Patent ID: 6399644
Filing Date: 2002-06-04
Classification: A61P,C07D

Abstract:
A compound of formula I: or a stereoisomer or pharmaceutically acceptable salt thereof, wherein;ring D is absent; ring E is selected from phenyl, pyridyl, pyrimidyl, pyrazinyl, and pyridazinyl, and ring E is substituted with G and Râ€²; G is selected from F, Cl, Br, I, OH, C1-3 alkoxy, CN, C(&boxH;NR8)NR7R9, NHC(&boxH;NR8)NR7R9, NR8CH(&boxH;NR7), C(O)NR7R8, (CR8R9)tNR7R8, SH, C1-3 alkyl-S, S(O)R3b, S(O)2R3a, S(O)2NR2R2a, and OCF3; Râ€² is selected from H, F, Cl, Br, I, SR3, CO2R3, NO2, (CH2)tOR3, C1-4 alkyl, OCF3, CF3, C(O)NR7R8, and (CR8R9)tNR7R8; M is attached to ring E and is selected from the group: Ja is NH or NR1a; Z is selected from a bond, C1-4 alkylene, (CH2)rO(CH2)r, (CH2)rNR3(CH2)r, (CH2)rC(O)(CH2)r, (CH2)rC(O)O(CH2)r, (CH2)rOC(O)(CH2)r, (CH2)rC(O)NR3(CH2)r, (CH2)rNR3C(O)(CH2)r, (CH2)rOC(O)O(CH2)r, (CH2)rOC(O)NR3(CH2)r, (CH2)rNR3C(O)O(CH2)r, (CH2)rNR3C(O)NR3(CH2)r, (CH2)rS(O)p(CH2)r, (CH2)rSO2NR3(CH2)r, (CH2)rNR3SO2(CH2)r, and (CH2)rNR3SO2NR3(CH2)r, provided that Z does not form a Nâ€”N, Nâ€”O, Nâ€”S, NCH2N, NCH2O, or NCH2S bond with ring M or group A; R1a and R1b are independently absent or selected from â€”(CH2)râ€”R1â€², â€”CH&boxH;CHâ€”R1â€², NCH2R1â€³, OCH2R1â€³, SCH2R1â€³, NH(CH2)2(CH2)tR1â€², O(CH2)2(CH2)tR1â€², and S(CH2)2(CH2)tR1â€²; alternatively, R1a and R1b, when attached to adjacent carbon atoms, together with the atoms to which they are attached form a 5-8 membered saturated, partially saturated or unsaturated ring substituted with 0-2 R4 and which contains from 0-2 heteroatoms selected from the group consisting of N, O, and S; alternatively, when Z is C(O)NH and R1a is attached to a ring carbon adjacent to Z, then R1a is a C(O) bound to Z by replacing the amide hydrogen of Z to form a cyclic imide; R1â€² is selected from H, C1-3 alkyl, F, Cl, Br, I, â€”CN, â€”CHO, (CF2)rCF3, (CH2)rOR2, NR2R2a, C(O)R2c, OC(O)R2, (CF2)rCO2R2c, S(O)pR2b, NR2(CH2)rOR2, CH(&boxH;NR2c)NR2R2a, NR2C(O)R2b, NR2C(O)NHR2b, NR2C(O)2R2a, OC(O)NR2aR2b, C(O)NR2R2a, C(O)NR2(CH2)rOR2, SO2NR2R2a, NR2SO2R2b, C3-6 carbocyclic residue substituted with 0-2 R4a, and 5-10 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R4a; R1â€³ is selected from H, CH(CH2OR2)2, C(O)R2c, C(O)NR2R2a, S(O)R2b, S(O)2R2b, and SO2NR2R2a; R2, at each occurrence, is selected from H, CF3, C1-6 alkyl, benzyl, C3-6 carbocyclic residue substituted with 0-2 R4b, and 5-6 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R4b; R2a, at each occurrence, is selected from H, CF3, C1-6 alkyl, benzyl, phenethyl, C3-6 carbocyclic residue substituted with 0-2 R4b, and 5-6 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R4b; R2b, at each occurrence, is selected from CF3, C1-4 alkoxy, C1-6 alkyl, benzyl, C3-6 carbocyclic residue substituted with 0-2 R4b, and 5-6 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R4b; R2c, at each occurrence, is selected from CF3, OH, C1-4 alkoxy, C1-6 alkyl, benzyl, C3-6 carbocyclic residue substituted with 0-2 R4b, and 5-6 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R4b; alternatively, R2 and R2a, together with the atom to which they are attached, combine to form a 5 or 6 membered saturated, partially saturated or unsaturated ring substituted with 0-2 R4b and containing from 0-1 additional heteroatoms selected from the group consisting of N, O, and S; R3, at each occurrence, is selected from H, C1-4 alkyl, and phenyl; R3a, at each occurrence, is selected from H, C1-4 alkyl, and phenyl; R3b, at each occurrence, is selected from H, C1-4 alkyl, and phenyl; R3c, at each occurrence, is selected from C1-4 alkyl, and phenyl; R3d, at each occurrence, is selected from H, OH, and C1-3 alkyl; R3e, at each occurrence, is selected from H and CH3; A is a C3-10 carbocyclic residue substituted with 0-2 R4; Xâ€”Y combine to form NR4cC(R3dR3e); R4, at each occurrence, is selected from H, &boxH;O, (CH2)rOR2, F, Cl, Br, I, C1-4 alkyl, â€”CN, NO2, (CH2)rNR2R2a, (CH2)rC(O)R2c, NR2C(O)R2b, C(O)NR2R2a, NR2C(O)NR2R2a, CH(&boxH;NR2)NR2R2a, CH(&boxH;NS(O)2R5)NR2R2a, NHC(&boxH;NR2)NR2R2a, C(O)NHC(&boxH;NR2)NR2R2a, SO2NR2R2a, NR2SO2NR2R2a, NR2SO2â€”C1-4 alkyl, NR2SO2R5, S(O)pR5, (CF2)rCF3, NCH2R1â€³, OCH2R1â€³, SCH2R1â€³, N(CH2)2(CH2)tR1â€², O(CH2)2(CH2)tRâ€², and S(CH2)2(CH2)tR1â€²; alternatively, one R4 is a 5-6 membered aromatic heterocycle containing from 1-4 heteroatoms selected from the group consisting of N, O, and S; R4a is selected from H, &boxH;O,(CH2)rOR2, (CH2)râ€”F, (CH2)râ€”Br, (CH2)râ€”Cl, I, C1-4 alkyl, â€”CN, NO2, (CH2)rNR2R2a, (CH2)rNR2R2b, (CH2)rC(O)R2c, NR2C(O)R2b, C(O)NR2R2a, C(O)NH(CH2)2NR2R2a, NR2C(O)NR2R2a, CH(&boxH;NR2)NR2R2a, NHC(&boxH;NR2)NR2R2a, SO2NR2R2a, NR2SO2NR2R2a, NR2SO2â€”C1-4 alkyl, C(O)NHSO2â€”C1-4 alkyl, NR2SO2R5, S(O)pR5, and (CF2)rCF3; R4b, at each occurrence, is selected from H, &boxH;O, (CH2)rOR3, F, Cl, Br, I, C1-4 alkyl, â€”CN, NO2, (CH2)rNR3R3a, (CH2)rC(O)R3, (CH2)rC(O)OR3c, NR3C(O)R3a, C(O)NR3R3a, NR3C(O)NR3R3a, CH(&boxH;NR3)NR3R3a, NH3C(&boxH;NR3)NR3R3a, SO2NR3R3a, NR3SO2NR3R3a, NR3SO2â€”C1-4 alkyl, NR3SO2CF3, NR3SO2-phenyl, S(O)pCF3, S(O)pâ€”C1-4 alkyl, S(O)p-phenyl, and (CF2)rCF3; R4c, at each occurrence, is selected from H, C1-4 alkyl, CH2â€”CN, (CH2)2â€”CN, CH2â€”NR2R2a, (CH2)2NR2R2a, CH2C(O)R2c, (CH2)2C(O)R2c, CH2â€”C(O)NR2R2a, (CH2)2C(O)NR2R2a, phenyl, and benzyl; R5, at each occurrence, is selected from CF3, C1-6 alkyl, phenyl substituted with 0-2 R6, and benzyl substituted with 0-2 R6; R6, at each occurrence, is selected from H, OH, (CH2)rOR2, F, Cl, Br, I, C1-4 alkyl, CN, NO2, (CH2)rNR2R2a, (CH2)rC(O)R2b, NR2C(O)R2b, NR2C(O)NR2R2a, CH(&boxH;NH)NH2, NHC(&boxH;NH)NH2, SO2NR2R2a, NR2SO2NR2R2a, and NR2SO2C1-4 alkyl; R7, at each occurrence, is selected from H, OH, C1-6 alkyl, C1-6 alkylcarbonyl, C1-6 alkoxy, C1-4 alkoxycarbonyl, (CH2)n-phenyl, C6-10 aryloxy, C6-10 aryloxycarbonyl, C6-10 arylmethylcarbonyl, C1-4 alkylcarbonyloxy C1-4 alkoxycarbonyl, C6-10 arylcarbonyloxy C1-4 alkoxycarbonyl, C1-6 alkylaminocarbonyl, phenylaminocarbonyl, and phenyl C1-4 alkoxycarbonyl; R8, at each occurrence, is selected from H, C1-6 alkyl and (CH2)n-phenyl; alternatively, R7 and R8 combine to form a 5 or 6 membered saturated, ring which contains from 0-1 additional heteroatoms selected from the group consisting of N, O, and S; R9, at each occurrence, is selected from H, C1-6 alkyl and (CH2)n-phenyl; n is selected from 0, 1, 2, and 3; m is selected from 0, 1, and 2; p is selected from 0, 1, and 2; r is selected from 0, 1, 2, and 3; s is selected from 0, 1, and 2; and, t is selected from 0 and 1.