Patent ID: 6455522
Filing Date: 2002-09-24
Classification: A61P,C07D

Abstract:
A compound of formula I: or a stereoisomer or pharmaceutically acceptable salt form thereof, wherein;A is selected from COR5, â€”CO2H, CH(R)CO2H, â€”CO2R6, â€”CONHOH, â€”CH(R)CONHOH, â€”CONHOR5, â€”CONHOR6, â€”NHRa, â€”N(OH)COR5, â€”SH, â€”CH2SH, â€”SONHRa, SN2H2Ra, PO(OH)2, and PO(OH)NHRa; ring B is a 5-10 membered cyclic sulfonamiide containing from 0-2 additional heteroatoms selected from O, NRb, and S(O)p, 0-1 carbonyl groups and 0-1 double bonds and ring B is substituted with 0-1 Rbâ€²; ring C is phenyl R1 is selected from H, Q, C1-10 alkylene-Q, C2-10 alkenylene-Q, C2-10 alkynylene-Q, (CRRâ€²)râ€²O(CRRâ€²)râ€”Q, (CRRâ€²)râ€²NRa(CRRâ€²)râ€”Q, (CRRâ€²)rC(O)(CRRâ€²)râ€”Q, (CRRâ€²)rC(O)O(CRRâ€²)râ€”Q, (CRRâ€²)râ€²OC(O)(CRRâ€²)râ€”Q, (CRRâ€²)rC(O)NRa(CRRâ€²)râ€”Q, (CRRâ€²)râ€²NRaC(O)(CRRâ€²)râ€”Q, (CRRâ€²)râ€²OC(O)O(CRRâ€²)râ€”Q, (CRRâ€²)râ€²OC(O)NRa(CRRâ€²)râ€²â€”Q, (CRRâ€²)râ€²NRaC(O)O(CRRâ€²)râ€”Q, (CRRâ€²)rNRaC(O)NRa(CRRâ€²)râ€”Q, (CRRâ€²)râ€²S(O)p(CRRâ€²)râ€”Q, (CRRâ€²)râ€²SO2NRa(CRRâ€²)râ€”Q, (CRRâ€²)râ€²NRaSO2(CRRâ€²)râ€”Q, (CRRâ€²)râ€²NRaSO2NRa(CRRâ€²)râ€”Q, (CRRâ€²)râ€²NRaC(O)(CRRâ€²)râ€³NHQ, (CRRâ€²)râ€²NRaC(O)(CRRâ€²)rNHC(O)ORa, and (CRRâ€²)râ€²NRaC(O)(CRRâ€²)rNHC(O)(CRRâ€²)rNHC(O)ORa; R, at each occurrence, is independently selected from H, CH3, CH2CH3, CH(CH3)2, CH&boxH;CH2, CH&boxH;CHCH3, and CH2CH&boxH;CH2; Râ€², at each occurrence, is independently selected from H, CH3, CH2CH3, and CH(CH3)2; alternatively, R and Râ€² together with the carbon to which they are attached form a cyclopropyl, cyclobutyl or cyclopentyl group; Q, at each occurence, is selected from H, a C3-13 carbocyclic residue substituted with 0-5 Rc and a 5-14 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S and substituted with 0-5 Rc; R2 is selected from H, C1-10 alkylene-H, C2-10 alkenylene-H, C2-10 alkynylene-H, (CRRâ€²)râ€²O(CRRâ€²)râ€”H, (CRRâ€²)râ€²NRa(CRRâ€²)râ€”H, (CRRâ€²)râ€²C(O)(CRRâ€²)râ€”H, (CRRâ€²)râ€²C(O)O(CRRâ€²)râ€”H, (CRRâ€²)râ€²OC(O)(CRRâ€²)râ€”H, (CRRâ€²)râ€²C(O)NRa(CRRâ€²)râ€”H, (CRRâ€²)râ€²NRaC(O)(CRRâ€²)râ€”H, (CRRâ€²)râ€²OC(O)O(CRRâ€²)râ€”H, (CRRâ€²)râ€²OC(O)NRa(CRRâ€²)râ€”H, (CRRâ€²)râ€²NRaC(O)O(CRRâ€²)râ€”H, (CRRâ€²)râ€²NRaC(O)NRa(CRRâ€²)râ€”H, (CRRâ€²)râ€²S(O)p(CRRâ€²)râ€”H, (CRRâ€²)râ€²SO2NRa(CRRâ€²)râ€”H, (CRRâ€²)râ€²NRaSO2(CRRâ€²)râ€”H, and (CRRâ€²)râ€²NRaSO2NRa(CRRâ€²)râ€”H; R3 is Uâ€”Xâ€”Yâ€”X1â€”Z; U is absent or is selected from: O, NRa, C(O), C(O)O, OC(O), C(O)NRa, NRaC(O), OC(O)O, OC(O)NRa, NRaC(O)O, NRaC(O)NRa, S(O)p, S(O)pNRa, NRaS(O)p, and NRaSO2NRa; X is absent or selected from C1-10 alkylene, C2-10 alkenylene, and C2-10 alkynylene; X1 is absent or selected from C1-10 alkylene, C2-10 alkenylene, and C2-10 alkynylene; Y is absent or selected from O, NRa, S(O)p, S(O)pNRa, C(O)NRa, and C(O), provided that when U and Y are present, X is present; Z is selected from H, a C3-13 carbocyclic residue substituted with 0-5 Rd and a 5-14 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S and substituted with 0-5 Rd; R4, at each occurence, is selected from C1-6 alkyl, ORa, Cl, F, Br, I, &boxH;O, CN, NO2, NRaRaâ€², C(O)Ra, C(O)ORa, C(O)NRaRaâ€², RaNC(O)NRaRaâ€², OC(O)NRaRaâ€², RaNC(O)O, S(O)2NRaRaâ€², NRaS(O)2Raâ€³, NRaS(O)2NRaRaâ€², OS(O)2NRaRaâ€², NRaS(O)2O, S(O)pRaâ€³, CF3, CF2CF3, C3-6 carbocyclic residue, and a 5-10 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S; Ra, at each occurrence, is independently selected from H, C1-4 alkyl, phenyl or benzyl; Raâ€², at each occurrence, is independently selected from H, C1-4 alkyl, phenyl or benzyl; Raâ€³, at each occurrence, is independently selected from C1-4 alkyl, phenyl or benzyl; alternatively, Ra and Raâ€²taken together with the nitrogen to which they are attached form a 5 or 6 membered ring containing from 0-1 additional heteroatoms selected from the group consisting of N, O, and S; Rb is selected from H, C1-6 alkyl, phenyl, benzyl, C(O)Ra, C(O)NRaRaâ€², S(O)2NRaRaâ€², and S(O)pRaâ€³; Rbâ€²is selected from H, Q, C1-10 alkylene-Q, C2-10 alkenylene-Q, C2-10 alkynylene-Q, (CRRâ€²)râ€²O(CRRâ€²)râ€”Q, (CRRâ€²)râ€²NRa(CRRâ€²)râ€”Q, (CRRâ€²)rC(O)(CRRâ€²)râ€²â€”Q, (CRRâ€²)rC(O)O(CRRâ€²)râ€”Q, (CRRâ€²)râ€²OC(O)(CRRâ€²)râ€”Q, (CRRâ€²)rC(O)NRa(CRRâ€²)râ€”Q, (CRRâ€²)râ€²NRaC(O)(CRRâ€²)râ€”Q, (CRRâ€²)râ€²OC(O)O(CRRâ€²)râ€”Q, (CRRâ€²)râ€²OC(O)NRa(CRRâ€²)râ€”Q, (CRRâ€²)râ€²NRaC(O)O(CRRâ€²)râ€”Q, (CRRâ€²)râ€²NRaC(O)NRa(CRRâ€²)râ€”Q, (CRRâ€²)râ€²S(O)p(CRRâ€²)râ€”Q, (CRRâ€²)râ€²SO2NRa(CRRâ€²)râ€”Q, (CRRâ€²)râ€²NRaSO2(CRRâ€²)râ€”Q, (CRRâ€²)râ€²NRaSO2NRa(CRRâ€²)râ€”Q, (CRRâ€²)râ€²NRaC(O)(CRRâ€²)râ€³NHQ, (CRRâ€²)râ€²NRaC(O)(CRRâ€²)rNHC(O)ORa, and (CRRâ€²)râ€²NRaC(O)(CRRâ€²)rNHC(O)(CRRâ€²)rNHC(O)ORa; Rc, at each occurrence, is independently selected from C1-6 alkyl, ORa, Cl, F, Br, I, &boxH;O, CN, NO2, NRaRaâ€², C(O)Ra, C(O)ORa, C(O)NRaRaâ€², NRaC(O)NRaRaâ€², OC(O)NRaRaâ€², RaNC(O)O, S(O)2NRaRaâ€², NRaS(O)2Raâ€³, NRaS(O)2NRaRaâ€², OS(O)2NRaRaâ€², NRaS(O)2O, S(O)pRaâ€³, CF3, CF2CF3, â€”CH(&boxH;NOH), â€”C(&boxH;NOH)CH3, (CRRâ€²)sO(CRRâ€²)sâ€²Rcâ€², (CRRâ€²)sS(O)p(CRRâ€²)sâ€²Rcâ€², (CRRâ€²)sNRa(CRRâ€²)sâ€²Rcâ€², 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; Rcâ€², at each occurrence, is independently selected from phenyl substituted with 0-3 Rb, biphenyl substituted with 0-2 Rb, naphthyl substituted with 0-3 Rb and a 5-10 membered heteroaryl system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S and substituted with 0-3 Rb; Rd, at each occurrence, is independently selected from C1-6 alkyl, ORa, Cl, F, Br, I, &boxH;O, CN, NO2, NRaRaâ€², C(O)Ra, C(O)ORa, C(O)NRaRaâ€², NRaC(O)NRaRaâ€², OC(O)NRaRaâ€², NRaC(O)O, S(O)2NRaRaâ€², NRaS(O)2Raâ€³, NRaS(O)2NRaRaâ€², OS(O)2NRaRaâ€², NRaS(O)2O, S(O)pRaâ€³, CF3, CF2CF3, 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; R5, at each occurrence, is selected from H, C1-10 alkyl substituted with 0-2 Re, and C1-8 alkyl substituted with 0-2 Rf; Re, at each occurrence, is independently selected from C1-6 alkyl, ORa, Cl, F, Br, I, &boxH;O, CN, NO2, NRaRaâ€², C(O)Ra, C(O)ORa, C(O)NRaRaâ€², S(O)2NRaRaâ€², S(O)pRaâ€³, CF3, and CF2CF3; Rf, at each occurrence, is selected from phenyl substituted with 0-2 Re and biphenyl substituted with 0-2 Re; R6, at each occurrence, is selected from 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-aryl-1,3-dioxa-cyclopenten-2-one-yl)methyl, â€”C1-10 alkyl-NR7R7a, â€”CH(R8)OC(&boxH;O)R9, â€”CH(R8)OC(&boxH;O)OR9, and R7 is selected from H and C1-10 alkyl, C2-6 alkenyl, C3-6 cycloalkyl-C1-3 alkyl-, and phenyl-C1-6 alkyl-; R7a is selected from H and C1-10 alkyl, C2-6 alkenyl, C3-6 cycloalkyl-C1-3 alkyl-, and phenyl-C1-6 alkyl-; R8 is selected from H and C1-4 linear alkyl; R9 is selected from H, C1-8 alkyl substituted with 1-2 Rg, C3-8 cycloalkyl substituted with 1-2 Rg, and phenyl substituted with 0-2 Re; Rg, at each occurrence, is selected from C1-4 alkyl, C3-8 cycloalkyl, C1-5 alkoxy, phenyl substituted with 0-2 Re; p, at each occurrence, is selected from 0, 1, and 2; r, at each occurrence, is selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; râ€², at each occurrence, is selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; and, s, at each occurence, is selected from 0, 1, 2, and 3.