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1. A compound of the formula IA: its enantiomers, diastereomers, enantiomerically enriched mixtures, racemic mixtures thereof, prodrugs, crystalline forms, non-crystalline forms, amorphous forms thereof, solvates thereof, metabolites thereof, and pharmaceutically acceptable salts, wherein: ring A is a 3-13 membered carbocycle or heterocycle comprising carbon atoms, 0-3 carbonyl groups, 0-4 double bonds, and from 0-4 ring heteroatoms selected from the group consisting of O, N, NR, and S(O)p, provided that ring A contains other than a S—S, O—O, or S—O bond; n′ is an integer from 1-3; Z is selected from the group consisting of COR5, CO2H, —CH2CO2H, —CO2R6, —CONHOH, —CONHOR5, —CON(R6)OH, —CONHOR6, —NHRa, —N(OH)C(O)R5, —N(OH)CHO, —SH, —CH2SH, —S(O)(═NH)Ra, —SN2H2Ra, —PO(ORg)2, —PO(OH)NHRa, Rg is independently selected from the group consisting of H, CH2OCORa, P is D-E-G-Q-L-T-X-Y, wherein D is absent or is selected from the group consisting of O, NRa1, C(O), C(O)O, OC(O), C(O)NRa1, NRa1C(O), OC(O)O, OC(O)NRa1, NRa1C(O)O, NRa1C(O)NRa1, S(O)p, S(O)pNRa1, NRa1S(O)p, and NRa1SO2NRa1; E is absent or is selected from the group consisting of C1-10alkylene, C2-10 alkenylene, and C2-10 alkynylene; G is absent or is selected from the group consisting of O, NRa1, S(O)p, and C(O); Q is absent or is selected from the group consisting of a C3-13 carbocycle substituted with 0-5 Rb, and a 5-14 membered heterocycle comprising carbon atoms and 1-4 heteroatoms selected from the group consisting of N, O, and S(O)p, and said heterocycle being substituted with 0-5 Rb; L is absent or is selected from the group consisting of O, NRa1, C(O), C(O)O, OC(O), C(O)NRa1, NRa1C(O), OC(O)O, OC(O)NRa1, NRa1C(O)O, NRa1C(O)NRa1, S(O)p, S(O)pNRa1, NRa1S(O)p, and NRa1SO2NRa1; T is absent or is selected from the group consisting of C1-10 alkylene, C2-10 alkenylene, and C2-10 alkynylene; X is absent or is selected from the group consisting of O, NRa1, S(O)p, and C(O); Y is selected from the group consisting of H, a C3-13 carbocycle substituted with 0-5 Rc and a 5-14 membered heterocycle comprising carbon atoms and 1-4 heteroatoms selected from the group consisting of N, O, and S(O)p, and said heterocycle being substituted with 0-5 Rc; provided that D, E, G, Q, L, T, X and Y do not combine to form a N—N, N—O, O—N, O—O, S(O)p—O, O—S(O)p or S(O)p—S(O)p group; R, at each occurrence, is independently selected from (C1-10 alkylene substituted with 1-3 Rb1)-M, (C2-10 alkenylene substituted with 1-3 Rb1)-M, (C2-10 alkynylene substituted with 1-3 Rb1)-M, OH, Cl, F, Br, I, —CN, NO2, CF3, CF2CF3, CH2F, CHF2, CF2CH3, C(CH3)2F, OCF3, OCF2CF3, OCHF2, O(CRdRd1)r-M, NRa(CRdRd1)r-M, OC(O)(CRdRd1)r-M, NRaC(O)(CRdRd1)r-M, OC(O)O(CRdRd1)r-M, OC(O)NRa(CRdRd1)r-M, NRaC(O)O(CRdRd1)r-M, NRaC(O)NRa1(CRdRd1)r-M, S(O)p(CRdRd1)r-M, S(O)2NRa(CRdRd1)r-M, NRaS(O)2(CRdRd1)r-M, and NRaS(O)2NRa1(CRdRd1)r-M, (CRdRd1)rP(O)(ORa)2, (CRdRd1)rP(O)(ORa)(NRdRd1), (CRdRd1)rP(O)(NRaRa1)2, (CRdRd1)rOP(O)(ORa)2, (CRdRd1)rOP(O) (ORa)(NRaRa1), (CRdRd1)rOP(O)(NRaRa1)2, (CRdRd1)rNRaP(O)(ORa)2, (CRdRd1)rNRaP(O)(ORa)(NRaRa1), (CRdRd1)rNRaP(O)(NRaRa1)2; C(═NRa)NRa1Ra2; C(═CRdRd1)NRa1Ra2; a C3-13 carbocycle substituted with 0-5 Rd, and a 5-14 membered heterocycle comprising carbon atoms and 1-4 heteroatoms selected from the group consisting of N, O, S(O)p and said heterocycle being substituted with 0-5 Rd; alternatively, two R, together with a carbon atom on A, form the group CA═CRdRd1, where the atom CA is said atom on A; M is selected from the group consisting of H, C2-10 alkenylene substituted with 0-3 Rb1, C2-10 alkynylene substituted with 0-3 Rb1, ORa, Cl, F, Br, I, —CN, NO2, NRaRa1, C(O)Ra, C(O)ORa, C(O)NRaRa1, RaNC(O)NRaRa1, OC(O)NRaRa1, NRaC(O)ORa, NRaC(O)Ra, S(O)2NRaRa1, NRaS(O)2Ra2, NRaS(O)2NRaRa1, OS(O)2NRaRa1, S(O)pRa2, CF3, CF2CF3, CH2F, CHF2, CF2CH3, C(CH3)2F, OCF3, OCF2CF3, OCHF2, a C3-13 carbocycle substituted with 0-5 Rd, and a 5-14 membered heterocycle comprising carbon atoms and 1-4 heteroatoms selected from the group consisting of N, O, S(O)p and said heterocycle being substituted with 0-5 Rd; alternatively, R, at each occurrence, is independently selected from (CRdRd1)rO(CRdRd1)r-M1, (CRdRd1)rNRa(CRdRd1)r-M1, (CRdRd1)rC(O)(CRdRd1)r-M1, (CRdRd1)rC(O)O(CRdRd1)r-M1, (CRdRd1)rOC(O)(CRdRd1)r-M1, (CRdRd1)rC(O)NRa(CRdRd1)r-M1, (CRdRd1)rNRaC(O)(CRdRd1)r-M1, (CRdRd1)rOC(O)O(CRdRd1)r-M1, (CRdRd1)rOC(O)NRa(CRdRd1)r-M1, (CRdRd1)rNRaC(O)O(CRdRd1)r-M1, (CRdRd1)rNRaC(O)NRa1(CRdRd1)r-M1, (CRdRd1)rS(O)p(CRdRd1)r-M1, (CRdRd1)rS(O)2NRa(CRdRd1)r-M1, (CRdRd1)rNRaS(O)2(CRdRd1)r-M1, and (CRdRd1)rNRaS(O)2NRa1(CRdRd1)r-M1; M1 is selected from the group consisting of C1-10 alkylene-M1, C2-10 alkenylene-M1, C2-10 alkynylene-M1, ORa, Cl, F, Br, I, —CN, NO2, NRaRa1, C(O)Ra, C(O)ORa, C(O)NRaRa1, RaNC(O)NRaRa1, OC(O)NRaRa1, RaNC(O)ORa1, S(O)2NRaRa1, NRaS(O)2Ra2, NRaS(O)2NRaRa1, OS(O)2NRaRa1, S(O)pRa2, CF3, CF2CF3, CH2F, CHF2, CF2CH3, C(CH3)2F, OCF3, OCF2CF3, and a 5-14 membered non-aromatic heterocycle comprising carbon atoms and 1-4 heteroatoms selected from the group consisting of N, O, S(O)p and said heterocycle being substituted with 0-5 Rd; a C3-C13 carbocycle, C4-C14 heterocycle and wherein said C3-C13 carbocycle and C4-C14 heterocycle are substituted with 1-3 Rh, and CF3, CF2CF3, CH2F, CHF2, CF2CH3, C(CH3)2F, OCF3, OCHF2, OCF2CF3 and OCH2CF3; alternatively, when two R groups are attached to adjacent ring A atoms, together with the atoms to which they are attached they may form a 3-8 membered saturated, partially saturated or unsaturated ring comprised of carbon atoms and 0-3 heteroatoms selected from the group consisting of N, NRa, O, and S(O)p, wherein said ring may be benzene-fused and/or substituted with Rd; alternatively, when two R groups are attached to the same ring A carbon, together with the carbon to which they are attached they may form a 3-8 membered saturated, partially saturated or unsaturated spiro-ring comprised of carbon atoms and 0-3 heteroatoms selected from the group consisting of N, NRa, O, and S(O)p, wherein said spiro-ring may be benzene-fused and/or substituted with Rd; provided that either two or more R or M, M1 and the atom to which they are attached do not combine to form a N—N, N—O, O—N, O—O, N-halogen, O-halogen, S-halogen, S(O)p—O, O—S(O)p, S(O)p—S(O)p group, or C(O)F, C(O)Cl, C(O)Br, or C(O)I reactive group; Ra, Ra1, and Ra2 at each occurrence are independently selected from the group consisting of H, C1-C8alkyl, C2-C8 alkenyl, C2-C8 alkynyl, wherein said alkyl, alkenyl and alkynyl groups are optionally substituted with O(primary, secondary, or tertiary)C1-C8, OH, Cl, F, Br, I, ═O, —CN, NO2, alkylamino, dialkylamino, alkarylamino, arylamino, alkylcarbonyl, aralkylcarbonyl, arylcarbonyl, carboxyl, alkylcarboxylate, alkylamido, dialkylamido, alkylureidoalkyl, alkylureidodialkyl, carbamoylalkyl, carbamoyldialkyl, alkylcarbamoyl, sulfonamidoalkyl, sulfonamidodialkyl, N-alkylsulfonamidoalkyl, N-alkylsulfonamidoalkyl, N-alkylsufonamidodialkyl, alkylamidosulfonate, dialkylamidosulfonate, alkylsulfinyl, alkylsulfonyl, CF3, CF2CF3, CH2F, CHF2, CF2CH3, C(CH3)2F, OCF3, OCF2CF3 and OCH2CF3; C3-C10 carbocycle, heterocycles, C3-C10 carbocyclylalkyl, heterocyclylalkyl and wherein said C3-C10 carbocycle, heterocycles, C3-C10 carbocyclylalkyl, and heterocyclylalkyl may be optionally substituted with one or more substituents selected from the group consisting of C1-C8 alkyl, O(primary, secondary, or tertiary)C1-C8, OH, Cl, F, Br, I, ═O, —CN, NO2, alkylamino, dialkylamino, alkarylamino, arylamino, alkylcarbonyl, aralkylcarbonyl, arylcarbonyl, carboxyl, alkylcarboxylate, alkylamido, dialkylamido, alkylureidoalkyl, alkylureidodialkyl, carbamoylalkyl, carbamoyldialkyl, alkylcarbamoyl, sulfonamidoalkyl, sulfonamidodialkyl, N-alkylsulfonamidoalkyl, N-alkylsulfonamido-alkyl, N-alkylsufonamidodialkyl, alkylamidosulfonate, dialkylamidosulfonate, alkylsulfinyl, alkylsulfonyl, CF3, CF2CF3, CH2F, CHF2, CF2CH3, C(CH3)2F, OCF3, OCF2CF3 and OCH2CF3; alternatively, Ra and Ra1 taken together with the nitrogen to which they are attached form a 4 to 8 membered ring containing from 0-1 additional heteroatoms selected from the group consisting of N, O, and S, wherein said ring may be substituted with Rd; Rb at each occurrence is independently selected from the group consisting of C1-6 alkyl optionally substituted with Rc1, O(primary, secondary, or tertiary)C1-C8, OH, Cl, F, Br, I, ═O, —CN, NO2, NRaRa1, C(O)Ra, C(O)ORa, C(O)NRaRa1, RaNC(O)NRaRa, OC(O)NRaRa1, RaNC(O)ORa1, S(O)2NRaRa1, NRaS(O)2Ra2, NRaS(O)2NRaRa1, OS(O)2NRaRa1, S(O)pRa2, CF3, CF2CF3, CH2F, CHF2, CF2CH3, C(CH3)2F, OCF3, OCHF2, OCF2CF3 and OCH2CF3; C3-10 carbocyclic residue, and a 5-14 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S, C3-C10 carbocyclyl(C1-8)alkyl, and 5-14 heterocyclyl-(C1-8)alkyl and said C3-10 carbocyclic residue, heterocyclic system, C3-C10 carbocyclyl(C1-8)alkyl, and 5-14 heterocyclyl(C1-8)alkyl are optionally substituted with Rc1; Rb1 at each occurrence is independently selected from the group consisting of ORa, F, ═O, —CN, NO2, NRaRa1 and S(O)pRa; Rc at each occurrence is independently selected from the group consisting of C1-6 alkyl optionally substituted with Rc1, ORa, Cl, F, Br, I, ═O, —CN, NO2, NRaRa1, C(O)Ra, C(O)ORa, C(O)NRaRa1, RaNC(O)NRaRa, OC(O)NRaRa1, RaNC(O)ORa1, S(O)2NRaRa1, NRaS(O)2Ra2, NRaS(O)2NRaRa1, OS(O)2NRaRa1, S(O)pRa2, CF3, CF2CF3, CH2F, CHF2, CF2CH3, C(CH3)2F, OCF3, OCHF2, OCF2CF3 and OCH2CF3; a C3-10 carbocyclic residue, and a 5-14 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S, C3-C10 carbocyclyl(C1-8)alkyl, and 5-14 heterocyclyl(C1-8)alkyl; said C3-10 carbocyclic residue, heterocyclic system C3-C10 carbocyclyl(C1-8)alkyl, and 5-14 heterocyclyl(C1-8) alkyl are optionally substituted with Rc1; Rc1 at each occurrence is independently selected from the group consisting of C1-6 alkyl, ORa, Cl, F, Br, I, ═O, —CN, NO2, NRaRa1, C(O)Ra, C(O)ORa, C(O)NRaRa1, OC(O)NRaRa1, RaNC(O)ORa, S(O)2NRaRa1, NRaS(O)2Ra2, NRaS(O)2NRaRa1, S(O)pRa2, CF3, and CF2CF3, CH2F, and CHF2; Rd at each occurrence is independently selected from the group consisting of H, C1-6 alkyl optionally substituted with Rc1, ORa, Cl, F, Br, I, ═O, —CN, NO2, NRaRa1, C(O)Ra, C(O)ORa, C(O)NRaRa1, RaNC(O)NRaRa, OC(O)NRaRa1, RaNC(O)O Ra1, S(O)2NRaRa1, NRaS(O)2Ra2, NRaS(O)2NRaRa1, OS(O)2NRaRa1, S(O)pRa2, CF3, CF2CF3, CH2F, CHF2, CF2CH3, C(CH3)2F, OCF3, OCHF2, OCF2CF3 and OCH2CF3; C3-10 carbocyclic residue, and a 5-14 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S, C3-C10 carbocyclyl(C1-8)alkyl, and 5-14 heterocyclyl(C1-8)alkyl; said C3-10 carbocyclic residue, heterocyclic system C3-C10 carbocyclyl(C1-8)alkyl, and 5-14 heterocyclyl(C1-8) alkyl optionally substituted with Rc1; Rd1 at each occurrence is independently selected from the group consisting of H, C1-6 alkyl optionally substituted with Rc1, ORa, Cl, F, Br, I, ═O, —CN, NO2, NRaRa1, C(O)Ra, C(O)ORa, C(O)NRaRa1, RaNC(O)NRaRa, OC(O)NRaRa1, RaNC(O)O Ra1, S(O)2NRaRa1, NRaS(O)2Ra2, NRaS(O)2NRaRa1, OS(O)2NRaRa1, S(O)pRa2, CF3, CF2CF3, CH2F, CHF2, CF2CH3, C(CH3)2F, OCF3, OCHF2, OCF2CF3 and OCH2CF3; C3-10 carbocyclic residue, and a 5-14 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S, C3-C10 carbocyclyl(C1-8)alkyl, and 5-14 heterocyclyl(C1-8)alkyl; said C3-10 carbocyclic residue, heterocyclic system C3-C10 carbocyclyl(C1-8)alkyl, and 5-14 heterocyclyl(C1-8) alkyl optionally substituted with Rc1; alternatively, Rd and Rd1 taken together with the atom to which they are attached form a 4 to 8 membered ring containing from 0-1 heteroatoms selected from the group consisting of N, O, and S, wherein said ring may be substituted with Rd; Rh at each occurrence is independently selected from the group consisting of ORj, NRjRa, CORj, C(O)ORj, C(O)NRjRa, NRaC(O)NRjRa1, OC(O)NRjRa, S(O)pNRjRa1, NRaS(O)pRj, NRaS(O)pNRjRa, C1-6 alkyl substituted with Rc; Rj at each occurrence is independently selected from the group consisting of CF3, CHF2, CFH2, CF2CF3, C1-C8 alkyl substituted with O(primary, secondary, or tertiary)C1-C8, OH, Cl, F, Br, I, ═O, —CN, NO2, alkylamino, dialkylamino, alkarylamino, arylamino, alkylcarbonyl, aralkylcarbonyl, arylcarbonyl, carboxyl, alkylcarboxylate, alkylamido, dialkylamido, alkylureidoalkyl, alkylureidodialkyl, carbamoylalkyl, carbamoyldialkyl, alkylcarbamoyl, sulfonamidoalkyl, sulfonamidodialkyl, N-alkylsulfonamidoalkyl, N-alkylsulfonamidoalkyl, N-alkylsufonamidodialkyl, alkylamidosulfonate, dialkylamidosulfonate, alkylsulfinyl, alkylsulfonyl, CF3, CF2CF3, CH2F, CHF2, CF2CH3, C(CH3)2F, OCF3, OCHF2, OCF2CF3 and OCH2CF3; C2-C8 alkenyl, C2-C8 alkynyl, wherein said alkenyl and alkynyl groups are optionally substituted with C1-C8alkyl, O(primary, secondary, or tertiary)C1-C8, OH, Cl, F, Br, I, ═O, —CN, NO2, alkylamino, dialkylamino, alkarylamino, arylamino, alkylcarbonyl, aralkylcarbonyl, arylcarbonyl, carboxyl, alkylcarboxylate, alkylamido, dialkylamido, alkylureidoalkyl, alkylureidodialkyl, carbamoylalkyl, carbamoyldialkyl, alkylcarbamoyl, sulfonamidoalkyl, sulfonamidodialkyl, N-alkylsulfonamidoalkyl, N-alkylsulfonamidoalkyl, N-alkylsufonamidodialkyl, alkylamidosulfonate, dialkylamidosulfonate, alkylsulfinyl, alkylsulfonyl, CF3, CF2CF3, CH2F, CHF2, CF2CH3, C(CH3)2F, OCF3, OCHF2, OCF2CF3 and OCH2CF3; C3-C10 carbocycle, heterocycles, C3-C10 carbocyclylalkyl, heterocyclylalkyl and wherein said C3-C10 carbocycle, heterocycles, C3-C10 carbocyclylalkyl, and heterocyclylalkyl may be optionally substituted with one or more substituents selected from the group consisting of O(primary, secondary, or tertiary)C1-C8, OH, Cl, F, Br, I, ═O, —CN, NO2, alkylamino, dialkylamino, alkarylamino, arylamino, alkylcarbonyl, aralkylcarbonyl, arylcarbonyl, carboxyl, alkylcarboxylate, alkylamido, dialkylamido, alkylureidoalkyl, alkylureidodialkyl, carbamoylalkyl, carbamoyldialkyl, alkylcarbamoyl, sulfonamidoalkyl, sulfonamidodialkyl, N-alkylsulfonamidoalkyl, N-alkylsulfonamido-alkyl, N-alkylsufonamidodialkyl, alkylamidosulfonate, dialkylamidosulfonate, alkylsulfinyl, alkylsulfonyl, CF3, CF2CF3, CH2F, CHF2, CF2CH3, C(CH3)2F, OCF3, OCF2CF3 and OCH2CF3, with the proviso that said C3-C10 carbocycle can not be a phenyl group and C3-C10 carbocyclylalkyl can not be a benzyl group; R3 is H or C1-6 alkyl ORa, NRaRa1, and S(O)pRa; R4 is selected from the group consisting of H, C1-6 alkyl, ORa, NRaRa1, and S(O)pRa; R5 at each occurrence is selected from the group consisting of C1-10 alkyl substituted with 0-2 Rb, and C1-8 alkyl substituted with 0-2 Re; Re at each occurrence is selected from the group consisting of phenyl substituted with 0-2 Rb and biphenyl substituted with 0-2 Rb; R6 at each occurrence is selected from the group consisting of phenyl, naphthyl, C1-10 alkyl-phenyl-C1-6 alkyl-, C3-11 cycloalkyl, C1-6 alkylcarbonyloxy-C1-3 alkyl-, C1-6 alkoxycarbonyloxy-C1-3 alkyl-, C2-10 alkoxycarbonyl, C3-6 cycloalkylcarbonyloxy-C1-3 alkyl-, C3-6 cycloalkoxycarbonyloxy-C1-3 alkyl-, C3-6 cycloalkoxycarbonyl, phenoxycarbonyl, phenyloxycarbonyloxy-C1-3 alkyl-, phenylcarbonyloxy-C1-3 alkyl-, C1-6 alkoxy-C1-6 alkylcarbonyloxy-C1-3 alkyl-, [5-(C1-C5 alkyl)-1,3-dioxa-cyclopenten-2-one-yl]methyl, [5-(Ra)-1,3-dioxa-cyclopenten-2-one-yl]methyl, (5-aryl-1,3-dioxa-cyclopenten-2-one-yl)methyl, —C1-10 alkyl-NR7R7a, —CH(R8)OC(O)R9, and —CH(R8)OC(O)OR9; alternatively, R4 and R6 can be taken together to form a 5-10 membered ring optionally substituted with Rc; R7 is selected from the group consisting of H, C1-10 alkyl, C2-6 alkenyl, C3-6 cycloalkyl-C1-3 alkyl-, and phenyl-C1-6 alkyl-; R7a is selected from the group consisting of H, C1-10 alkyl, C2-6 alkenyl, C3-6 cycloalkyl-C1-3 alkyl-, and phenyl-C1-6 alkyl-; R8 is selected from the group consisting of H and C1-4 linear alkyl; R9 is selected from the group consisting of H, C1-8 alkyl substituted with 1-2 Rf, C3-8 cycloalkyl substituted with 1-2 Rf, and phenyl substituted with 0-2 Rb; Rf at each occurrence is selected from the group consisting of H, C1-4 alkyl, Ca-8 cycloalkyl, C1-5 alkoxy, and phenyl substituted with 0-2 Rb; p at each occurrence is 0, 1, and 2; and r at each occurrence is 0, or an integer from 1 to 10. |
