate (75 ml). The organic extract was washed with brine (30 ml), then concentrated under reduced pressure. The residue was purified by silica gel chromatography to provide 2R-prop-2- ynyl-succinic acid-4-t-butyl ester. This material was treated with diazomethane (30 mmol, generated from N-nitroso-N-methyl urea), then concentrated under reduced pressure to give 1.95 g of 2R-prop-2-ynyl-succinic acid 4-t-butyl ester 1 -methyl ester. This material was treated with 20% TFA -CH 2 C1 2 (30 ml), held 30 min, then concentrated under reduced pressure to give 1.47 g (85%) of 2R-prop-2-ynyl-succinic acid-1-methyl ester. Η NMR (CDC1 3 ) δ 10.12 (IH, br s), 3.08-2.50 (5H, m), 3.73 (3H, s), 2.05 (IH, t, J = 2.7). 2R-Prop-2-ynyl-succinic acid -1 -methyl ester (8.63 mmol, 1.47 g) in CH 2 C1 2 (30 ml) was treated with oxalyl chloride (17.3 mmol, 1.50 ml) and DMF (1 drop), then heated to reflux for 30 minutes, then concentrated under reduced pressure. The residue was diluted with CH 2 C1 2 (30 ml), and pyridine (43.2 mmol, 3.5 ml), then treated with dimethylamine hydrochloride (25.9 mmol, 2.11 g), and held at room temperature overnight. The resulting mixture was diluted with ethyl acetate (150 ml) and washed with brine (3x30 ml). The organics were concentrated under reduced pressure. Purification ofthe residue by silica gel chromatography provided 0.83 g (49%) of 2R- dimethylcarbamoylmethyl-pent-4-ynoic acid methyl ester. 'H NMR (CDC1 3 ) δ 3.69 (3H, s), 3.18-2.52 (11H, m), 2.00 (IH, t, J = 2.7). 2R-Dimethylcarbamoylmethyl-pent-4-ynoic acid methyl ester (4.20 mmol, 0.89 g) was cooled to 0 °C and treated with POCl 3 (4.2 mmol, 0.40 ml). The mixture was allowed to warm to room temperature, and held for lh then diluted with ethylene dichloride (10 ml), and re-cooled to 0 °C. 2-(2-Trifluoromethyl-phenyl)-lH-pyrrole (4.2 mmol, 0.89 g, prepared according to the procedure described in Example 6) in ethylene dichloride (10 ml) was added, and the mixture was allowed to warm to room temperature, then heated to reflux for 2 h. The mixture was then allowed to cool to room temperature, then treated with saturated aqueous sodium acetate (10 ml), and heated to reflux for 15 minutes. The solution was then carefully neutralized with saturated aqueous sodium bicarbonate (20 ml), and extracted with ethyl acetate (75 ml). The organic extract was washed with brine (25 ml), then concentrated under reduced pressure. The residue was purified by silica gel chromatography to provide 1.11 g (72 %) of 2R-(2-oxo-2-[5-(2-trifluoromethyl-ρhenyl)-lH-ρyrrol-2-yl]-ethyl)-pent-4- ynoic acid methyl ester. Η NMR (CDC1 3 ) δ 9.50 (IH, br s), 7.78 (IH, d, J = 7.4), 7.64- 7.46 (3H, m), 7.02 (IH, dd, J = 3.9, 2.5), 6.45 (IH, t, J = 3.0), 3.72 (3H, s), 3.45-3.14 (3H, m), 2.62 (IH, d, J = 2.7), 2.59 (IH, d, J = 2.6), 2.04 (IH, t, J = 2.7). This material was diluted with 1:1 H 2 O-dioxane (40 ml), and treated with lithium hydroxide hydrate (9.18 mmol, 0.38 g), then heated to reflux for 30 minutes. The solution was acidified with saturated aqueous citric acid (20 ml), extracted with ethyl acetate (3x30 ml). The combined organic extracts were washed with brine (3x20 ml), then concentrated under reduced pressure. The residue was purified by silica gel chromatography to provide 0.67 g (60 %) of 2R-(2-oxo-2-[5-(2-trifluoromethyl-phenyl)-lH-pyrrol-2-yl]-ethyl)- pent-4-ynoic acid. 2R-(2-oxo-2-[5 -(2-trifluoromethyl-phenyl)- 1 H-pyrrol-2-yl] -ethyl)-pent-4-ynoic acid was coupled with 4S-amino-5-(2-oxo-pyrrolidin-3S-yl)-pent-2(trans)-enoic acid ethyl ester hydrochloride according to the procedure described in Method 3 of Example 31. Η NMR (CD 3 OD) δ 10.31 (IH, br s), 7.73 (IH, d, J = 7.9), 7.61-7.42 (3H, m), 6.99 (IH, d, J = 4.0), 6.82 (IH, dd, J = 15.7, 4.6), 6.39 (IH, d, J = 3.8), 6.04 (IH, dd, J = 15.7, 1.6), 4.64-4.54 (IH, m), 4.13 (2H, q, J = 7.1), 3.38-2.92 (5H, m), 2.62-2.38 (3H, m), 2.25-2.12 (IH, m), 2.10 (IH, t, J = 2.6), 2.05-1.89 (IH, m), 1.75-1.60 (IH, m), 1.60-1.48 (IH, m), 1.24 (3H, t, J = 7.1). HRMS (MALDI) 558.2221 (MH + , calcd. 558.2216). Anal. (C 29 H 30 N 3 O 5 F 3 • 0.3 H 2 O) C, H, N. EXAMPLE 37 4S-{2R-Benzyl-4-oxo-4-[5-(2-trifluoromethyl-phenyl)-lH-pymol-2-yl]-butyrylamino}- 5-(2-oxo-pyrrolidin-3S-yl)-pent-2(trans)-enoic acid ethyl ester. (Compound 35) 2R-Benzyl-N,N-dimethyl-succinamic acid was prepared according to the procedure described in Example 8, starting with hydrocinnamic acid. This material was reacted with 2-(2-trifluoromethyl-phenyl)-lH-pyrrole (prepared according to the procedure described in Example 6), then demethylated to give 2R-benzyl-4-oxo-4-[5- (2-trifluoromethyl-phenyl)-lH-pyrrol-2-yl] -butyric acid (all following Method 8). This material was coupled to 4S-amino-5-(2-oxo-pyrrolidin-3S-yl)-pent-2(trans)-enoic acid ethyl ester hydrochloride according to the procedure described in Method 3 of Example 31. Η NMR (CDC1 3 ) δ 10.01 (IH, br s), 7.72 (IH, d, J = 7.7), 7.55-7.40 (3H, m), 7.34- 7.16 (5H, m), 6.98 (IH, dd, J = 3.9, 2.4), 6.90 (IH, d, J - 7.4), 6.62 (IH, dd, J = 15.7, 5.1), 6.41 (IH, t, J = 3.2), 6.13 (IH, br s), 5.49 (IH, dd, J = 15.7, 1.6), 4.56-4.44 (IH, m), 4.16 (2H, q, J = 7.1), 3.39 (IH, dd, J = 16.1, 9.5), 3.25-2.96 (4H, m), 2.83-2.69 (2H, m), 2.42-2.28 (IH, m), 2.22-2.08 (IH, m), 1.94-1.78 (IH, m), 1.72-1.55 (IH, m), 1.52- 1.40 (IH, m), 1.30 (3H, t, J = 7.1). HRMS (MALDI) 610.2532 (MH + , calcd. 610.2529). Anal. (C 33 H 34 F 3 N 3 O 5 ) C, H, N. EXAMPLE 38 4S- {2R-Ethyl-4-oxo-4-[5-(2-trifluoromethyl-ρhenyl)- lH-pyrrol-2-yl]-butyrylamino} -5- (2-oxo-pyrrolidin-3S-yl)-pent-2(trans)-enoic acid ethyl ester. (Compound 37) 2R-Ethyl-N,N-dimethyl-succinamic acid methyl ester was prepared according to the procedure described in Example 8, starting with butyric acid. This was reacted with 2-(2-trifluoromethyl-phenyl)-lH-pyrrole (prepared according to the procedure described in Example 6), then demethylated to give 2R-ethyl-4-oxo-4-[5-(2-trifluoromethyl- phenyl)- lH-pyrrol-2-yl] -butyric acid (all following Method 8). This material was then coupled to 4S-amino-5-(2-oxo-pyrrolidin-3S-yl)-pent-2(trans)-enoic acid ethyl ester hydrochloride according to the procedure described in Method 3 of Example 31. l U NMR (CDC1 3 ) δ 10.13 (IH, br s), 7.76 (IH, d, J = 7.8), 7.62-7.46 (3H, m), 7.01 (IH, d, J = 3.9), 6.84 (IH, dd, J = 15.7, 5.2), 6.42 (IH, d, J = 3.9), 5.93 (IH, dd, J = 15.3, 1.6), 4.70-4.60 (IH, ), 4.17 (2H, q, J = 7.1), 3.36-3.15 (3H, m), 2.86-2.70 (2H, m), 2.58- 2.53 (IH, m), 2.33-2.23 (IH, m), 2.05-1.94 (IH, m), 1.83-1.74 (2H, m), 1.61-1.51 (2H, m), 1.27 (3H, t, J = 7.1), 1.01 (3H, t, J = 7.3). HRMS (MALDI) 548.2363 (MH 1" , calcd. 548.2372). Anal. (C 28 H 32 N 3 O 5 F 3 -0.7 H 2 O) C, H, N. EXAMPLE 39 4S-(2R-{2-[5-(2-Chloro-phenyl)-lH-ρyrrol-2-yl]-2-oxo-ethyl}-ρent-4-ynoylamino)-5- (2-oxo-pyrrolidin-3S-yl)-pent-2(trans)-enoic acid ethyl ester. (Compound 38) 2R-Dimethylcarbamoylmethyl-pent-4-ynoic acid methyl ester was prepared according to the procedure described in Example 8, starting with 4-pentynoic acid. This material was reacted with 2-(2-chloro-phenyl)-lH-pyrrole (prepared according to the procedure described in Example 6, starting with 2-chlorobenzaldehyde). This product was demethylated to give 2R-{2-[5-(2-chloro-phenyl)-lH-pyrrol-2-yι]-2-oxo- ethyl} -pent-4-ynoic acid (all following Method 8), then coupled to 4S-amino-5-(2-oxo- pyrrolidin-3S-yl)-pent-2(trans)-enoic acid ethyl ester hydrochloride according to the procedure described in Method 3 of Example 31. ΗNMR (CDC1 3 ) δ 10.58 (lH, br s), 7.65 (IH, d, J = 7.4), 7.56 (IH, dd, J = 7.6, 1.8), 7.46 (IH, dd, J = 7.7, 1.4), 7.37-7.23 (2H, m), 7.07 (IH, dd, J = 4.0, 2.4), 6.83 (IH, dd, J = 15.6, 4.7), 6.68 (IH, dd, J = 4.0, 2.6), 6.28 (IH, br s), 6.05 (IH, dd, J = 15.7, 1.6), 4.58-4.46 (IH, m), 4.15 (2H, q, J = 7.1), 3.38 (IH, dd, J = 15.3, 9.8), 3.15 (IH, t, J = 9.1), 3.10-2.95 (2H, m), 2.87 (IH, dd, J = 15.3, 3.7), 2.63 (IH, ddd, J = 16.8, 7.3, 2.6), 2.47 (IH, ddd, J = 16.8, 7.5, 2.6), 2.28- 2.15 (IH, m), 2.10 (IH, t, J = 2.5), 2.06-1.88 (2H, m), 1.73-1.50 (2H, m), 1.26 (3H, t, J = 7.1). HRMS (MALDI) 546.1750 (MNa + , calcd. 546.1722). Anal. (C 28 H 30 N 3 O 5 C1 -0.6 H 2 O) C, H, N. EXAMPLE 40 5-(2-Oxo-pyrrohdin-3S-yl)-4S-{2R-[2-oxo-2-(5-o-tolyl-lH-ρyrrol-2-yl)-ethyl]-pent-4- ynoylamino}-pent-2(trans)-enoic acid ethyl ester. (Compound 39) 2R-Dimethylcarbamoylmethyl-pent-4-ynoic acid methyl ester was prepared according to the procedure described in Example 8, starting with 4-pentynoic acid. This material was reacted with 2-(o-tolyl)-lH-pyrrole (prepared according to the procedure described in Example 5, starting with o-toluic acid). This product was demethylated to give 2R-[2-oxo-2-(5-o-tolyl-lH-pyrrol-2-yl)-ethyl]-pent-4-ynoic acid (all following Method 8), then coupled to 4S-amino-5-(2-oxo-pyrrolidin-3S-yl)-pent- 2(trans)-enoic acid ethyl ester hydrochloride according to the procedure described in Method 3 of Example 31. Η NMR (CDC1 3 ) δ 10.65 (IH, br s), 7.50 (IH, d, J = 7.6), 7.43-7.36 (IH, m), 7.30-7.21 (3H, m), 7.10-7.04 (IH, m), 6.82 (IH, dd, J = 15.6, 5.4), 6.47 (IH, br s), 6.39-6.33 (IH, m), 6.04 (IH, d, J = 15.6), 4.59-4.48 (IH, m), 4.15 (2H, q, J = 7.1), 3.39 (IH, dd, J = 15.4, 10.4), 3.12-2.95 (2H, m), 2.95-2.77 (2H, m), 2.68- 2.55 (IH, m), 2.51-2.38 (IH, m), 2.40 (3H, s), 2.36-2.25 (IH, m), 2.12 (IH, br s), 2.03- 1.90 (IH, m), 1.66-1.43 (2H, m), 1.26 (3H, t, J = 7.1). HRMS (MALDI) 504.2497 (MH*, calcd. 504.2498). Anal. (C 29 H 33 N 3 O 5 -0.7 H 2 O) C, H, N. EXAMPLE 41 4S-{2R-Benzyl-4-oxo-[5-(2-trifluoromethyl-phenyl)-lH-pyrrol-2-yl]-butyrylarrιino}-6- carbamoyl-hex-2(trans)-enoic acid ethyl ester. (Compound 40) 2R-Benzyl-N,N-dimethyl-succinamic acid (prepared according to the procedure described in Example 8, starting with hydrocinnamic acid) was reacted with 2-(2- trifluoromethyl-phenyl)-lH-pyrrole (prepared according to the procedure described in Example 6), then demethylated to give 2R-benzyl-4-oxo-4-[5-(2-trifluoromethyl- phenyl)- lH-pyrrol-2-yl] -butyric acid (all following Method 8), then coupled to Gln- resin, following Method 1. Η NMR (CD 3 OD) δ 7.70 (IH, d, J = 7.3), 7.58-7.41 (3H, m), 7.25-7.11 (5H, m), 6.95 (IH, d, J = 4.0), 6.53 (IH, dd, J = 15.8, 5.1), 6.35 (IH, d, J = 3.9) 5.38 (IH, dd, J = 15.8, 1.7), 4.47-4.38 (IH, m), 4.12 (2H, q, J = 7.1), 3.31 (IH, m), 3.08-2.70 (4H, m), 2.13 (2H, t, J = 7.9), 1.92-1.78 (IH, m), 1.63-1.50 (IH, m), 1.25 (3H, t, J = 7.1). HRMS (MALDI) 606.2194 (MNa + , calcd. 606.2192). EXAMPLE 42 4S-(4-oxo-pentanoylamino)-5-(2-oxo-pyrrolidin-3S-yl)-pent-2-enoic acid ethyl ester (Compound 43) 4S-Amino-5-(2-oxo-pyrrolidin-3S-yl)-pent-2-enoic acid ethyl ester (0.15 mmol, 35 mg) in DMF (1.5 ml) was treated with diisopropylethyl amine (0.30 mmol, 0.05 ml), 4-oxopentanoic acid (0.15 mmol, 27 mg), and HATU (0.15 mmol, 57 mg), and held at room temperature for 1 h. The solution was washed with brine (10 ml), and extracted with EtOAc (2x10 ml) and concentrated under reduced pressure to provide 40 mg of crude product. Purification by preparative reverse phase chromatography (CH 3 CN-H 2 O) provided 28 mg (48%) ofthe title product. Η NMR (CDC1 3 ) δ 7.28 (IH, s), 6.83 (IH, dd, J = 15.7, 5.2), 6.03 (IH, s), 5.92 (IH, dd, J = 15.7, 1.5), 4.65-4.50 (IH, m), 4.17 (2H, q, J = 7.1), 3.40-3.30 (2H, m), 2.92-2.65 (2H, m), 2.60-2.35 (4H, m), 2.17 (3H, m), 2.05-1.90 (IH, m), 1.90-1.72 (IH, m), 1.70-1.60 (IH, m), 1.27 (3H, t, J = 7.1). MS (ES) 347 (MNa + ), 323 (M-H) " . EXAMPLE 43 4S-(4-oxo-4-phenyl-butyrylamino)-5-(2-oxo-pyrrolidin-3 S-yl)-pent-2-enoic acid ethyl ester. (Compound 44) The title compound was prepared according to the method of Example 42, using 4-oxo-4-phenylbutyric acid. Η NMR (CDC1 3 ) δ 8.10-7.95 (2H, m), 7.60-7.53 (IH, m), 7.50-7.42 (2H, m), 6.86 (IH, dd, J = 15.6, 5.7), 5.97 (IH, d, J = 15.6), 5.73 (IH, s), 4.65-4.61 (IH, m), 4.19 (2H, q, J = 7.1), 3.50-3.20 (4H, m), 2.73-2.64 (2H, m), 2.62-2.35 (2H, m), 2.08-1.95 (IH, m), 1.92-1.65 (2H, m), 1.28 (3H, t, J = 7.1). MS (ES) 387 (MH*), 409 (MNa + ). EXAMPLE 44 4-S-(4-Naphthalen-l-yl-4-oxo-butyrylamino)-5-(2-oxo-pyrrolidin-3S-yl)-pent-2-enoic acid ethyl ester. (Compound 45) The title compound was prepared according to the method of Example 42, using as starting material gamma-oxo-1 -naphthalene butyric acid. 'HNMR (CDC1 3 ) δ 8.57 (IH, d, J = 8.6), 7.99-7.37 (7H, m), 6.88 (IH, dd, J = 15.6, 5.4), 6.05 (IH, s), 6.01 (lH,d, J = 15.6), 4.65-4.64 (IH, m), 4.17 (2H, q, J = 7.2), 3.57-3.27 (4H, m), 2.86-2.39 (4H, m), 2.09-1.66 (3H, m), 1.25 (3H, t, J = 7.2). MS (FAB) 437.2068 (MH + , calcd. 437.2076). EXAMPLE 45 4S-[2-(3-Chloro-phenylcarbamoyl)-acetylamino]-5-(2-oxo-pyrrolidin-3S-yl)- pent-2-enoic acid ethyl ester. (Compound 46) The title compound was prepared according to the method of Example 42, using as starting material N-(3-chloro-ρhenyl)-malonamic acid. X U NMR (CDC1 3 ) δ 9.89 (IH, s), 8.69 (IH, d, J = 6.1), 7.69 (IH, s), 7.41-7.36 (IH, m), 7.22 (IH, t, J = 8.1), 7.09-7.03 (IH, m), 6.84 (IH, dd, J = 15.7, 5.7), 5.96 (IH, d, J = 15.6), 5.97 (IH, s), 4.59-4.48 (IH, m), 4.18 (2H, q, J = 7.1), 3.43-3.34 (4H, m), 2.57-2.37 (2H, m), 2.06-1.80 (2H, m), 1.74 (IH, dt, J = 14.5, 4.3), 1.27 (3H, t, J = 7.1). MS (FAB) 422.1494 (MH 4 , calcd 422.1483), 444 (MNa + ). EXAMPLE 46 Preparation of Ethyl-3-{(Indole-2-carboxylic acid)-L-(4-F-Phe)-L-[(S)-Pyrrol-Ala]}- E-Propenoate. (Compound 42) hi this example, the following shorthand naming system employing amino acid abbreviations is used to identify some intermediates and final products. When naming compounds, italicized amino acid abbreviations represent modifications at the C- terminus of that residue where the following apply: (1) acrylic acid esters are reported as "E" (trans) propenoates; (2) substituted 3-methylene-dihydrofuran-2-ones are reported as "E" (trans) 2-(a-vinyl-g-butyrolactones); and (3) 5-vinylisoxazoles are reported as "E" (trans) propenisoxazoles. Ethyl-3-{Boc-L-(4-F-Phe)-L-[(N-2,4-Dimethoxybenzyl)-(S)-Pyrrol-Ala]}- E-Propenoate A solution of HCl in 1,4-dioxane (4.0 M, 12 ml) was added to a solution of ethyl-3- {Boc-L-[(N-2,4-dimethoxybenzyl)-(S)-Pyrrol-Ala] } -E-propenoate, prepared according to the procedure described in Dragovich, et al., J. Med. Chem. 1999, 42, 1213, (0.432 g, 0.906 mmol, 1 equiv) in the same solvent (12 ml). After stirring 1.5 h at 23 °C, the solvent was concentrated under reduced pressure to give the crude amine salt. This material was dissolved in DMF (7 ml) and cooled to 0 °C. Boc-L-(4-F-Phe)-OH (0.308 g, 1.09 mmol, 1.2 equiv), N,N-diisoproρylethylamine (0.474 ml, 2.72 mmol, 3 equiv) and HATU (0.379 g, 0.997 mmol, 1.1 equiv) were added sequentially and the reaction mixture was allowed to warm to 23 °C. After 1.5 h, the mixture was diluted with MTBE (200 ml), and washed with 5% KHSO4 and brine (20 ml each), dried over MgSO4 and concentrated. The residue was purified by flash column chromatography (60% EtOAc in hexanes) to provide ethyl-3-{Boc-L-(4-F-Phe)-L-[(N-2,4- dimethoxybenzyl)-(S)-Pyrrol-Ala]} -E-propenoate (0.447 g, 77%) as a white foam: Rf = 0.34 (60% EtOAc in hexanes); IR (cm" 1 ) 3258, 1705, 1666; Ϊ H NMR (CDC13) δ 1.28 (t, 3H, J = 7.2), 1.45 (s, 9H), 1.51-1.66 (m, 2H), 1.78-1.90 (m, IH), 2.06-2.23 (m, 2H), 2.99 (dd, IH, J = 13.7, 6.2), 3.11 (dd, IH, J = 13.7, 5.3), 3.17-3.23 (m, 2H), 3.80 (s, 3H), 3.81 (s, 3H), 4.18 (q, 2H, J = 7.2), 4.35 (s, 2H), 4.38-4.51 (m, 2H), 5.29-5.37 (m, IH), 5.76 (d, IH, J = 15.8), 6.43-6.47 (m, 2H), 6.72 (dd, IH, J = 15.8, 5.3), 6.83-6.91 (m, 2H), 7.09-7.17 (m, 3H), 7.92 (br, IH); Anal. (C34H44FN3O8) C, H, N. Preparation of Intermediate Ethyl-3-{Boc-L-(4-F-Phe)-L-[(S)-Pyrrol-Ala]}- E-Propenoate 2,3-Dicholoro-5,6-dicyano-l,4-benzoquinone (0.14 g, 0.62 mmol, 1 equiv) was added to a solution of ethyl-3- {Boc-L-(4-F-Phe)-L-[(N-2,4-dimethoxybenzyl)-(S)- pyrrol-Ala]} -E-propenoate (0.39 g, 0.53 mmol, 1 equiv) in CHCI3 (25 ml) and water (2.5 ml) and the reaction mixture was heated to reflux at 60 °C. After 2 h, an additional equivalent of 2,3-dichloro-5,6-dicyano-l,4-benzoquinone was added to the mixture. After 2 h, one more equivalent of 2,3-dichloro-5,6-dicyano-l,4-benzoquinone was added to the mixture. The reaction mixture was diluted with EtOAc (150 ml) and washed sequentially with NaHCO3 (100 ml) and brine (100 ml). The organic layers were dried over Na2SO4, concentrated, and the residue was purified by flash column chromatography (2% CH3OH in CH2CI2) to afford ethyl-3- {Boc-L-(4-F-Phe)-L- [(S)-pyrrol-Ala]} -E-propenoate (0.205 g, 79%) as a white solid: Rf = 0.18 (5% CH3OH in CH2CI2); IR (cm" 1 ) 3281, 2981, 1690; iHNMR (CDCI3) δ 1.27-1.31 (t, 3H, J = 7.2), 1.42 (s, 9H), 1.57-1.64 (m, IH), 1.75-1.94 (m, 2H), 2.23-2.36 (m, 2H), 3.01-3.05 (m, 2H), 3.29-3.34 (m, 2H), 4.18 (q, 2H, J = 7.2), 4.42-4.50 (m, 2H), 5.23 (m, IH), 5.69-5.79 (m, 2H), 6.69-6.74 (m, IH), 6.94-7.00 (m, IH), 7.14-7.18 (m, 2H), 7.43 (m, IH); Anal. Calcd for C25H34FN3O6-0.5H2O C, 59.99; H, 7.05; N, 8.39. Found C, 59.63; H, 7.05; N, 8.14. Ethyl-3- {(Indole-2-carboxylic acid)-L-(4-F-Phe)-L-[(S)-Pyrrol-Ala] } -E-Propenoate A solution of HCl in 1,4-dioxane (4.0 M, 2 ml) was added to ethyl-3- {Boc-L- (4-F-Phe)-L-[(S)-ρyrrol-Ala]}-E-proρenoate (0.19 g, 0.39 mmol, 1 equiv) in 2 ml of 1,4-dioxane at 23 °C. After 2 h, the volatiles were removed under reduced pressure and CH2CI2 (3 ml) and Et3N (1 ml) were added sequentially to the residue. In a separate flask, N-hydroxysuccinimide (0.075 g, 0.65 mmol, 1.1 equiv) and 1,3-dicyclohexylcarbodiimide (0.13 g, 0.64 mmol, 1.1 equiv) were added to a solution of indole-2-carboxylic acid (0.99 g, 0.62 mmol, 1 equiv) in CH2CI2 (3 ml) and DMF (1 ml) and stirred at 23 °C for 3 h. This solution was then filtered and added to the original reaction mixture described above. The resulting solution was stirred at 23 °C for 16 h. then was partitioned between water (25 ml) and CH2CI2 (2 x 20 ml). The combined organic layers were dried over Na2SO4, concentrated, and the residue was purified by flash column chromatography (1 to 5 % CH3OH in CH2CI2) to afford ethyl-3- {(indole-2-carboxylic acid)-L-(4-F-Phe)-L-[(S)-pyrrol-Ala] } -E-propenoate (0.145 g, 70%) as a white powder: Rf = 0.44 (10% CH3OH in CH2CI2); IR (cm" 1 ) 3277, 1636, 1547; 1H NMR (DMSO-d6) δ 1.28 (t, 3H, J = 7.2), 1.51-1.59 (m, IH), 1.66-1.73 (m, IH), 1.89-1.96 (m, IH), 2.10-2.18 (m, IH), 2.39-2.42 (m, IH), 3.09-3.17 (m, 4H), 4.18 (q, 2H, J = 7.5), 4.62 (m, IH), 4.75-4.77 (m, IH), 5.71-5.82 (m, IH), 6.87 (dd, IH, J = 4.2, 15.9), 7.07-7.17 (m, 3H), 7.21-7.26 (m, 3H), 7.42-7.47 (m, 3H), 7.66-7.70 (m, 2H), 8.45 (d, IH, J = 8.7), 8.72 (d, IH, J = 7.8); Anal. Calcd for C29H31FN4O5O.35 H2O: C, 64.40; H, 5.91; N, 10.36. Found C, 64.12; H, 5.91; N, 10.14. Results of tests conducted using exemplary compounds ofthe invention are described below. BIOCHEMICAL AND BIOLOGICAL EVALUATION Inhibition of Rhinovirus 3C Protease: Stock solutions (50 mM, in DMSO) of various compounds were prepared; dilutions were in the same solvent. Recombinant rhinovirus 3C proteases (see Birch et al., "Purification of recombinant human rhinovirus 14 3C protease expressed in Escherichia coli," Protein Expr. Pur. (1995), vol. 6(5), 609-618) from serotypes 14, 16, and 2 were prepared by the following standard chromatographic procedures: (1) ion exchange using Q Sepharose Fast Flow from Pharmacia; (2) affinity chromatography using Affi-Gel Blue from Biorad; and (3) sizing using Sephadex G- 100 from Pharmacia. Each assay sample contained 2% DMSO, 50 mM tris pH 7.6, 1 mM EDTA, a test compound at the indicated concentration, approximately 1 μM substrate, and 50-100 nM protease. The k D bs/I values were obtained from reactions initiated by addition of enzyme rather than substrate. RVP activity was measured in the fluorescence resonance energy transfer assay. The substrate was (N-terminal) DABCYX-(Gly-Arg-Ala-Nal-Phe-Gln-Gly-Pro-Val-Gly)-EDANS. In the uncleaved peptide, the EDANS fluorescence was quenched by the proximal DABCYL moiety. When the peptide was cleaved, the quenching was relieved, and activity was measured as an increase in fluorescence signal. Data were analyzed using standard non-linear fitting programs (Enzfit), and are shown in the table below. The tabulated data in the column designated k obs /[I] were measured from progress curves in enzyme start experiments. Antirhino viral Hl-HeLa Cell Culture Assay: In this cell protection assay, the ability of compounds to protect cells against HRV infection was measured by the XTT dye reduction method, which is described in Weislow et al., J. Natl. Cancer hist. (1989), vol. 81, 577-586. Hl-HeLa cells were infected with HRV-14 at a multiplicity of infection (m.o.i.) of 0.13 (viras particles/cell) or mock-infected with medium only. Infected or mock-infected cells were resuspended at 8 x 10^ cells per ml, and incubated with appropriate concentrations ofthe compounds to be tested. Two days later, XTT/PMS was added to test plates and the amount of formazan produced was quantified spectrophotometrically at 450/650 nm. The EC50 value was calculated as the concentration of compound that increased the percentage of formazan production in compound-treated, viras-infected cells to 50% of that produced by compound-free, mock-infected cells. The 50% cytotoxic dose (CC50) was calculated as the concentration of compound that decreased the percentage of formazan produced in compound-treated, mock-infected cells to 50% of that produced by compound-free, mock-infected cells. The therapeutic index (TI) was calculated by dividing the CC50 value by the EC50 value. All strains of human rhinovirus (HRV) for use in this assay were purchased from American Type Culture Collection (ATCC), except for HRV serotype-14 (produced from the infectious cDNA clone constructed by Dr. Robert Rueckert, Institute for Molecular Virology, University of Wisconsin, Madison, Wisconsin). HRV stocks were propagated and viral assays were performed in Hl-HeLa cells (ATCC). Cells were grown in minimal essential medium with 10% fetal bovine serum, available from Life Technologies (Gaithersburg, MD). Test results for the HRV assay are shown in the table below. Anticoxsackieviral Cell Culture Assay: Coxsackievirus types A-21 (CAV-21) and B3 (CVB3) were purchased from American Type Culture Collection (ATCC, Rockville, MD). Viras stocks were propagated and antiviral assays were performed in Hl-HeLa cells (ATCC). Cells were grown in minimal essential medium with 10% fetal bovine serum (Life Technologies, Gaithersburg, MD). The ability ofthe compounds of this invention to protect cells against either CAV-21 or CVB3 infection was measured by the XTT dye reduction method. This method is described in Weislow et al., J. Natl. Cancer List. (1989), vol. 81, 577-586. Hl-HeLa cells were infected with CAV-21 or CVB3 at a multiplicity of infection (m.o.i.) of 0.025 or 0.075, respectively, or mock-infected with medium only. Hl-HeLa cells were plated at 4 x 10^ cells per well in a 96-well plate and incubated with appropriate concentrations ofthe test compound. One day (CVB3) or two days (CAV-21) later, XTT/PMS was added to test plates and the amount of formazan produced was quantified spectrophotometrically at 450/650 nm. The EC50 was calculated as the concentration of compound that increased the formazan production in compound-treated, virus-infected cells to 50% of that produced by compound-free, uninfected cells. The 50% cytotoxic dose (CC50) was calculated as the concentration of compound that decreased formazan production in compound-treated, uninfected cells to 50% of that produced in compound-free, uninfected cells. The therapeutic index (TI) was calculated by dividing the CC50 by the EC50. Anti-Echo viral and Anti-Entero viral Cell Culture Assays: Echovirus type 11 (ECHO 11) was purchased from ATCC (Rockville, MD). Viras stocks were propagated and antiviral assays were performed in MRC-5 cells (ATCC). Cells were grown in minimal essential medium with 10% fetal bovine serum (Life Technologies, Gaithersburg, MD). The ability ofthe compounds of this invention to protect cells against ECHO 11 infection was measured by the XTT dye reduction method (Weislow et al., J. Natl. Cancer hist. (1989), vol. 81, 577-586). MRC-5 cells were infected with ECHO 11 at an m.o.i. of 0.003 or 0.004, respectively, or mock-infected with medium only. Infected or uninfected cells were added at 1 x 10^ cells per well and incubated with appropriate concentrations of compound. Four days later, XTT/PMS was added to test plates, and the amount of formazan produced was quantified spectrophotometrically at 450/650 nm. The EC50 was calculated as the concentration of compound that increased the formazan production in compound-treated, viras-infected cells to 50% of that produced by compound-free, uninfected cells. The 50% cytotoxic dose (CC50) was calculated as the concentration of compound that decreased formazan production in compound-treated, uninfected cells to 50% of that produced in compound-free, uninfected cells. The therapeutic index (TI) was calculated by dividing the CC50 by the EC50. Activity ofthe compounds against enterovirus type 70 (EV 70) may be measured by the same assay as described above in this section. Enterovirus type 70 (EV 70) may be obtained from the American Type Culture Collection ATCC (Rockville, MD). Antiviral data obtained for the test compounds are shown in the table below. The designation "ND" indicates that a value was not determined for that compound, and the designation "NA" means not applicable. *. > U-> t t o o Ux o u> Ux While the invention has been described in terms of preferred embodiments and specific examples, those skilled in the art will recognize through routine experimentation that various changes and modifications can be made without departing from the spirit and scope ofthe invention. Thus, the invention should be understood as not being limited by the foregoing detailed description, but as being defined by the appended claims and their equivalents. .

Claims: WE CLAIM: 1. An antipicornaviral compound having the formula: wherein: R a is an alkylcarbonylalkyl, cycloalkylcarbonylalkyl, arylcarbonylalkyl, heteroarylcarbonylalkyl, alkylcarbonylaminoalkyl, cycloalkylcarbonylaminoalkyl, heterocycloalkylcarbonylaminoalkyl, arylcarbonylaminoalkyl, heteroarylcarbonylaminoalkyl, alkylammocarbonylalkyl, cycloalkylaminocarbonylalkyl, heterocycloalkylaminocarbonylalkyl, arylaminocarbonylalkyl, heteroarylaminocarbonylalkyl group, where each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl moiety thereof may be unsubstituted or substituted with one or more suitable substituents; R b is H or an alkyl group, unsubstituted or substituted with one or more suitable substituents; R d is H, halo, hydroxyl, or an alkyl, alkoxy or alkylthio group, where the alkyl, alkoxy or alkylthio group is unsubstituted or substituted with one or more suitable substituents; R° is a moiety having the formula: R e and R f are each independently H or a lower alkyl group; m is 0 or 1, provided that when m is 1, R a is not an amino-substituted alkylcarbonylalkyl or amino-substituted alkylcarbonylaminoalkyl group, and when m is 0, R a is selected from an alkylammocarbonylalkyl, cycloalkylaminocarbonylalkyl, heterocycloalkylaminocarbonylalkyl, arylaminocarbonylalkyl, heteroarylaminocarbonylalkyl and heteroarylcarbonylaminoalkyl group, provided that R is not substituted indolecarbonylaminoalkyl; p is an integer of from 0 to 5; when p is 1, 2, 3, 4, or 5, A 2 is C(R ε )(R h ), N(R j ), S, S(O), S(O) 2 , or O, and when p is 0, A 2 is C(R ε )(R h )(R i ), NCR 8 )^ 1 ), S(R g ), S(O)(R , S(O) 2 (R g ), or OCR 8 ), where each R g , R h and R is independently H or a lower alkyl group; each A 3 present is independently C(R ε )(R h ), N(R), S, S(O), S(O) 2 , or O, where each R s , R h and R 1 is independently H or a lower alkyl group; when p is 1, 2, 3, 4, or 5, A 4 is N(R j ), C(R )(R h ), or O, and when p is 0, A 4 is NCR/XR"), C(R 8 )(R h )(R i ), and OCR"), where each R ε , R h and R is independently H or a lower alkyl group, each R j is H, an alkyl, aryl, or acyl group, and each R k is H or an alkyl or aryl group; provided that no more than two heteroatoms occur consecutively in the above-depicted ring formed by A l5 (A 2 ) m , (A 3 ) p , A 4 , and C=O, where each dotted line in the ring depicts a single bond when A 2 is present and a hydrogen atom when A 2 is absent; and Z and Z 1 are each independently H, F, an alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl group, where the alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl group is unsubstituted or substituted with one or more suitable substituents, -C^R 1 , -CO^ 1 , -CN, -C(0)m}R m , -C(0)NR}OR m , -C(S)R l , -C(S)OR' -C(S)NR 1 R m , -C(=NR 1 )R m , -C(=NR 1 )OR m , -NO 2 , -SOR m , -SO.R 1 , -SO^R" 1 , -SO 2 (NR')(OR m ), -SONR 1 , -SO 3 R\ -PO(OR') 2 , -PO^R^OR 111 ) , -PO(NR 1 R m )(OR n ) ; -PO(NR 1 R m )(NR n R°), -Cf NR'NR"^, -C(S)NR 1 NR m R n , where R 1 , R m , R n and R° are each independently H or an alkyl, cycloalkyl, aryl, heterocycloalkyl, acyl or thioacyl group, where the alkyl, cycloalkyl, aryl, heterocycloalkyl, acyl or thioacyl group is unsubstituted or substituted with one or more suitable substituents, or where any two ofthe R 1 , R ra , R n and R°, taken together with the atoms to which they are bonded, form a heterocycloalkyl group, which may be optionally substituted, or Z and R d , together with the atoms to which they are bonded, form a cycloalkyl or heterocycloalkyl group, where Z and R d are as defined above except for moieties that cannot form the cycloalkyl or heterocycloalkyl group, or Z and Z 1 , together with the atoms to which they are bonded, form a cycloalkyl or heterocycloalkyl group, where Z and Z 1 are as defined above; or a prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate of said compound. 2. The compound according to claim 1, wherein A 2 is C(R ε )(R h ), N(R), S, S(O), S(O) 2 , or O, where each R ε , R h and R 1 is independently H or a lower alkyl group; each A 3 present is independently C(R g )(R h ), N(R ! ), S, S(O), S(O) 2 , or-O, where each R ε , R h and R 1 is independently H or a lower alkyl group; when p is 1, 2, 3, 4, or 5, A 4 is N(R j ), C(R ε )(R h ), or O, and when p is 0, A 4 is NCR^CR"), C(R s )(R h )(R i ), and O(R k ), where each R g , R h and R? is independently H or a lower alkyl group, each R J is H, an alkyl, aryl, or acyl group, and each R k is H or an alkyl or aryl group; provided that no more than two heteroatoms occur consecutively in the above-depicted ring formed by A l5 (A 2 ) m , (A 3 ) p , A 4 , and C=O, where each dotted line in the ring depicts a single bond when A 2 is present and a hydrogen atom when A 2 is absent; and Z and Z 1 are each independently H, F, an alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl group, where the alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl group is unsubstituted or substituted with one or more suitable substituents, -C(O)R\ -COaR 1 , -CN, -C^NR' ", -C^NR'OR™, -C(β)BL l , -C(S)NR'R m , -NO 2 , -SOR m , -SO.R 1 , -SO.NR'R" 1 , -SO 2 (NR I )(OR m ), -SONR 1 , -SO j R 1 , -PO(OR') 2 , -PO(NR 1 R ra )(NR n R°), -C(O)NR 1 NR ra R", -C(S)NR I NR m R n , where R 1 , R m , R n and R° are each independently H, an alkyl, cycloalkyl, aryl, heterocycloalkyl, acyl or thioacyl group, where the alkyl, cycloalkyl, aryl, heterocycloalkyl, acyl or thioacyl group is unsubstituted or substituted with one or more suitable substituents, or where any two ofthe R 1 , R m , R n and R°, taken together with the atoms to which they are bonded, form a heterocycloalkyl group, which is unsubstituted or substituted with one or more suitable substituents, or Z and Z 1 , together with the atoms to which they are bonded, form a cycloalkyl or heterocycloalkyl group, where Z and Z 1 are as defined above. 3. The compound according to claim 1 or 2, having the formula: wherein R a ' is an alkyl, cycloalkyl, aryl or heteroaryl group, where said alkyl, cycloalkyl, aryl or heteroaryl group is unsubstituted or substituted with one or more suitable substituents, n is 1, 2 or 3, m is 1, R x and R y are each independently selected from H and an alkyl group, unsubstituted or substituted with one or more suitable substituents, and R , R c , R d , Z and Z 1 are as defined in claim 1 or 2, respectively, provided that R a ' is not an amino-substituted alkyl group. 4. The compound according to claim 1 or 2, having the formula: wherein R a' is an alkyl, cycloalkyl, aryl or heteroaryl group, where said alkyl, cycloalkyl, aryl or heteroaryl group is unsubstituted or substituted with one or more suitable substituents, n is 1, 2 or 3, m is 1, R x and R y are each independently selected from H and an alkyl group, unsubstituted or substituted with one or more suitable substituents, and R , R c , R d , Z and Z 1 are as defined in claiml or 2, respectively, provided that R a ' is not an amino-substituted alkyl group. The compound according to claim 1 or 2, having the formula: wherein R a ' is an alkyl, aryl, cycloalkyl, heterocycloalkyl or heteroaryl group, where said alkyl, aryl, cycloalkyl, heterocycloalkyl and heteroaryl group is unsubstituted or substituted with one or more suitable substituents, n is 1, 2 or 3, R x and R y are each independently selected from H and an alkyl group, unsubstituted or substituted with one or more suitable substituents, and R , R c , R d , Z and Z 1 are as defined as in claim 1 or 2, respectively. 6. The compound according to claim 1 or 2, wherein said substituted alkyl, aryl, cycloalkyl, heterocycloalkyl or heteroaryl comprises one or more substituents independently selected from an alkyl, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, nitro, amino, cyano, halo, hydroxyl, alkoxy, aUcylenedioxy, aryloxy, cycloalkoxy, heterocycloalkoxy, heteroaryloxy, alkylcarbonyl, alkyloxycarbonyl, alkylcarbonyloxy, arylcarbonyl, arylcarbonyloxy, aryloxycarbonyl, cycloalkylcarbonyl, cycloalkylcarbonyloxy, cycloalkyoxycarbonyl, heteroarylcarbonyl, heteroarylcarbonyloxy, heteroaryloxycarbonyl, heterocycloalkylcarbonyl, heterocycloalkylcarbonyloxy, heterocycloalkyoxycarbonyl, carboxyl, carbamoyl, formyl, keto, thioketo, sulfo, alkylamino, cycloalkylamino, arylamino, heterocycloalkylamino, heteroarylamino, dialkylamino, alkylaminocarbonyl, cycloalkylaminocarbonyl, arylaminocarbonyl, heterocycloalkylaminocarbonyl, heteroarylaminocarbonyl, dialkylaminocarbonyl, alkylaminothiocarbonyl, cycloalkylaminotbiocarbonyl, arylaminothiocarbonyl, heterocycloalkylaminothiocarbonyl, heieroarylammothiocarbonyl, dialkylaminothiocarbonyl, alkylsulfonyl, arylsulfonyl, alkylsulfenyl, arylsulfenyl, alkylcarbonylamino, cycloalkylcarbonylamino, arylcarbonylamino, heterocycloalkylcarbonylamino, heteroarylcarbonylamino, alkylthiocarbonylamino, cycloalkylthiocarbonylamino, aryltMocarbonylamino, heterocycloalkylthiocarbonylamino, heteroarylthiocarbonylamino, alkylsulfonyloxy, arylsulfonyloxy, alkylsulfonylamino, arylsulfonylamino, mercapto, alkylthio, arylthio and heteroarylthio group, where any ofthe alkyl, alkylene, aryl, cycloalkyl, heterocycloalkyl, heteroaryl moieties present in the above substituents may be further substituted with one or more suitable substituents. 7. The compound according to claim 6, wherein said substituted alkyl, alkylene, aryl, cycloalkyl, heterocycloalkyl, heteroaryl moieties may be further substituted with one or more substituents selected from nitro, amino, cyano, halo, haloalkyl, haloaryl, hydroxyl, keto, hydroxamino, alkylamino, dialkylamino, mercapto, and unsubstituted alkyl, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, alkoxy, aryloxy, alkylthio or arylthio groups and wherein any ofthe aryl or heteroaryl moieties may be substituted with alkylenedioxy. 8. An antipicornaviral compound having the formula: wherein: W is CH orN; R a ' is an alkyl, cycloalkyl, aryl or heteroaryl group, where said alkyl, cycloalkyl, aryl, and heteroaryl group is unsubstituted or substituted with one or more suitable substituents, provided that R a ' is not an amino-substituted alkyl group; R 4 and R 6 are each independently H or a lower alkyl group; R 5 is H or an alkyl group; R 7 is a moiety having the formula: wherein: R 8 and R 9 are each mdependently H or lower alkyl; p is an integer of from 1 to 5; when p is 1, 2, 3, 4, or 5, A 2 is C(R 10 )(R n ), N(R 12 ), S, S(O), S(O) 2 , or O, and when p is 0, A 2 is C(R 10 )(R U )(R 12 ), N(R 10 )(R 12 ), S(R 10 ), S(O)(R 10 ), S(O) 2 (R 10 ), or O(R 10 ) where each R 10 , R 11 and R 12 is independently H or a lower alkyl group; each A 3 present is independently C(R 10 )(R U ), N(R 12 ), S, S(O), S(O) 2 , or O, where each R 10 , R 11 and R 12 is independently H or a lower alkyl group; when p is 1, 2, 3, 4, or 5, A 4 is N(R 13 ), C(R 10 )(R n ), or O, and when p is 0, A 4 is N(R 13 )(R 14 ), C(R 10 )(R n )(R 12 ), and O(R 14 ), where each R 10 , R 11 and R 12 is independently H or a lower alkyl group, each R 13 is H or an alkyl, aryl, or acyl group, and each R 14 is H or an alkyl or aryl group; provided that no more than two heteroatoms occur consecutively in the above-depicted ring formed by A l5 (A 2 ) m , (A 3 ) p , A 4 , and C=O, where each dotted line in the ring depicts a single bond when A 2 is present and a hydrogen atom when A 2 is absent; and Z and Z 1 are each independently H, F, an alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl group, where the alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl group is unsubstituted or substituted with one or more suitable substituents, -C(O)R 15 , -CO 2 R 15 , -CN, -C(O)NR 15 R 16 , -C(O)NR I5 OR 16 , -C(S)R 15 , -C(S)OR 15 , -C(S)NR 15 R 16 , -C(=NR 15 )R 16 , -C(=NR 15 )OR 16 , -NO 2 , -SOR 16 , -SO 2 R 15 , -SO 2 NR 15 R 16 , -SO 2 (NR 15 )(OR 16 ), -SONR 15 , -SO 3 R 15 , -PO(OR 15 ) 2 , -PO(OR 15 )(OR 16 ) , -PO(NR 15 R 16 )(OR 17 ) ; -PO(NR 15 R 16 )(NR 17 R 18 ), -C(O)NR 15 NR 16 R 17 , -C(S)NR 15 NR 16 R 17 , where R 15 , R 16 , R 17 and R 18 are each independently H or an alkyl, cycloalkyl, aryl, heterocycloalkyl, acyl or thioacyl group, where the alkyl, cycloalkyl, aryl, heterocycloalkyl, acyl or thioacyl group is unsubstituted or substituted with one or more suitable substituents, or where any two ofthe R 15 , R 16 , R 17 and R 18 , taken together with the atoms to which they are bonded, form a heterocycloalkyl group, which is unsubstituted or substituted with one or more suitable substituents, or Z and Z 1 , together with the atoms to wliich they are bonded, form a cycloalkyl or heterocycloalkyl group, where Z and Z 1 are as defined above; or a prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate of said compound. 9. The compound according to claim 8, wherein: A 2 is C(R 10 )(R U ), N(R 12 ), S, S(O), S(O) 2 , or O, where each R 10 , R 11 and R 12 is independently H or a lower alkyl group; each A 3 present is independently C(R 10 )(R U ), N(R 12 ), S, S(O), S(O) 2 , or O, where each R 10 , R 11 and R 12 is independently H or a lower alkyl group; when p is 1, 2, 3, 4, or 5, A 4 is N(R 13 ), C(R 10 )(R n ), or O, and when p is 0, A 4 is N(R I3 )(R 14 ), C(R 10 )(R n )(R 12 ), and O(R 14 ), where each R 10 , R" and R 12 is independently H or a lower alkyl group, each R 13 is H or an alkyl, aryl, or acyl group, and each R 14 is H or an alkyl or aryl group; provided that no more than two heteroatoms occur consecutively in the above-depicted ring formed by A l5 (A 2 ) m , (A 3 ) p , A 4 , and C=O, where each dotted line in the ring depicts a single bond when A 2 is present and a hydrogen atom when A 2 is absent; and Z and Z 1 are each independently H, F, an alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl group, where the alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl group is unsubstituted or substituted with one or more suitable substituents, -C(O)R 15 , -CO 2 R 15 , -CN, -C(O)NR 15 R 16 , -C(O)NR 15 OR 16 , -C(S)R 15 , -C(S)NR 15 R 16 , -NO 2 , -SOR 16 , -SO 2 R 15 , -SO 2 NR 15 R 16 , -SO 2 (NR 15 )(OR 16 ), -SONR 15 , -SO 3 R 15 , -PO(OR 15 ) 2 , -PO(OR 15 )(OR 16 ) ; -PO(NR 15 R 16 )(OR 17 ) ; -PO(NR 15 R 16 )(NR 17 R 18 ), -C(O)NR 15 NR 16 R 17 , -C(S)NR 15 NR 16 R 17 , where R 15 , R 16 , R 17 and R 18 are each independently H or an alkyl, cycloalkyl, aryl, heterocycloalkyl, acyl or thioacyl group, where the alkyl, cycloalkyl, aryl, heterocycloalkyl, acyl or thioacyl group is unsubstituted or substituted with one or more suitable substituents, or where any two of the R 15 , R 16 , R 17 and R 18 , taken together with the atoms to which they are bonded, form a heterocycloalkyl group, which is unsubstituted or substituted with one or more suitable substituents, or Z and 7), together with the atoms to which they are bonded, form a cycloalkyl or heterocycloaUcyl group, where Z and Z 1 are as defined above. 10. The compound according to claim 8 or 9, having the formula: wherein R ' is an alkyl, cycloaUcyl, aryl or heteroaryl group, where said alkyl, cycloaUcyl, aryl, and heteroaryl group is unsubstituted or substituted with one or more suitable substituents, and R 4 , R 5 , R 6 , R 7 , Z and Z 1 are defined as in claim 8 or 9, respectively, provided that R a ' is not amino-substituted alkyl. 11. The compound according to claim 8 or 9, having the formula: wherein R a ' is an alkyl, cycloalkyl, aryl or heteroaryl group, where said alkyl, cycloaUcyl, aryl, and heteroaryl group is unsubstituted or substituted with one or more suitable substituents, and R 4 , R 5 , R 6 , R 7 , Z and Z 1 are defined as in claims 8 or 9, repsectively, provided that R a' is not amino-substituted alkyl. 12. An antipicornaviral compound having the formula: wherein: R 1 is H, halo or an alkoxy, alkyl, aryl, cycloaUcyl, heterocycloalkyl or heteroaryl group, where the alkoxy, alkyl,cycloalkyl, heterocycloaUcyl or heteroaryl group is unsubstituted or substituted with one or more suitable substituents; R 2 and R 3 are each independently H, halo or an alkoxy or lower alkyl group, where the alkoxy or lower alkyl group is unsubstituted or substituted with one or more suitable substituents; or R 1 together with R 2 form a cycloalkyl, heterocycloalkyl, aryl or heteroaryl ring, where the cycloaUcyl, heterocycloaUcyl, aryl or heteroaryl ring is unsubstituted or substituted with one or more suitable substituents; R 4 and R 6 are each independently H or a lower alkyl group, unsubstituted or substituted with one or more suitable substituents; R 5 is H or an alkyl group, unsubstituted or substituted with one or more suitable substituents; R 7 is a moiety having the formula: wherein: R 8 and R 9 are each independently H or a lower alkyl group; m is O or 1; p is an integer of from 0 to 5; when p is 1, 2, 3, 4, or 5, A 2 is C(R 10 )(R π ), N(R 12 ), S, S(O), S(O) 2 , or O, and when p is 0, A 2 is C(R 10 )(R U )(R 12 ), N(R 10 )(R 12 ), S(R 10 ), S(O)(R 10 ), S(O) 2 (R 10 ), or O(R 10 ) where each R 10 , R u and R 12 is independently H or a lower alkyl group; each A 3 present is independently CQR. 10 )^ 11 ), N(R 12 ), S, S(O), S(O) 2 , or O, where each R 10 , R 11 and R 12 is mdependently H or a lower alkyl group; when p is 1, 2, 3, 4, or 5, A 4 is N(R 13 ), C(R 10 )(R n ), or O, and when p is 0, A 4 is N(R 13 )(R 14 ), C R- 10 )^ 11 )^ 12 ), and O(R 14 ), where each R 10 , R 11 and R 12 is each independently H or a lower alkyl group, each R 13 is H or an alkyl, aryl, or acyl group, and each R 14 is H or an alkyl or aryl group; provided that no more than two heteroatoms occur consecutively in the above-depicted ring formed by A l5 (A 2 ) m , (A 3 ) p , A 4 , and C=O, where each dotted line in the ring depicts a single bond when A 2 is present and a hydrogen atom when A 2 is absent; and Z and Z 1 are each independently H, F, an alkyl, cycloaUcyl, heterocycloaUcyl, aryl or heteroaryl group, where the alkyl, cycloaUcyl, heterocycloaUcyl, aryl or heteroaryl group is unsubstituted or substituted with one or more suitable substituents, -C(O)R 15 , -CO 2 R 15 , -CN, -C(O)NR 15 R 16 , -C(O)NR 15 OR 16 , -C(S)R 15 , -C(S)OR 15 , -C(S)NR 15 R 16 , -C(=NR 15 )R 16 , -C(=NR 15 )OR 16 , -NO 2 , -SOR 16 , -SO 2 R 15 , -SO 2 NR 15 R 16 , -SO 2 (NR 15 )(OR 16 ), -SONR 15 , -SO 3 R 15 , -PO(OR 15 ) 2 , -PO(NR 15 R 16 )(OR 17 ) , -PO(NR 15 R 16 )(NR ,7 R 18 ), -C(O)NR ,5 NR 16 R 17 , -C(S)NR 15 NR 16 R 17 , where R 15 , R 16 , R 17 and R 18 are each independently H or an alkyl, cycloaUcyl, aryl, heterocycloaUcyl, acyl or thioacyl group, where the alkyl, cycloaUcyl, aryl, heterocycloaUcyl, acyl or thioacyl group is unsubstituted or substituted with one or more suitable substituents, or where any two ofthe R 15 , R 16 , R 17 and R 18 , taken together with the atoms to which they are bonded, form a heterocycloaUcyl group, which is unsubstituted or substituted with one or more suitable substituents, or Z and Z 1 , together with the atoms to which they are bonded, form a cycloaUcyl or heterocycloaUcyl group, where Z and Z 1 are as defined above; or a prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate thereof of said compound. 13. An antipicornaviral compound having the formula: wherein: R 1 is H, halo or an alkoxy, alkyl, aryl, cycloaUcyl, heterocycloalkyl, or heteroaryl group, where the alkoxy, alkyLcycloalkyl, heterocycloaUcyl or heteroaryl group is unsubstituted or substituted with one or more suitable substituents; R 2 and R 3 are each independently H, halo or an alkoxy or lower alkyl group, where the alkoxy or lower alkyl group is unsubstituted or substituted with one or more suitable substituents; or R 1 together with R 2 form a cycloaUcyl, heterocycloaUcyl, aryl or heteroaryl ring, where the cycloaUcyl, heterocycloaUcyl, aryl or heteroaryl ring is unsubstituted or substituted with one or more suitable substituents; R 4 and R 6 are each independently H or a lower alkyl group, unsubstituted or substituted with one or more suitable substituents; R 5 is H or an alkyl group, unsubstituted or substituted with one or more suitable substituents; R 7 is a moiety having the formula: wherein: R 8 and R 9 are each independently H or a lower alkyl group; m is 0 or 1 , provided that when m is 0 and R 1 together with R 2 form an aryl ring, the aryl ring is unsubstituted; p is an integer of from 0 to 5; A j is CH or N; when p is 1, 2, 3, 4, or 5, A 2 is C(R 10 )(R π ), N(R 12 ), S, S(O), S(O) 2 , or O, and when p is 0, A 2 is C(R 10 )(R 1! )(R 12 ), N(R 10 )(R 12 ), S(R 10 ), S(O)(R 10 ), S(O) 2 (R 10 ), or O(R 10 ) where each R 10 , R 11 and R 12 is independently H or a lower alkyl group; each A 3 present is independently C(R 10 )(R n ), N(R 12 ), S, S(O), S(O) 2 , or O, where each R 10 , R 11 and R 12 is independently H or a lower alkyl group; when p is 1, 2, 3, 4, or 5, A 4 is N(R 13 ), C(R 10 )(R n ), or O, and when p is 0, A 4 is N(R 13 )(R 14 ), C(R 10 )(R U )(R 12 ), and O(R 14 ), where each R 10 , R 11 and R 12 is independently H or a lower aUcyl group, each R 13 is H or an alkyl, aryl, or acyl group, and each R 14 is H or an alkyl or aryl group; provided that no more than two heteroatoms occur consecutively in the above-depicted ring formed by A„ (A 2 ) m , (A 3 ) p , A 4 , and C=O, where each dotted line in the ring depicts a single bond when A 2 is present and a hydrogen atom when A 2 is absent; and Z and Z 1 are each independently H, F, an alkyl, cycloaUcyl, heterocycloaUcyl, aryl or heteroaryl group, where the alkyl, cycloaUcyl, heterocycloaUcyl, aryl or heteroaryl group is unsubstituted or substituted with one or more suitable substituents, -C(O)R 15 , -CO 2 R 15 , -CN, -C(O)NR 15 R 16 , -C(O)NR 15 OR 16 , -C(S)R 15 , -C(S)OR 15 , -C(S)NR ,5 R 16 , -C(=NR 15 )R 16 , -C(=NR 15 )OR 16 , -NO 2 , -SOR 16 , -SO 2 R 15 , -SO 2 NR 15 R 16 , -SO 2 (NR 15 )(OR 16 ), -SONR 15 , -SO 3 R 15 , -PO(OR 15 ) 2 , -PO(OR 15 )(OR 16 ) ; -PO(NR 15 R 16 )(OR 17 ) ; -PO(NR 15 R 16 )(NR 17 R 18 ), -C(O)NR 15 NR 16 R 17 , -C(S)NR 15 NR 16 R 17 , where R 15 , R 16 , R 17 and R 18 are each mdependently H or an alkyl, cycloalkyl, aryl, heterocycloaUcyl, acyl or thioacyl group, where the alkyl, cycloaUcyl, aryl, heterocycloalkyl, acyl or thioacyl group is unsubstituted or substituted with one or more suitable substituents, or where any two ofthe R 15 , R 16 , R 17 and R 18 , taken together with the atoms to which they are bonded, form a heterocycloalkyl group, which is unsubstituted or substituted with one or more suitable substituents, or Z and Z 1 , together with the atoms to which they are bonded, form a cycloalkyl or heterocycloaUcyl group, where Z and Z 1 are as defined above; or a prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate of said compound. 14. The compound according to claim 13, having the formula: wherein: each R z is H or a suitable substituent and n z is an integer from 1 to 4; R 7 is a moiety having the formula: wherein: R 8 and R 9 are each independently H or a lower alkyl group; p is an integer of from 1 to 5; A s CH or N; when p is 1, 2, 3, 4, or 5, A 2 is C(R 10 )(R π ), N(R 12 ), S, S(O), S(O) 2 , or O, and when p is 0, A 2 is C(R 10 )(R n )(R 12 ), N(R 10 )(R 12 ), S(R 10 ), S(O)(R 10 ), S(O) 2 (R 10 ), or O(R 10 ) where each R 10 , R 11 and R 12 is independently H or a lower alkyl group; each A 3 present is independently C(R 10 )(R π ), N(R 12 ), S, S(O), S(O) 2 , or O, where each R 10 , R 11 and R 12 is independently H or a lower alkyl group; A 4 is N(R 13 ), C(R 10 )(R n ), or O, where R 10 and R 11 are each independently H or a lower alkyl group, and R 13 is H or an alkyl, aryl or acyl group; provided that no more than two heteroatoms occur consecutively in the above-depicted ring formed by A l5 (A 2 ) m , (A 3 ) p , A 4 , and C=O; and R 3 , R 4 , R 5 , R 6 , Z and Z 1 are defined as in claim 13. 15. The compound according to claim 14, wherein each R z is independently selected from H, halo, alkoxy, unsubstituted lower alkyl, haloaUcyl, and lower alkoxyalkyl. 16. The compound according to any one of claims 12, 13 or 14, wherein: A x is CH or N; A 2 is C(R 10 )(R U ), N(R 12 ), S, S(O), S(O) 2 , or O, where each R 10 , R 11 and R 12 is independently H or a lower alkyl group; each A 3 present is independently C(R 10 )(R π ), N(R 12 ), S, S(O), S(O) 2 , or O, where each R 10 , R 11 and R 12 is independently H or a lower alkyl group; when p is 1, 2, 3, 4, or 5, A 4 is N(R 13 ), C(R I0 )(R n ), or O, and when p is 0, A 4 is N(R 13 )(R 14 ), C(R 10 )(R n )(R 12 ), and O(R 14 ), where each R 10 , R 11 and R 12 is independently H or a lower alkyl group, each R 13 is H or an alkyl, aryl, or acyl group, and each R 14 is H or an alkyl or aryl group; provided that no more than two heteroatoms occur consecutively in the above-depicted ring formed by A l5 (A 2 ) m , (A 3 ) p , A 4 , and C=O, where each dotted line in the ring depicts a single bond when A 2 is present and a hydrogen atom when A 2 is absent; and Z and Z 1 are each independently H, F, an alkyl, cycloaUcyl, heterocycloaUcyl, aryl or heteroaryl group, where the alkyl, cycloalkyl, heterocycloaUcyl, aryl or heteroaryl group is unsubstituted or substituted with one or more suitable substituents, -C(O)R 15 , -CO 2 R 15 , -CN, -C(O)NR 15 R 16 , -C(O)NR 15 OR 16 , -C(S)R 15 , -C(S)NR 15 R 16 , -NO 2 , -SOR 16 , -SO 2 R 15 , -SO 2 NR 15 R 16 , -SO 2 (NR 15 )(OR 16 ), -SONR 15 , -SO 3 R 15 , -PO(OR 15 ) 2 , -PO(OR 15 )(OR I6 ) ; -PO(NR 15 R I6 )(OR I7 ) ) -PO(NR ls R I6 )(NR I7 R 18 ), -C(O)NR 15 NR 16 R 17 , -C(S)NR 15 NR 16 R 17 , where R 15 , R 16 , R 17 and R 18 are each independently H or an alkyl, cycloaUcyl, aryl, heterocycloaUcyl, acyl or thioacyl group, where the alkyl, cycloaUcyl, aryl, heterocycloaUcyl, acyl or thioacyl group is unsubstituted or substituted with one or more suitable substituents, or where any two of the R 15 , R 16 , R 17 and R 18 , taken together with the atoms to which they are bonded, form a heterocycloalkyl group, which is unsubstituted or substituted with one or more suitable substituents, or Z and Z 1 , together with the atoms to which they are bonded, form a cycloalkyl or heterocycloaUcyl group, where Z and Z 1 are as defined above. 17. The compound according to any one of claims 12, 13 or 14, wherein said substituted alkyl, aryl, cycloaUcyl, heterocycloaUcyl or heteroaryl comprises one or more substituents independently selected from an alkyl, aryl, cycloaUcyl, heterocycloaUcyl, heteroaryl, nitro, amino, cyano, halo, hydroxyl, alkoxy, aUcylenedioxy, aryloxy, cycloaUcoxy, heterocycloalkoxy, heteroaryloxy, alkylcarbonyl, alkyloxycarbonyl, alkylcarbonyloxy, arylcarbonyl, arylcarbonyloxy, aryloxycarbonyl, cycloalkylcarbonyl, cycloalkylcarbonyloxy, cycloalkyoxycarbonyl, heteroarylcarbonyl, heteroarylcarbonyloxy, heteroaryloxycarbonyl, heterocycloalkylcarbonyl, heterocycloaUcylcarbonyloxy, heterocycloalkyoxycarbonyl, carboxyl, carbarnoyl, formyl, keto, thioketo, sulfo, aUcylamino, cycloaUcylamino, arylamino, heterocycloaUcylamino, heteroarylamino, diaUcylamino, aUcylaminocarbonyl, cycloaUcylaminocarbonyl, arylaminocarbonyl, heterocycloaUcylaminocarbonyl, heteroarylaminocarbonyl, diaUcylaminocarbonyl, aUcylaminothiocarbonyl, cycloaUcylaminothiocarbonyl, arylaminothiocarbonyl, heterocycloaUcylaminothiocarbonyl, heteroarylaminothiocarbonyl, dialkylaminothiocarbonyl, alkylsulfonyl, arylsulfonyl, alkylsulfenyl, arylsulfenyl, alkylcarbonylamino, cycloalkylcarbonylamino, arylcarbonylamino, heterocycloaUcylcarbonylamino, heteroarylcarbonylamino, alkylthiocarbonylaniino, cycloalkylthiocarbonylamino, arylthiocarbonylamino, heterocycloaUcylthiocarbonylamino, heteroarylthiocarbonylamino, aUcylsulfonyloxy, arylsulfonyloxy, alkylsulfonylamino, arylsulfonylamino, mercapto, aUcylthio, arylthio and heteroarylthio group, where any ofthe alkyl, alkylene, aryl, cycloaUcyl, heterocycloaUcyl, heteroaryl moieties present in the above substituents may be further substituted with one or more suitable substituents. 18. The compound according to any one of claims 12, 13 or 14, wherein said substituted alkyl, alkylene, aryl, cycloaUcyl, heterocycloaUcyl, heteroaryl moieties may be further substituted with one or more suitable substituents selected from nitro, amino, cyano, halo, haloalkyl, haloaryl, hydroxyl, keto, hydroxamino, aUcylamino, m-aUcylamino, mercapto, and unsubstituted alkyl, aryl, cycloaUcyl, heterocycloaUcyl, heteroaryl, alkoxy, aryloxy, aUcylthio or arylthio groups and wherein said aryl or heteroaryl moieties may be substituted with aUcylenedioxy. 19. An antipicornaviral compound having the formula: wherein: R a ' is an alkyl, aryl, cycloalkyl, heterocycloaUcyl or heteroaryl, unsubstituted or substituted with one or more suitable substituents,; R 5 is H or an alkyl group, unsubstituted or substituted with one or more suitable substituents,; each R 6 is independently H or a lower alkyl group, unsubstituted or substituted with one or more suitable substituents,; R 7 is a moiety having the formula: wherein: R 8 and R 9 are each independently H or a lower alkyl group; m is 0 or 1 ; p is an integer of from 0 to 5; when p is 1, 2, 3, 4, or 5, A 2 is C(R 10 )(R π ), N(R 12 ), S, S(O), S(O) 2 , or O, and when p is 0, A 2 is C(R 10 )(R n )(R 12 ), N(R 10 )(R 12 ), S(R 10 ), S(O)(R 10 ), S(O) 2 (R 10 ), or O(R 10 ), where each R 10 , R 11 and R 12 is independently H or a lower alkyl group; each A 3 present is independently C(R 10 )(R π ), N(R 12 ), S, S(O), S(O) 2 , or O, where each R 10 , R 11 and R 12 is each independently H or a lower alkyl group; when p is 1, 2, 3, 4, or 5, A 4 is N(R 13 ), C(R 10 )(R n ), or O, and when p is 0, A 4 is N(R 13 )(R 14 ), C(R 10 )(R n )(R 12 ), and O(R 14 ), where each R 10 , R" and R 12 is independently H or a lower alkyl group, each R 13 is H or an alkyl, aryl, or acyl group, and each R 14 is H or an alkyl or aryl group; provided that no more than two heteroatoms occur consecutively in the above-depicted ring formed by A l5 (A 2 ) m , (A 3 ) p , A 4 , and C=O, where each dotted line in the ring depicts a single bond when A 2 is present and a hydrogen atom when A 2 is absent; and Z and Z 1 are each independently H, F, an alkyl, cycloaUcyl, heterocycloaUcyl, aryl or heteroaryl group, where the alkyl, cycloaUcyl, heterocycloalkyl, aryl or heteroaryl group is unsubstituted or substituted with one or more suitable substituents, -C(O)R 15 , -CO 2 R 15 , -CN, -C(O)NR 15 R 16 , -C(O)NR 15 OR 16 , -C(S)R 15 , -C(S)OR 15 , -C(S)NR 15 R 16 , -C(=NR 1S )R 16 , -C(=NR 15 )OR 16 , -NO 2 , -SOR 16 , -SO 2 R 15 , -SO 2 NR 15 R 16 , -SO 2 (NR 15 )(OR 16 ), -SONR 15 , -SO 3 R 15 , -PO(OR 15 ) 2 , -PO(OR 15 )(OR 16 ) > -PO(NR 15 R 16 )(OR 17 ) ; -PO(NR 15 R 16 )(NR 17 R 18 ), -C(O)NR 15 NR 16 R 17 , -C(S)NR 15 NR 16 R 17 , where R 15 , R 16 , R 17 and R 18 are each independently H or an alkyl, cycloaUcyl, aryl, heterocycloaUcyl, acyl or thioacyl group, where the alkyl, cycloaUcyl, aryl, heterocycloalkyl, acyl or thioacyl group is unsubstituted or substituted with one or more suitable substituents, or where any two ofthe R 15 , R 16 , R 17 and R 18 , taken together with the atoms to which they are bonded, form a heterocycloalkyl group, which is unsubstituted or substituted with one or more suitable substituents, or Z and Z 1 , together with the atoms to which they are bonded, form a cycloalkyl or heterocycloaUcyl group, where Z and Z 1 are as defined above; or a prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate of said compound. 20. The compound according to claim 19, wherein: A^s CH orN; A 2 is C(R 10 )(R U ), N(R 12 ), S, S(O), S(O) 2 , or O, where each R 10 , R 11 and R 12 is independently H or a lower alkyl group; each A 3 present is independently C(R 10 )(R U ), N(R 12 ), S, S(O), S(O) 2 , or O, where each R 10 , R 11 and R 12 is independently H or a lower alkyl group; when p is 1, 2, 3, 4, or 5, A 4 is N(R 13 ), C(R 10 )(R π ), or O, and when p is 0, A 4 is N(R 13 )(R 14 ), C(R 10 )(R U )(R 12 ), and O(R 14 ), where each R 10 , R 11 and R 12 is independently H or a lower alkyl group, each R 13 is H or an alkyl, aryl, or acyl group, and each R 14 is H or an alkyl or aryl group; provided that no more than two heteroatoms occur consecutively in the above-depicted ring formed by A 1? (A 2 ) m , (A 3 ) p , A 4 , and C=O, where each dotted line in the ring depicts a single bond when A 2 is present and a hydrogen atom when A 2 is absent; and Z and Z 1 are each independently H, F, an alkyl, cycloaUcyl, heterocycloaUcyl, aryl or heteroaryl group, where the alkyl, cycloaUcyl, heterocycloaUcyl, aryl or heteroaryl group is unsubstituted or substituted with one or more suitable substituents, -C(O)R 15 , -CO 2 R 15 , -CN, -C(O)NR 15 R 16 , -C(O)NR 15 OR 16 , -C(S)R 15 , -C(S)NR 15 R 16 , -NO 2 , -SOR 16 , -SO 2 R 15 , -SO 2 NR 15 R 16 , -SO 2 (NR 13 )(OR 16 ), -SONR 15 , -SO 3 R 15 , -PO(OR 15 ) 2 , -POCOR^COR 16 ) , -PO(NR 15 R 16 )(OR 17 ) , -PO(NR 15 R 16 )(NR ,7 R 18 ), -C(O)NR 15 NR 16 R 17 , -C(S)NR ,5 NR 16 R 17 , where R 15 , R 16 , R 17 and R 18 are each independently H or an alkyl, cycloalkyl, aryl, heterocycloaUcyl, acyl or thioacyl group, where the alkyl, cycloaUcyl, aryl, heterocycloaUcyl, acyl or thioacyl group is unsubstituted or substituted with one or more suitable substituents, or where any two of the R 15 , R 16 , R 17 and R 18 , taken together with the atoms to wliich they are bonded, form a heterocycloalkyl group, which is unsubstituted or substituted with one or more suitable substituents, or Z and Z 1 , together with the atoms to which they are bonded, form a cycloaUcyl or heterocycloalkyl group, where Z and Z 1 are as defined above. 21. The compound according to any one of claims 8, 9, 12, 13, 14, 19 or 20, wherein R 5 is H or a lower alkyl, arylalkyl, heteroarylalkyl or cycloaUcylaUcyl group, a straight-chain saturated hydrocarbon moiety or an unsaturated hydrocarbon moiety, where said lower alkyl, arylalkyl, heteroarylalkyl or cycloaUcylaUcyl group is unsubstituted or substituted with one or more suitable substituents. 22. The compound according to claim 21, wherein R 5 is H or a methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, 2-propen-l-yl, 2-propen-2-yl, 2-propyn-l-yl, 3 -methyl-3 -buten- 1-yl, -methylcyclohexyl, -methylthienyl or benzyl group, unsubstituted or substituted with one or more suitable substituents. 23. The compound according to claim 16, wherein R s is H or a methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, 2-propen-l-yl, 2-propen-2-yl, 2-propyn-l-yl, 3 -methyl-3 -buten- 1-yl, -methylcyclohexyl, -methylthienyl or benzyl group, unsubstituted or substituted with one or more suitable substituents. 24. The compound according to claim 21, wherein said substituted methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, 2-propen-l-yl, 2-propen-2-yl, 2-propyn-l-yl, 3 -methyl-3 -buten- 1-yl, -methylcyclohexyl group is substituted by one or more substituents independently selected from halo, alkoxy, aryloxy, aUcylthio and arylthio. 25. The compound according to claim 21 , wherein the thienyl moiety of the -methylthienyl group is substituted by one or more substituents independently selected from lower alkyl, lower alkoxy, hydroxy, amino, aUcylamino, diaUcylamino and halo. 26. The compound according to claim 21 , wherein the phenyl moiety of the substituted benzyl is substituted by one or more substituents independently selected from lower alkyl, lower alkoxy, aUcylenedioxy, hydroxy, amino, aUcylamino, dialkylamino and halo. 27. The compound according to any one of claims 8, 9, 12, 13, 14, 19 or 20, wherein R 5 is H, ethyl, 2-propyn-l-yl, methylcyclohexyl, or substituted or unsubstituted benzyl, where the phenyl moiety ofthe substituted benzyl comprises one or more substituents independently selected from lower alkyl, lower alkoxy and halo. 28. The compound according to claim 16, wherein R 5 is H, ethyl, 2-propyn-l-yl, methylcyclohexyl, or substituted or unsubstituted benzyl, where the phenyl moiety of the substituted benzyl comprises one or more substituents independently selected from lower alkyl, lower alkoxy and halo. 29. The compound, prodrug, pharmaceutically acceptable salt, pharmaceuticaly active metabolite, or pharmaceutically acceptable salt according to any one of claims 8, 9, 12, 13, 14, 19 or 20, where m is 0 and p is 0 or m is 1 and p is 1 or 2. 30. The compound according to any one of claims 8, 9, 12, 13, 14, 19 or 20„ wherein R 7 is selected from -CH 2 CH 2 C(O)NH 2 ; -CH 2 CH 2 C(O)NH-alkyl; -CH 2 NHC(O)CH 3 ; and , where n is 1 or 2. 31. The compound according to claim 16, wherein R 7 is selected from -CH 2 CH 2 C(O)NH 2 ; -CH 2 CH 2 C(O)NH-alkyl; -CH 2 NHC(O)CH 3 ; and , where n is 1 or 2. 32. The compound according to any one of claims 8, 9, 12, 13, 14, 19 or 20, wherein R 7 is 33. The compound, prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate according to any one of claims 8, 12, 13 or 19, wherein Z and Z 1 are each independently selected from H, alkyl, where the alkyl is unsubstituted or substituted with one or more suitable substituents, and -CO 2 R 15 or taken together with the atom to which they are attached, form a heterocycloaUcyl group, wliich is optionally substituted with one or more suitable substituents. 34. The compound, prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate according to claim 9, wherein Z and Z 1 are each independently selected from H, lower alkyl which is unsubstituted or substituted with one or more suitable substituents, -CO 2 H, -CO 2 -alkyl and -CO 2 -cycloalkyl, or taken together with the atom to which they are attached form a heterocycloaUcyl group , wliich is optionally substituted with one or more of keto or thioketo. 35. The compound, prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate according to claim 16, wherein Z and Z 1 are each independently selected from H, lower alkyl which is unsubstituted or substituted with one or more suitable substituents, -CO 2 H, -CO 2 -alkyl and -CO 2 -cycloalkyl, or taken together with the atom to which they are attached form a heterocycloalkyl group , which is optionally substituted with one or more of keto or thioketo. 36. The compound, prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate according to claim 20, wherein Z and Z 1 are each independently selected from H, lower alkyl which is unsubstituted or substituted with one or more suitable substituents, -CO 2 H, -CO 2 -alkyl and -CO 2 -cycloalkyl, or taken together with the atom to which they are attached form a heterocycloalkyl group , which is optionally substituted with one or more of keto or thioketo. 37. The compound, prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate according to any one of claims 8, 12, 13 or 19, wherein Z and Z 1 are not both H. 38. The compound according to claim 9, wherein Z 1 is H and Z is -CO 2 CH 2 CH 3 , -CO 2 (CH(CH 3 ) 2 ), -CO 2 (C(CH 3 ) 3 ), -CO 2 CH 2 (C(CH 3 ) 3 ), -CO 2 (cyclo-C 3 H 9 ) orZ 1 and Z taken together with the atom to which they are attached form 39. The compound according to claim 16, wherein 7) is H and Z is -CO 2 CH 2 CH 3 , -CO 2 (CH(CH 3 ) 2 ), -CO 2 (C(CH 3 ) 3 ), -CO 2 CH 2 (C(CH 3 ) 3 ), -CO 2 (cyclo-C 5 H 9 )or Z 1 and Z taken together with the atom to which they are attached form 40. The compound, prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate according to any one of claims 1, 8, 12, 13 or 19, wherein Z 1 is H or a lower alkyl and Z is -CO 2 H, -CO 2 -alkyl, -CO 2 -aUcylaryl, -CO 2 -alkylheteroaryl, -CO 2 -cycloalkyl group, where the lower alkyl, -alkyl, -cycloalkyl, -alkylaryl, -aUcylheteroaryl moieties thereof are unsubstituted or substituted with one or more suitable substituents, or Z 1 and Z taken together with the atom to which they are attached form a heterocycloalkyl group, which is optionally substituted. 41. The compound, prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate according one of claims 8, 12, 13, 19 or 20, wherein Z is selected from ethoxycarbonyl, t-butoxycarbonyl, isopropoxycarbonyl, (2,2-dimethylpropyl)-oxycarbonyl, benzyloxycarbonyl, pyridylmethyleneoxycarbonyl, cyclobutyloxycarbonyl, cyclopentyloxycarbonyl, cyclohexyloxycarbonyl and cycloheptyloxycarbonyl, where the ethoxy, t-butoxy, isopropoxy, (2,2-dimethylpropyl)-oxy, benzyl, pyridylmethylene, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl moieties thereof are unsubstituted or substituted with one or more suitable substituents, or Z 1 and Z taken together with the atom to which they are attached form 42. The compound, prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate according claim 41, wherein Z is selected from ethoxycarbonyl, t-butoxycarbonyl, isopropoxycarbonyl, (2,2- dimethylpropyl)-oxycarbonyl, benzyloxycarbonyl, pyridylmethyleneoxycarbonyl, cyclobutyloxycarbonyl, cyclopentyloxycarbonyl, cyclohexyloxycarbonyl and cycloheptyloxycarbonyl, or Z 1 and Z taken together with the atom to which they are attached form 43. The compound according to claim 10, having the formula: wherein R a ' is an alkyl, cycloalkyl, aryl or heteroaryl group, where said alkyl, cycloalkyl, aryl, and heteroaryl group is unsubstituted or substituted with one or more suitable substituents, and each R 4 , R 5 , R 6 , R 7 , Z and Z 1 are defined as in claim 10. 44. The compound according to claim 11, having the formula:: wherein R a' is an alkyl, cycloalkyl, aryl or heteroaryl group, where said alkyl, cycloaUcyl, aryl, and heteroaryl group is unsubstituted or substituted with one or more suitable substituents, and each R 4 , R 5 , R 6 , R 7 , Z and Z 1 are defined as in claim 11. 45. The compound according to claim 12, having the formula: wherein R 1 is an alkyl, cycloaUcyl, heterocycloaUcyl, aryl or heteroaryl group, where the alkyl, cycloaUcyl, heterocycloalkyl, aryl, and heteroaryl group is unsubstituted or substituted with one or more suitable substituents, and each R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , Z and Z 1 are defined as in claim 12. 46. The compound according to claim 13, having the formula: wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , Z and Z 1 are defined as in claim 13. 47. The compound according to claim 14, having the formula: wherein R z , R 3 , R 4 , R 5 , R 6 , R 7 , Z and Z 1 are defmed as in claim 14. 48. The compound according to claims 12 or 13, wherein R 1 is selected from H and a lower alkyl, phenyl, naphthyl, pyridyl, quinoyl, isoquinoyl or isoxazoyl group, where the lower alkyl, phenyl, naphthyl, pyridyl, quinoyl, isoquinoyl or isoxazoyl group is unsubstituted or substituted with one or more substituents selected from alkyl, hydroxy, halo, haloaUcyl, alkoxy, haloaUcoxy and aUcylenedioxy moiety. 49. An antipicornaviral compound having the formula: wherein: R a is (C r C 4 )aUcylcarbonyl-(C r C 4 )aUcyl, (C 3 -C 8 )cycloaUcylcarbonyl-(C 1 -C 4 )aUcyl, arylcarbonyl-(C r C 4 )alkyl, heteroarylcarbonyl-^ j -C aUcyl, (C j -C^allcylcarbonylamino^ -C^alkyl, (C 3 -C 8 ) cycloalkylcarbonylamino^C j -C^alkyl, heterocycloalkylcarbonylamino-(C 1 -C 4 )alkyl, arylcarbonylamino-^-Q alkyl, heteroarylcarbonylamino-(C 1 -C 4 )aUcyl, (C r C 4 aUcylaminocarbonyl-(Cι-C 4 )aUcyl, (C 3 -C 8 )cycloalkylaminocarbonyl-(C 1 -C 4 )aUcyl, heterocycloalkylaminocarbonyl^C j -C alkyl, arylaminocarbonyl-(C 1 -C 4 )aUcyl, heteroarylaminocarbonyl-(C ]1 -C 4 )aUcyl, wherein each (C r C 4 )aUcyl, (C 3 -C 8 )cycloalkyl, heterocycloaUcyl, aryl and heteroaryl moiety thereof is unsubstituted or substituted with one or more suitable substituents; R b and R d are each independently H or C,-C 4 alkyl; R c is selected from -CH 2 CH 2 C(O)NH 2 ; -CH 2 CH 2 C(O)NH-alkyl; -CH 2 NHC(O)CH 3 ; and , where n is 1 or 2; and Z 1 is H or C r C 4 aUcyl and Z is -CO 2 -aUcyl, -CO 2 -cycloaUcyl, -CO 2 -aUcylaryl or -CO 2 -alkylheterocycloaryl, or Z 1 and Z taken together with the atom to which they are attached form provided that R c is , where n is 1 or 2 when R is an indolylcarbonylamino-(C 1 -C 4 )aUcyl group where the indolyl moiety thereof is substituted with one or more suitable substituents or R a is is not an amino-substituted (C 1 -C 4 )alkylcarbonylamino-(C 1 -C 4 )alkyl or R a is is not an amino-substituted (C 1 -C 4 )aUcylcarbonyl-(C 1 -C 4 )aUcyl; and R c is selected from -CH 2 CH 2 C(O)NH 2 ; -CH 2 CH 2 C(O)NH-alkyl; -CH 2 NHC(O)CH 3 ; and where n is 1 or 2, when R a is an indolylcarbonylamino-(C 1 -C 4 )alkyl group where the indolyl moiety thereof is unsubstituted or R a is a (C r C 4 ) alkylaminocarbonyl^Cj-C^alkyl, (C 3 -C 8 )cycloaUcylaminocarbonyl-(C 1 -C 4 )alkyl, heterocycloalkylaminocarbonyl-(C 1 -C 4 )aUcyl, arylaminocarbonyl-(C 1 -C 4 )aUcyl, heteroarylaminocarbonyl-(C 1 -C 4 )aUcyl, or heteroarylcarbonylamino-(C 1 -C 4 )aUcyl group, wherein each (C r C 4 )alkyl, (C 3 -C 8 )cycloaUcyl, heterocycloalkyl, aryl and heteroaryl moiety thereof is unsubstituted or substituted with one or more suitable substituents. 50. The compound according to claim 49, wherein: R a is (C r C 4 )alkyιcarbonyl-(C r C 4 )alkyl, (C 5 -C 6 )cycloaUcylcarbonyl-(C r C 4 )aUcyl, arylcarbonyl-(C 1 -C 4 )aUcyl, heteroarylcarbonyl-^j-C^aUcyl, (Cj-C alkylcarbonylamino^Cj-C^alkyl, C 3 -C 8 cycloaUcylcarbonylamino-(C 1 ~C 4 )alkyl, heterocycloalkylcarbonylamino^ -C alkyl, arylcarbonylamino^ -C^alkyl, heteroarylcarbonylamino-^j-C^aUcyl, (C r C 4 aUcylarninocarbonyl-^j-C alkyl, (C 5 -C 6 )cycloalkylaminocarbonyl-(C,-C 4 )aUcyl, heterocycloalkylaminocarbonyl- (C r C 4 )aUcyl, wherein each (C j -C^alkyl, (C 3 -C 8 )cycloaUcyl, heterocycloaUcyl, aryl and heteroaryl moiety thereof is unsubstituted or substituted with one or more suitable substituents; R c is -CH 2 CH 2 C(O)NH 2 where n is 1 ; and Z 1 is H and Z is -CO 2 CH 2 CH 3 , -CO 2 (CH(CH 3 ) 2 ), -CO 2 (C(CH 3 ) 3 ), -CO 2 CH 2 (C(CH 3 ) 3 ), -CO 2 (cyclo-C 5 H 9 ) or Z 1 and Z taken together with the atom to which they are attached form R c is , where n is 1 , when R a is an indolylcarbonylamino-(C 1 -C 4 )alkyl group where the indolyl moiety thereof is substituted with one or two substituents independently selected from halo, Cj- alkoxy, unsubstituted C r C 4 alkyl and C r C 4 haloaUcyl, C r C 4 haloaUcoxy, methylenedioxy, aryl, heterocycloaUcyl, and heteroaryl where the aryl, heterocycloaUcyl and heteroaryl is unsubstituted or substituted by one ore more substituents independently selected from halo, C r C 4 alkyl, C r C 4 haloaUcyl, C r C 4 alkoxy, Cj-C 4 haloalkoxy and methylenedioxy; and R c is selected from -CH 2 CH 2 C(O)NH 2 ; -CH 2 CH 2 C(O)NH-alkyl; -CH 2 NHC(O)CH 3 ; and , where n is 1 , when R a is arylcarbonyl-(C , -C 4 )alkyl, heteroarylcarbonyl-(C, -C 4 )aUcyl, (Cj-C^alkylcarbonylamino^Ci-C alkyl, C 3 -C 8 cycloaUcylcarbonylamino-(C 1 -C 4 )aUcyl, heterocycloaUcylcarbonylamino-^j-C^aUcyl, arylcarbonylamino-(C r C 4 )alkyl, heteroarylcarbonylamino-(C,-C 4 )aUcyl, (Ci-C 4 alkylaminocarbonyl-(Ci-C 4 )alkyl, (C 3 -C 8 )cycloaUcylaminocarbonyl-(C 1 -C 4 )aUcyl, heterocycloalkylaminocarbonyl- (C r C 4 )aUcyl, arylaminocarbonyl-(C 1 -C 4 )aUcyl, heteroarylaminocarbonyl-(C 1 -C 4 )alkyl, wherein each (C 1 -C 4 )aUcyl, (C 3 -C 8 )cycloaUcyl, heterocycloaUcyl, aryl and heteroaryl moiety thereof unsubstituted or substituted with one or more suitable substituents. 51. The compound according to claim 49, wherein: R a is (C 1 -C 4 )alkylcarbonyl-(C 1 -C 4 )aUcyl, phenylcarbonyl-(C 1 -C 4 )aUcyl, naphthylcarbonyl-(C,-C 4 )aUcyl, pyrrolylcarbonyl-(Ci-C 4 )aUcyl, indolylcarbonyl-(C 1 -C 4 )aUcyl, (C j -C^alkylcarbonylamino-^-C^alkyl, pyrrolylcarbonylamino-(C,-C 4 )alkyl, indolylcarbonylamino-(C 1 -C 4 )aUcyl, phenylcarbonylamino-(C 1 -C 4 )aUcyl, naphthylcarbonylamino-(C r C 4 )aUcyl, (C 1 -C 4 )aUcylaminocarbonyl-(C 1 -C 4 )aUcyl, phenylaminocarbonyl-^ C^aUcyl, naphthylaminocarbonyl-(C 1 -C 4 )aUcyl, wherein each (C r C 4 )aUcyl, phenyl, naphthyl, pyrrolyl, and indolyl moiety thereof is unsubstituted or substituted with one or more substituents independently selected from halo, - alkyl, Cj- haloaUcyl, C C 4 alkoxy, C r C 4 haloaUcoxy, methylenedioxy, aryl, heterocycloaUcyl, and heteroaryl, where the aryl, heterocycloalkyl or heteroaryl is unsubstituted or substituted by one ore more substituents independently selected from halo, C r C 4 alkyl, C r C 4 haloaUcyl, - alkoxy, Cj- haloaUcoxy and methylenedioxy; R b and R d are each H; R° is -CH 2 CH 2 C(O)NH 2 or ; and Z 1 is H and Z is -CO 2 CH 2 CH 3 or Z 1 and Z taken together with the atom to which they are attached form provided that R c is indolylcarbonylamino-(C 1 -C 4 )alkyl group where the indolyl moiety thereof is substituted with one or two substituents independently selected from halo, C r C 4 alkoxy, unsubstituted C r C 4 alkyl and C r C 4 haloaUcyl; and and R c is -CH 2 CH 2 C(O)NH 2 or , when R a is (C 1 -C 4 )aUcylcarbonyl-(C 1 -C 4 )aUcyl, naphthylcarbonyl-(C r C 4 )aUcyl, pyrrolylcarbonyl-(C 1 -C 4 )aUcyl, indolylcarbonyl-(C r C 4 )aUcyl, (C 1 -C 4 )aUcylcarbonylamino-(C 1 -C 4 )aUcyl, pyrrolylcarbonylamino-(C 1 -C 4 )aUcyl, indolylcarbonylamino-^j-C^aUcyl, phenylcarbonylamino-(Ci-C 4 )aUcyl, naphthylcarbonylamino-(C 1 -C 4 )aUcyl, (C 1 -C 4 )alkylaminocarbonyl-(C 1 -C 4 )aUcyl, phenylaminocarbonyl-(C r C 4 )aUcyl, naphthylaminocarbonyl-(C 1 -C 4 )aUcyl, wherein each (C r C 4 )aUcyl, phenyl, naphthyl and pyrrolyl moiety thereof is group is unsubstituted or substituted with one or more substituents independently selected from halo, C r C 4 alkyl, C r C 4 haloaUcyl, Cj-C 4 alkoxy, C r C 4 haloaUcoxy, methylenedioxy, aryl, heterocycloaUcyl, and heteroaryl, where the aryl, heterocycloalkyl and heteroaryl is unsubstituted or substituted by one ore more substituents independently selected from halo, Cj-C 4 alkyl, Cj-C 4 haloaUcyl, C r C 4 alkoxy, C r C 4 haloaUcoxy and methylenedioxy; and said indolyl moiety is unsubstituted. 52. The compound according to claim 49 having the formula: wherein: R a' is a (C r C 4 )aUcyl, (C 3 -C 8 )cycloaUcyl, aryl or heteroaryl group, wherein the (C r C 4 )aUcyl, (C 3 -C 8 )cycloalkyl, aryl and heteroaryl group is unsubstituted or substituted with one or more substituents independently selected from aryl, (C 3 -C 8 )cycloalkyl, heterocycloalkyl, heteroaryl, halo, hydroxyl, ( -C alkoxy, aUcylenedioxy, aryloxy, (C 3 -C 8 )cycloalkoxy, heteroaryloxy, and carboxyl where the (C 1 -C 4 )alkyl, aryl, (C 3 -C 8 )cycloaUcyl, heterocycloaUcyl, heteroaryl moieties thereof are optionally substituted by one or more of (C 1 -C 4 )alkyl, ( -C^haloalkyl or aryl, where the aryl is unsubstituted or substituted with one or more substituents independently selected from alkyl, haloalkyl, alkylenedioxy, nitro, amino, hydroxamino, alkylamino, dialkylamino, halo, hydroxyl, alkoxy, haloalkoxy, aryloxy, mercapto, aUcylthio or arylthio; R b and R d are each independently H or C r C 4 alkyl; n is 1, 2 or 3; R x is H and R y is H, C C 4 alkyl, C r C 4 haloaUcyl or an arylalkyl, heteroarylalkyl, cycloaUcylaUcyl group or a straight-chain saturated hydrocarbon moiety or an unsaturated hydrocarbon moiety, where the arylalkyl, heteroarylalkyl, cycloaUcylaUcyl group is unsubstituted or substituted with one or more suitable substituents; R c is , where n is 1 or 2; and Z 1 is H or C r C 4 alkyl and Z is -CO 2 -alkyl, -CO 2 -cycloaUcyl, -CO 2 -aUcylaryl or -CO 2 -aUcylheterocycloaryl, or Z 1 and Z taken together with the atom to which they are attached form 53. The compound according to claim 52, wherein: R a ' is a (Cι-C 4 )aUcyl, pyrrolyl, indolyl, phenyl or naphthyl group, where the group is unsubstituted or substituted with one or more substituents independently selected from halo, C r C 4 alkoxy or C r C 4 haloaUcoxy and the pyrrolyl, indolyl, phenyl or naphthyl group is unsubstituted or substituted with one or more substituents independently selected from halo, C r C 4 alkyl, C r C 4 haloaUcyl, C j -C 4 aUcoxy, C r C 4 haloaUcoxy, methylenedioxy, aryl, heterocycloaUcyl and heteroaryl, where the aryl, heterocycloalkyl and heteroaryl is unsubstituted or substituted by one or more substituents independently selected from halo, C r C 4 alkyl, C r C 4 haloaUcyl, -Q, aUcoxy, C x -C 4 haloalkoxy and methylenedioxy R b and R d are each H; n is 1 or 2; R x is H and R y is substituted or unsubstituted methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, 2-propen-l-yl, 2-propen-2-yl, 2-propyn-l-yl, 3-methyl-3-buten-l-yl, -methylcyclohexyl, -methylthienyl or benzyl, where the substituted methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, 2-propen-l-yl, 2-propen-2-yl, 2-propyn-l-yl, 3 -methyl-3 -buten- 1-yl, and -methylcyclohexyl is substituted by one or more substituents independently selected from halo, aUcoxy, aryloxy, aUcylthio and arylthio; the subsituted thienyl is substituted by one or more substituents independently selected from lower alkyl, lower aUcoxy, hydroxy, amino, aUcylamino, dialkylamino and halo; and the phenyl moiety ofthe substituted benzyl is substituted by one or more substituents independently selected from lower alkyl, lower aUcoxy, aUcylenedioxy, hydroxy, amino, aUcylamino, diaUcylamino and halo; R c is where n is i; and Z 1 is H and Z is -CO 2 CH 2 CH 3 , -CO 2 (CH(CH 3 ) 2 ), -CO 2 (C(CH 3 ) 3 ), -CO 2 CH 2 (C(CH 3 ) 3 ), -CO 2 (cyclo-C 5 H 9 ) or Z 1 and Z taken together with the atom to which they are attached form 54. The compound according to claim 52, wherein: R a' is an unsubstituted (C r C 4 )aUcyl, or a pyrrolyl, indolyl, phenyl or naphthyl group, where the pyrrolyl, indolyl, phenyl or naphthyl group is unsubstituted or substituted by one or more substituents independently selected from halo, Cj-C 4 alkyl, C r C 4 haloaUcyl or a phenyl, naphthyl, isoxazolyl, pyridyl, quinoyl or isoquinoyl group, where the phenyl, naphthyl, isoxazolyl, pyridyl, quinoyl or isoquinoyl group is unsubstituted or substituted with one or more substituents independently selected from halo, C r C 4 alkyl, C r C 4 haloaUcyl, C r C 4 aUcoxy, C r C 4 haloaUcoxy and methylenedioxy; R and R d are each H; n is 2; R x is H and R y is ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, 2-propen-l-yl, 2-propen-2-yl, 2-propyn-l-yl, 3-methyl-3-buten-l-yl, -methylcyclohexyl, benzyl or substituted benzyl, wherein the phenyl moiety ofthe substituted benzyl comprises one or more substituents independently selected from C r C 4 alkyl, C r C 4 aUcoxy and halo; Z 1 is H and Z is -CO 2 CH 2 CH 3 or Z 1 and Z taken together with the atom to which they are attached form 55. The compound according to claim 49, having the formula: wherein: R a' is a ( -C alkyl, phenyl, naphthyl, pyrrolyl or indolyl group, where the (Cι-C 4 )alkyl group is unsubstituted or substituted with one or more substituents independently selected from halo, - alkoxy or -Q, haloalkoxy and the phenyl, naphthyl, pyrrolyl or indolyl group is unsubstituted or substituted with one or more substituents independently selected from halo, C r C 4 alkyl, C r C 4 haloalkyl, C r C 4 aUcoxy, C r C 4 haloalkoxy, methylenedioxy, aryl, heterocycloaUcyl, and heteroaryl, where the aryl, heterocycloaUcyl or heteroaryl is unsubstituted or substituted by one ore more substituents independently selected from halo, C r C 4 alkyl, Cj-C 4 haloaUcyl, C r C 4 alkoxy, C r C 4 haloalkoxy and methylenedioxy; n is 1, 2 or 3, R x is H and R y is H, C r C 4 alkyl, C r C 4 haloaUcyl or an arylalkyl, heteroarylalkyl, cycloaUcylaUcyl group or a straight-chain saturated hydrocarbon moiety or an unsaturated hydrocarbon moiety, where the arylalkyl, heteroarylalkyl, cycloaUcylaUcyl group is unsubstituted or substituted with one or more suitable substituents. R b and R d are each independently H or C r C 4 alkyl; R c is , where n is 1 or 2; and Z 1 is H or C r C 4 aUcyl and Z is -CO 2 -alkyl, -CO 2 -cycloaUcyl, -CO 2 -alkylaryl or -CO 2 -aUcylheterocycloaryl, or 7) and Z taken together with the atom to which they are attached form 56. The compound according to claim 55, wherein: R a ' is a pyrrolyl or indolyl group, where the pyrrolyl or indolyl group is unsubstituted or substituted by one or more substituents independently selected from halo, C r C 4 alkyl, C r C 4 haloalkyl or a phenyl, naphthyl, isoxazolyl, pyridyl, quinoyl or isoquinoyl group, where the phenyl, naphthyl, isoxazolyl, pyridyl, quinoyl or isoquinoyl group is unsubstituted or substituted with one or more substituents independently selected from: halo, C r C 4 alkyl, C r C 4 haloaUcyl, C r C 4 aUcoxy, -Q, haloaUcoxy and methylenedioxy; R b and R d are each H; n is 1 or 2; R x is H and R y is substituted or unsubstituted methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, 2-propen-l-yl, 2-propen-2-yl, 2-propyn-l-yl, 3 -methyl-3 -buten- 1-yl, -methylcyclohexyl, -methylthienyl or benzyl, where the substituted methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, 2-propen-l-yl, 2-propen-2-yl, 2-propyn-l-yl, 3 -methyl-3 -buten- 1-yl, and -methylcyclohexyl is substituted by one or more substituents independently selected from halo, alkoxy, aryloxy, aUcylthio and arylthio; the subsituted thienyl is substituted by one or more substituents independently selected from lower alkyl, lower aUcoxy, hydroxy, amino, aUcylamino, dialkylamino and halo; and the phenyl moiety ofthe substituted benzyl is substituted by one or more substituents independently selected from lower alkyl, lower aUcoxy, aUcylenedioxy, hydroxy, amino, aUcylamino, diaUcylamino and halo; R c is where n is i; and Z 1 is H and Z is -CO 2 CH 2 CH 3 , -CO 2 (CH(CH 3 ) 2 ), -CO 2 (C(CH 3 ) 3 ), -CO 2 CH 2 (C(CH 3 ) 3 ), -CO 2 (cyclo-C 5 H 9 ) or Z 1 and Z taken together with the atom to which they are attached form 57. The compound according to claim 55, wherein: R a ' is a pyrrolyl group that is unsubstituted or substituted by phenyl, α-naphthyl, β-naphthyl, 2-chlorophenyl, 2- ,α,α-trifluoromethylphenyl, 3-chloro-6-methoxyphenyl, 2,3-dichlorophenyl, 4-isoquinoyl, 3-iso-propylphenyl, 2,5-dimethoxyphenyl, 2-methoxyphenyl, 2-methylphenyl (o-tolyl), 2-bromophenyl, 3-pyridyl, 4-pyridyl, 3-methyl-isoxazol-5-yl, 3,3,3-trifluoroprop-l-yl, or 2,3-benzo[d]dioxolyl; R and R d are each H; n is 1; R x is H and R y is ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, 2-propen-l-yl, 2-propen-2-yl, 2-propyn-l-yl, 3-methyl-3-buten-l-yl, -methylcyclohexyl, benzyl or substituted benzyl, wherein the phenyl moiety ofthe substituted benzyl comprises one or more substituents independently selected from C r C 4 alkyl, Cj- aUcoxy and halo; Z 1 is H and Z is -CO 2 CH 2 CH 3 or Z 1 and Z taken together with the atom to which they are attached form 58. The compound according to claim 49, having the formula: wherein: R a? is a (C j - alkyl, (C 3 -C 8 )cycloaUcyl, heterocycloaUcyl, aryl or heteroaryl group, wherein the (C j -C^alkyl, (C 3 -C 8 )cycloalkyl, heterocycloaUcyl, aryl and heteroaryl group is unsubstituted or substituted with one or more suitable substituents; n is 1, 2 or 3; R x is H and R y is H, C r C 4 alkyl, C r C 4 haloalkyl or an arylaUcyl, heteroarylalkyl, cycloaUcylaUcyl group or a straight-chain saturated hydrocarbon moiety or an unsaturated hydrocarbon moiety, where the arylaUcyl, heteroarylalkyl, cycloaUcylaUcyl group is unsubstituted or substituted with one or more suitable substituents; R c is selected from -CH 2 CH 2 C(O)NH 2 ; -CH 2 CH 2 C(O)NH-alkyl; -CH 2 NHC(O)CH 3 ; and , where n is 1 or 2; and Z 1 is H or C r C 4 alkyl and Z is -CO 2 -aUcyl, -CO 2 -cycloaUcyl, -CO 2 -alkylaryl or -CO 2 -aUcylheterocycloaryl, or Z 1 and Z taken together with the atom to which they are attached form 59. The compound according to claim 58, wherein: R a ' is a (C r C 4 )alkyl, phenyl or naphthyl group, where the (C r C 4 )aUcyl group is unsubstituted or substituted with one or more substituents independently selected from halo, C r C 4 aUcoxy or C r C 4 haloalkoxy and the phenyl or naphthyl group is unsubstituted or substituted with one or more substituents independently selected from halo, C C 4 alkyl, C r C 4 haloaUcyl, C r C 4 aUcoxy, C r C 4 haloaUcoxy, methylenedioxy and phenyl, where the phenyl is unsubstituted or substituted by one or more substituents independently selected from halo, C C 4 alkyl, C r C 4 haloaUcyl, C r C 4 aUcoxy, C r C 4 haloalkoxy and methylenedioxy; n is 1 or 2; R b and R d are each H; R x is H and R y is H or substituted or unsubstituted methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, 2-propen-l-yl, 2-propen-2-yl, 2-propyn-l-yl, 3-methyl-3-buten-l-yl, -methylcyclohexyl, -methylthienyl or benzyl, where the substituted methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, 2-propen-l-yl, 2-propen-2-yl, 2-propyn-l-yl, 3 -methyl-3 -buten- 1-yl, and -methylcyclohexyl is substituted by one or more substituents independently selected from halo, alkoxy, aryloxy, aUcylthio and arylthio; the subsituted thienyl is substituted by one or more substituents independently selected from lower alkyl, lower aUcoxy, hydroxy, amino, aUcylamino, dialkylamino and halo; and the phenyl moiety ofthe substituted benzyl is substituted by one or more substituents independently selected from lower alkyl, lower aUcoxy, aUcylenedioxy, hydroxy, amino, alkylamino, diaUcylamino and halo; R c is -CH 2 CH 2 C(O)NH 2 where n is 1 ; and Z 1 is H and Z is -CO 2 CH 2 CH 3 , -CO 2 (CH(CH 3 ) 2 ), -CO 2 (C(CH 3 ) 3 ), -CO 2 CH 2 (C(CH 3 ) 3 ), -CO 2 (cyclo-C 5 H 9 ) or Z 1 and Z taken together with the atom to which they are attached form 60. The compound according to claim 58, wherein: R a ' is a halo-substituted phenyl group; n is 2; R b and R d are each H; R x is H and R y is H, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, 2-propen-l-yl, 2-propen-2-yl, 2-propyn-l-yl, 3-methyl-3-buten-l-yl, -methylcyclohexyl, benzyl or substituted benzyl, wherein the phenyl moiety ofthe substituted benzyl comprises one or more substituents independently selected from C r C 4 alkyl, C x -C 4 alkoxy and halo; R c is -CH 2 CH 2 C(O)NH 2 or and Z 1 is H and Z is -CO 2 CH 2 CH 3 or Z 1 and Z taken together with the atom to which they are attached form 61. The compound according to any one of claims 52-60, wherein R y is H, ethyl, 2-propyn-l-yl, methylcyclohexyl or benzyl. 62. An antipicornaviral compound having the formula: wherein: W is CH or N; R a' is a C r C 4 alkyl, C 3 -C 8 cycloaUcyl, aryl or heteroaryl group, where the C r C 4 alkyl, C 3 -C 8 cycloaUcyl, aryl, and heteroaryl group is unsubstituted or substituted with one or more suitable substituents, provided that R a' is not an amino-substituted alkyl group; R 4 and R 6 are each independently H or C r C 4 alkyl; R 5 is H, C r C 4 alkyl, C r C 4 haloaUcyl or an arylalkyl, heteroarylalkyl, cycloaUcylaUcyl group or a straight-chain saturated hydrocarbon moiety or an unsaturated hydrocarbon moiety, where the arylaUcyl, heteroarylalkyl, cycloaUcylaUcyl group is unsubstituted or substituted with one or more suitable substituents; R 7 is where n is 1 or 2; and Z 1 is H or C r C 4 alkyl and Z is -CO 2 -aUcyl, -CO 2 -cycloaUcyl, -CO 2 -alkylaryl or -CO 2 -aUcyUιeterocycloaryl, or Z 1 and Z taken together with the atom to which they are attached form 63. The compound according to claim 62, wherein: R a ' is a C r C 4 alkyl, C 5 -C 6 cycloaUcyl, phenyl, naphthyl or heteroaryl group, where the phenyl, naphthyl or heteroaryl group is unsubstituted or substituted with one or more substituents independently selected from halo, Cj- alkyl, - haloaUcyl, - C 4 aUcoxy, C r C 4 haloaUcoxy, methylenedioxy, aryl, heterocycloaUcyl, and heteroaryl, where the aryl, heterocycloaUcyl and heteroaryl is unsubstituted or substituted by one ore more substituents independently selected from halo, - alkyl, C r C 4 haloaUcyl, C r C 4 aUcoxy, C r C 4 haloalkoxy and methylenedioxy; R 4 and R 6 are each H; R 5 is H or substituted or unsubstituted methyl, ethyl, n-propyl, iso-propyl, n- butyl, sec-butyl, iso-butyl, 2-propen-l-yl, 2-propen-2-yl, 2-propyn-l-yl, 3-methyl-3-buten-l-yl, -methylcyclohexyl, -methylthienyl or benzyl, where the substituted methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, 2-propen-l-yl, 2-propen-2-yl, 2-propyn-l-yl, 3-methyl-3-buten-l-yl, and -methylcyclohexyl is substituted by one or more substituents independently selected from halo, alkoxy, aryloxy, alkylthio and arylthio; the subsituted thienyl is substituted by one or more substituents independently selected from lower alkyl, lower alkoxy, hydroxy, amino, aUcylamino, dialkylamino and halo; and the phenyl moiety ofthe substituted benzyl is substituted by one or more substituents independently selected from lower alkyl, lower alkoxy, aUcylenedioxy, hydroxy, amino, aUcylamino, diaUcylamino and halo; R 7 is where n is 1 ; and Z 1 is H and Z is -CO 2 CH 2 CH 3 , -CO 2 (CH(CH 3 ) 2 ), -CO 2 (C(CH 3 ) 3 ), -CO 2 CH 2 (C(CH 3 ) 3 ), -CO 2 (cyclo-C 5 H 9 ) or Z 1 and Z taken together with the atom to which they are attached form 64. The compound according to claim 62, wherein: R a ' is a C r C 4 alkyl, C 5 -C 6 cycloaUcyl, phenyl, naphthyl, pyrrolyl or indolyl, group, where the phenyl, naphthyl, pyrrolyl or indolyl, group is unsubstituted or substituted with one or more substituents independently selected from halo, C r C 4 alkyl, C r C 4 haloaUcyl, C r C 4 alkoxy, C C 4 haloaUcoxy, methylenedioxy and a phenyl, naphthyl, isoquinoyl, pyridyl or isoxazolyl group, wherein the phenyl, naphthyl, isoquinoyl, pyridyl and isoxazolyl group is unsubstituted or substituted by one ore more substituents independently selected from halo, Cj-C 4 alkyl, C r C 4 haloaUcyl, Cj-C 4 aUcoxy, C r C 4 haloaUcoxy and methylenedioxy; R 4 and R 6 are each H; R 5 is H, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, 2-propen-l-yl, 2-propen-2-yl, 2-propyn-l-yl, 3 -methyl-3 -buten- 1-yl, -methylcyclohexyl, benzyl or substituted benzyl, wherein the phenyl moiety ofthe substituted benzyl comprises one or more substituents independently selected from Cj-Q, alkyl, C r C 4 aUcoxy and halo; Z 1 is H and Z is -CO 2 CH 2 CH 3 or Z 1 and Z taken together with the atom to wliich they are attached form 65. The compound according to claim 62, having the formula: 66. The compound according to claim 62, having the formula: 67. An antipicornaviral compound having the formula: wherein: R 1 is H, halo, C r C 4 aUcyl, C r C 4 haloaUcyl, or an aryl or heteroaryl group, where the aryl or heteroaryl group is unsubstituted or substituted with one or more suitable substituents; R 2 and R 3 are each mdependently H or C r C 4 alkyl; or or R 1 together with R 2 form a cycloaUcyl, heterocycloaUcyl, aryl or heteroaryl ring, where the cycloaUcyl, heterocycloaUcyl, aryl or heteroaryl ring is unsubstituted or substituted with one or more suitable substituents; R 4 and R 6 are each independently H or C r C 4 alkyl; R 5 is H, - alkyl, C r C 4 haloaUcyl or an arylalkyl, heteroarylalkyl, cycloaUcylaUcyl group or a straight-chain saturated hydrocarbon moiety or an unsaturated hydrocarbon moiety, where the arylalkyl, heteroarylalkyl, cycloaUcylaUcyl group is unsubstituted or substituted with one or more suitable substituents; R 7 is selected from -CH 2 CH 2 C(O)NH 2 ; -CH 2 CH 2 C(O)NH-alkyl; -CH 2 NHC(O)CH 3 ; and , where n is 1 or 2; and Z 1 is H or C r C 4 aUcyl and Z is -CO 2 -aUcyl, -CO 2 -cycloaUcyl, -CO 2 -aUcylaryl or -CO 2 -alkyUιeterocycloaryl, or Z 1 and Z taken together with the atom to which they are attached form 68. The compound according to claim 67, wherein: R 1 is H, halo, C,-C 4 aUcyl, C r C 4 haloaUcyl or a phenyl, naphthyl, isoxazolyl, pyridyl, quinoyl or isoquinoyl group, where the phenyl, naphthyl, isoxazolyl, pyridyl, quinoyl or isoquinoyl group is unsubstituted or substituted with one or more substituents independently selected from: halo, C r C 4 alkyl, C r C 4 haloaUcyl, C r C 4 aUcoxy, C r C 4 haloaUcoxy and methylenedioxy; R 2 and R 3 are each H; or R 1 together with R 2 form a phenyl ring, which is unsubstituted or substituted with one or more suitable substituents and R 3 is H; R 4 and R 6 are each H; R 5 is H or substituted or unsubstituted methyl, ethyl, n-propyl, iso-propyl, n- butyl, sec-butyl, iso-butyl, 2-propen-l-yl, 2-propen-2-yl, 2-propyn-l-yl, 3 -methyl-3 -buten- 1-yl, -methylcyclohexyl, -methylthienyl or benzyl, where the substituted methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, 2-propen-l-yl, 2-propen-2-yl, 2-propyn-l-yl, 3-methyl-3-buten-l-yl, and -methylcyclohexyl is substituted by one or more substituents independently selected from halo, alkoxy, aryloxy, aUcylthio and arylthio; the subsituted thienyl is substituted by one or more substituents independently selected from lower alkyl, lower aUcoxy, hydroxy, amino, alkylamino, diaUcylamino and halo; and the phenyl moiety ofthe substituted benzyl is substituted by one or more substituents independently selected from lower aUcyl, lower aUcoxy, aUcylenedioxy, hydroxy, amino, aUcylamino, diaUcylamino and halo; R 7 is -CH 2 CH 2 C(O)NH 2 or , where n is 1 ; and Z 1 is H and Z is -CO 2 CH 2 CH 3 , -CO 2 (CH(CH 3 ) 2 ), -CO 2 (C(CH 3 ) 3 ), -CO 2 CH 2 (C(CH 3 ) 3 ), -CO 2 (cyclo-C 5 H 9 ) or Z 1 and Z taken together with the atom to which they are attached form 69. The compound according to claim 67, wherein: R 1 is H, phenyl, -naphthyl, β-naphthyl, 2-chlorophenyl, 2-α, ,α-trifluoromethylρhenyl, 3-chloro-6-methoxyphenyl, 2,3-dichlorophenyl, 4-isoquinoyl, 3-iso-propylphenyl, 2,5-dimethoxyphenyl, 2-methoxyphenyl, 2-methylphenyl, 2-bromophenyl, 3-pyridyl, 4-pyridyl, 3-methyl-isoxazol-5-yl, 3,3,3-trifluoroprop-l-yl, or 2,3-benzo[d]dioxolyl; R 2 and R 3 are each H; R 4 and R 6 are each H; R 5 is H, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, 2-propen-l-yl, 2-propen-2-yl, 2-propyn-l-yl, 3 -methyl-3 -buten- 1-yl, -methylcyclohexyl, benzyl or substituted benzyl, wherein the phenyl moiety ofthe substituted benzyl comprises one or more substituents independently selected from C x -C 4 alkyl, C r C 4 aUcoxy and halo; R 7 is -CH 2 CH 2 C(O)NH 2 or and Z 1 is H and Z is -CO 2 CH 2 CH 3 or Z 1 and Z taken together with the atom to which they are attached form 70. An antipicornaviral compound having the formula: wherein: R 1 is H, halo, - alkyl, C r C 4 haloaUcyl, or an aryl or heteroaryl group, where the aryl or heteroaryl group is unsubstituted or substituted with one or more suitable substituents; R 2 and R 3 are each mdependently H or C r C 4 alkyl; or or R 1 together with R 2 form a cycloalkyl, heterocycloaUcyl, aryl or heteroaryl ring, where the cycloaUcyl, heterocycloaUcyl, aryl or heteroaryl ring is unsubstituted or substituted with one or more suitable substituents; R 4 and R 6 are each independently H or C r C 4 alkyl; R 5 is H, Cj- alkyl, C -C 4 haloaUcyl or an arylaUcyl, heteroarylaUcyl, cycloaUcylaUcyl group or a straight-chain saturated hydrocarbon moiety or an unsaturated hydrocarbon moiety, where the arylaUcyl, heteroarylaUcyl, cycloaUcylaUcyl group is unsubstituted or substituted with one or more suitable substituents; R 7 is selected from -CH 2 CH 2 C(O)NH 2 ; -CH 2 CH 2 C(O)NH-alkyl; -CH 2 NHC(O)CH 3 ; and , where n is 1 or 2; and Z 1 is H or C r C 4 aUcyl and Z is -CO 2 -aUcyl, -CO 2 -cycloaUcyl, -CO 2 -alkylaryl or -CO 2 -aUcyUιeterocycloaryl, or Z 1 and Z taken together with the atom to which they are attached form provided that when R 1 together with R 2 form a phenyl ring and the phenyl ring is substituted, R 7 is , where n is 1 or 2.. 71. The compound according to claim 70, wherein: R 1 is H, halo, C r C 4 alkyl, C r C 4 haloaUcyl or a phenyl, naphthyl, isoxazolyl, pyridyl, quinoyl or isoquinoyl group, where the phenyl, naphthyl, isoxazolyl, pyridyl, quinoyl or isoquinoyl group is unsubstituted or substituted with one or more substituents independently selected from halo, C r C 4 alkyl, C r C 4 haloaUcyl, C r C 4 aUcoxy, C r C 4 haloalkoxy and methylenedioxy; R 2 and R 3 are each H; or R 1 together with R 2 form an unsubstituted phenyl ring and R 3 is H; R 4 and R 6 are each H; R 5 is H or substituted or unsubstituted methyl, ethyl, n-propyl, iso-propyl, n- butyl, sec-butyl, iso-butyl, 2-propen-l-yl, 2-propen-2-yl, 2-propyn-l-yl, 3-methyl-3-buten-l-yl, -methylcyclohexyl, -methylthienyl or benzyl, where the substituted methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, 2-propen-l-yl, 2-propen-2-yl, 2-propyn-l-yl, 3-methyl-3-buten-l-yl, and -methylcyclohexyl is substituted by one or more substituents independently selected from halo, aUcoxy, aryloxy, alkylthio and arylthio; the subsituted thienyl is substituted by one or more substituents independently selected from lower alkyl, lower aUcoxy, hydroxy, amino, alkylamino, diaUcylamino and halo; and the phenyl moiety ofthe substituted benzyl is substituted by one or more substituents independently selected from lower alkyl, lower alkoxy, alkylenedioxy, hydroxy, amino, aUcylamino, diaUcylamino and halo; R 7 is -CH 2 CH 2 C(O)NH 2 or , where n is 1 ; and Z 1 is H and Z is -CO 2 CH 2 CH 3 , -CO 2 (CH(CH 3 ) 2 ), -CO 2 (C(CH 3 ) 3 ), -CO 2 CH 2 (C(CH 3 ) 3 ), -CO 2 (cyclo-C 5 H 9 ) or Z 1 and Z taken together with the atom to which they are attached form 72. The compound according to claim 70, wherein: R 1 is H, phenyl, α-naphthyl, β-naphthyl, 2-chlorophenyl, 2-α,α,α-trifluoromethylphenyl, 3-chloro-6-methoxyphenyl, 2,3-dichlorophenyl, 4-isoquinoyl, 3-iso-propylphenyl, 2,5-dimethoxyphenyl, 2-methoxyphenyl, 2-methylphenyl, 2-bromophenyl, 3-pyridyl, 4-pyridyl, 3-methyl-isoxazol-5-yl, 3,3,3-trifluoroprop-l-yl, or 2,3-benzo[d]dioxolyl; R 2 and R 3 are each H; R 4 and R 6 are each H; R 5 is H, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, 2-propen-l-yl, 2-propen-2-yl, 2-propyn-l-yl, 3 -methyl-3 -buten- 1-yl, -methylcyclohexyl, benzyl or substituted benzyl, wherein the phenyl moiety ofthe substituted benzyl comprises one or more substituents independently selected from C r C 4 alkyl, Cj- aUcoxy and halo; R 7 is -CH 2 CH 2 C(O)NH 2 or ; and Z 1 is H and Z is -CO 2 CH 2 CH 3 or Z 1 and Z taken together with the atom to which they are attached form 73. An antipicornaviral compound having the formula: wherein: each R z is independently selected from halo and a C r C 4 aUcoxy, C r C 4 alkyl, aryl, heterocycloaUcyl or heteroaryl group where the C r C 4 aUcoxy or Cj- alkyl group is unsubstituted or substituted with one or more substituents independently selected from halo, C C 4 alkoxy or - haloaUcoxy and the aryl, heterocycloaUcyl or heteroaryl group is unsubstituted or substituted by one ore more substituents independently selected from halo, C r C 4 alkyl, C r C 4 haloaUcyl, C r C 4 aUcoxy, C r C 4 haloaUcoxy and methylenedioxy or two R z at adjacent positions are methylenedioxy; and n z is an integer from 1 to 4; R 3 is H, halo, C r C 4 alkoxy, unsubstituted - alkyl, C r C 4 haloaUcyl and C r C 4 alkoxyalkyl; R 4 and R 6 are each independently H or C^^ alkyl; R 5 is H, Ci-C 4 alkyl, C r C 4 haloaUcyl or an arylaUcyl, heteroarylaUcyl, cycloaUcylaUcyl group or a straight-chain saturated hydrocarbon moiety or an unsaturated hydrocarbon moiety, where the arylaUcyl, heteroarylaUcyl, cycloaUcylaUcyl group is unsubstituted or substituted with one or more suitable substituents; R 7 is , where n is 1 or 2; and Z 1 is H or C r C 4 alkyl and Z is -CO 2 -aUcyl, -CO 2 -cycloaUcyl, -CO 2 -aUcylaryl or -CO 2 -alkylheterocycloaryl, or Z 1 and Z taken together with the atom to which they are attached form 74. The compound according to claim 73, wherein each R z is independently selected from halo, C r C 4 alkoxy, unsubstituted C r C 4 alkyl, C r C 4 haloalkyl, and Cj- alkoxyalkyl and n z is an integer from 1 to 2; R 3 is H or C r C 4 alkyl; R 4 and R 6 are each H; R 5 is H or substituted or unsubstituted methyl, ethyl, n-propyl, iso-propyl, n- butyl, sec-butyl, iso-butyl, 2-propen-l-yl, 2-propen-2-yl, 2-propyn-l-yl, 3 -methyl-3 -buten- 1-yl, -methylcyclohexyl, -methylthienyl or benzyl, where the substituted methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, 2-propen-l-yl, 2-propen-2-yl, 2-propyn-l-yl, 3 -methyl-3 -buten- 1-yl, and -methylcyclohexyl is substituted by one or more substituents independently selected from halo, aUcoxy, aryloxy, aUcylthio and arylthio; the subsituted thienyl is substituted by one or more substituents independently selected from lower alkyl, lower alkoxy, hydroxy, amino, aUcylamino, diaUcylamino and halo; and the phenyl moiety ofthe substituted benzyl is substituted by one or more substituents independently selected from lower alkyl, lower aUcoxy, aUcylenedioxy, hydroxy, amino, aUcylamino, diaUcylamino and halo; R 7 is where n is 1; and Z 1 is H and Z is -CO 2 CH 2 CH 3 , -CO 2 (CH(CH 3 ) 2 ), -CO 2 (C(CH 3 ) 3 ), -CO 2 CH 2 (C(CH 3 ) 3 ), -CO 2 (cyclo-C 5 H 9 ) or Z 1 and Z taken together with the atom to which they are attached form 75. The compound according to claim 73, wherein each R z is independently selected from halo, C r C 4 aUcoxy, unsubstituted C C 4 alkyl and C C 4 haloaUcyl, and n z is 1 or 2; R 3 is H ; R 4 and R 6 are each H; R 5 is H, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, 2-propen-l-yl, 2-propen-2-yl, 2-propyn-l-yl, 3 -methyl-3 -buten- 1-yl, -methylcyclohexyl, benzyl or substituted benzyl, wherein the phenyl moiety ofthe substituted benzyl comprises one or more substituents mdependently selected from C r C 4 alkyl, C r C 4 aUcoxy and halo; Z 1 is H and Z is -CO 2 CH 2 CH 3 or Z 1 and Z taken together with the atom to which they are attached form 76. An antipicornaviral compound having the formula: wherein: R a' is a C C 4 alkyl, aryl, C 3 -C 7 cycloaUcyl, heterocycloaUcyl or heteroaryl group, where the C r C 4 alkyl, aryl, C 3 -C 7 cycloaUcyl, heterocycloaUcyl or heteroaryl group is unsubstituted or substituted with one or more substituents independently selected from alkyl, haloalkyl, aUcylenedioxy, nitro, amino, hydroxamino, alkylamino, diaUcylamino, halo, hydroxyl, aUcoxy, haloalkoxy, aryloxy, mercapto, aUcylthio or arylthio, aryl or heteroaryl, where the aryl or heteroaryl group is unsubstituted or substituted with one or more substituents independently selected from halo, C,-C 4 alkyl, C C 4 haloalkyl, C r C 4 aUcoxy, C j -Q haloaUcoxy and methylenedioxy; each R 6 is independently H or C C 4 alkyl; R 5 is H, C x -C 4 alkyl, C r C 4 haloaUcyl or an arylaUcyl, heteroarylaUcyl, cycloaUcylaUcyl group or a straight-chain saturated hydrocarbon moiety or an unsaturated hydrocarbon moiety, where the arylaUcyl, heteroarylaUcyl, cycloaUcylaUcyl group is unsubstituted or substituted with one or more suitable substituents; R 7 is selected from -CH 2 CH 2 C(O)NH 2 ; -CH 2 CH 2 C(O)NH-alkyl; -CH 2 NHC(O)CH 3 ; and , where n is 1 or 2; and Z 1 is H or C r C 4 alkyl and Z is -CO 2 -aUcyl, -CO 2 -cycloalkyl, -CO 2 -alkylaryl or -CO 2 -alkylheterocycloaryl, or Z 1 and Z taken together with the atom to which they are attached form 77. The compound according to claim 76, wherein: R a' is a C r C 4 alkyl, C r C 4 haloalkyl, phenyl, naphthyl, C 5 -C 6 cycloaUcyl, isoquinoyl, pyridyl or pyrrolyl group, where the phenyl, naphthyl, isoquinoyl, pyridyl or pyrrolyl group is unsubstituted or substituted with one or more substituents independently selected from halo, C r C 4 alkyl, C r C 4 haloaUcyl, C r C 4 aUcoxy, C r C 4 haloaUcoxy and methylenedioxy; each R 6 is H; R 5 is H or substituted or unsubstituted methyl, ethyl, n-propyl, iso-propyl, n- butyl, sec-butyl, iso-butyl, 2-propen-l-yl, 2-propen-2-yl, 2-propyn-l-yl, 3 -methyl-3 -buten- 1-yl, -methylcyclohexyl, -methylthienyl or benzyl, where the substituted methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, 2-propen-l-yl, 2-propen-2-yl, 2-propyn-l-yl, 3 -methyl-3 -buten- 1-yl, and -methylcyclohexyl is substituted by one or more substituents independently selected from halo, aUcoxy, aryloxy, aUcylthio and arylthio; the subsituted thienyl is substituted by one or more substituents independently selected from lower alkyl, lower aUcoxy, hydroxy, amino, aUcylamino, diaUcylamino and halo; and the phenyl moiety ofthe substituted benzyl is substituted by one or more substituents independently selected from lower alkyl, lower aUcoxy, alkylenedioxy, hydroxy, amino, aUcylamino, diaUcylamino and halo; R 7 is -CH 2 CH 2 C(O)NH 2 or , where n is 1 ; and Z 1 is H and Z is -CO 2 CH 2 CH 3 , -CO 2 (CH(CH 3 ) 2 ), -CO 2 (C(CH 3 ) 3 ), -CO 2 CH 2 (C(CH 3 ) 3 ), -CO 2 (cyclo-C 5 H 9 ) or Z 1 and Z taken together with the atom to which they are attached form 78. . The compound according to claim 76, wherein: R a' is a phenyl group, where the phenyl group is unsubstituted or substituted with one or more substituents mdependently selected from halo, C r C 4 alkyl, C haloaUcyl or C r C 4 aUcoxy; each R 6 is H; R 5 is H, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, 2-propen-l-yl, 2-propen-2-yl, 2-propyn-l-yl, 3 -methyl-3 -buten- 1-yl, -methylcyclohexyl, benzyl or substituted benzyl, wherein the phenyl moiety ofthe substituted benzyl comprises one or more substituents independently selected from C r C 4 alkyl, C r C 4 aUcoxy and halo; R' is -CH 2 CH 2 C(O)NH 2 or and Z 1 is H and Z is -CO 2 CH 2 CH 3 or Z 1 and Z taken together with the atom to which they are attached form 79. The compound according to any one of claims 62 to 78, where R 5 is H, ethyl, 2-propyn-l-yl, methylcyclohexyl or benzyl. 80. The compound according to any one of claims 1, 8, 9, 12, 13, 14, 19, 20, 49, 62, 67, 70, 73 or 76 having antipicornaviral activity coπesponding to an EC 50 less than or equal to 100 μM in an Hl-HeLa cell culture assay. 81. The compound according to claim 16, having antipicornaviral activity coπesponding to an EC 50 less than or equal to 100 μM in an Hl-HeLa cell culture assay. 82. A pharmaceutical composition comprising: a therapeutically effective amount of at least one antipicornaviral agent selected from compounds, prodrugs, pharmaceutically acceptable salts, pharmaceutically active metabolites, and pharmaceutically acceptable solvates defined in any one of claims 1, 8, 9, 12, 13, 14, 19, 20, 49, 62, 67, 70, 73 or 76; and a pharmaceutically acceptable carrier, diluent, vehicle, or excipient. 83. The method of treating a mammalian disease condition mediated by picomaviral protease activity, comprising administering to a mammal in need thereof a therapeutically effective amount of at least one compound, prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate defined in anyone of claims 1, 8, 9, 12, 13, 14, 19, 20, 49, 62, 67, 70, 73 or 76. 84. The method of inhibiting the activity of a picomaviral 3C protease, comprising contacting the picomaviral 3C protease with an effective amount of at least one compound, prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate defined in any one of claims 1, 8, 9, 12, 13, 14, 19, 20, 49, 62, 67, 70, 73 or 76. 85. The method as defined in claim 53, wherein the picomaviral 3C protease is a rhinoviral protease. 86. A compound selected from: . 87. The compound according to claim 86, selected from, the group consisting of: and

Inventors: DRAGOVICH PETER S, HUA YE, JOHNSON THEODORE O JR, LUU HIEP T, DRAGOVICH, PETER, S., HUA, YE, JOHNSON, THEODORE, O., JR., LUU, HIEP, T.
Applicants: AGOURON PHARMA, AGOURON PHARMACEUTICALS, INC.
Application year: 2001
Main classification: C07D207
IPC codes: A61K31, A61K38, A61P31, A61P43, C07D207, C07D401, C07D403, C07D405, C07D413, C07K5