Patent ID: 6548525
Filing Date: 2003-04-15
Classification: C07D

Abstract:
A compound of formula I: or a stereoisomer or pharmaceutically acceptable salt thereof, wherein;ring M contains, in addition to J, 2 N atoms and R1b is not present; J is N or NH; D is selected from CN, C(&boxH;NR8)NR7R9, NHC(&boxH;NR8)NR7R9, NR8CH(&boxH;NR7), C(O)NR7R8, and (CR8R9)tNR7R8, provided that D is substituted ortho to G on E; E is selected from phenyl, pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, and piperidinyl substituted with 1-2 R; R is selected from H, Cl, F, Br, I, (CH2)tOR3, C1-4 alkyl, OCF3, CF3, C(O)NR7R8, and (CR8R9)tNR7R8; G is absent or is selected from NHCH2, OCH2, and SCH2, provided that when s is 0, then G is attached to a carbon atom on ring M; Z is selected from a 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; 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, C(&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 R4, 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 R4; 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, 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 combine to form a 5 or 6 membered saturated, partially saturated or unsaturated ring substituted with 0-2 R4b which contains from 0-1 additional heteroatoms selected from the group consisting of N, O, and S; 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; R3c, at each occurrence, is selected from C1-4 alkyl, and phenyl; A is selected from: C3-10 carbocyclic residue substituted with 0-2 R4, 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 R4; B is selected from: Y, Xâ€”Y, NR2R2a, C(&boxH;NR2)NR2R2a, NR2C(&boxH;NR2)NR2R2a, C3-10 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; X is selected from C1-4 alkylene, â€”CR2(CR2R2b) (CH2)tâ€”, â€”C(O)â€”, â€”C(&boxH;NR1â€³)â€”, â€”CR2(NR1â€³R2)â€”, â€”CR2(OR2)â€”, â€”CR2(SR2)â€”, â€”C(O)CR2R2aâ€”, â€”CR2R2aC(O), â€”S(O)pâ€”, â€”S(O)pCR2R2aâ€”, â€”CR2R2aS(O)pâ€”, â€”S(O)2NR2â€”, â€”NR2S (O)2â€”, â€”NR2S(O)2CR2R2aâ€”, â€”CR2R2aS(O)2NR2â€”, â€”NR2S(O)2NR2â€”, â€”C(O)NR2â€”, â€”NR2C(O)â€”, â€”C(O)NR2CR2R2aâ€”, â€”NR2C(O)CR2R2aâ€”, â€”CR2R2aC(O)NR2â€”, â€”CR2R2aNR2C(O)â€”, â€”NR2C(O)Oâ€”, â€”OC(O)NR2â€”, â€”NR2C(O)NR2â€”, â€”NR2â€”, â€”NR2CR2R2aâ€”, â€”CR2R2aNR2â€”, O, â€”CR2R2aOâ€”, and â€”OCR2R2aâ€”; Y is selected from: (CH2)rNR2R2a, provided that Xâ€”Y do not form a Nâ€”N, Oâ€”N, or Sâ€”N bond, C3-10 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; 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, C(&boxH;NR2)NR2R2a, C(&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)tR1â€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, at each occurrence, is selected from H, &boxH;O, (CH2)rOR2, (CH2)râ€”F, (CH2)râ€”Br, (CH2)râ€”Cl, Cl, Br, F, I, C1-4 alkyl, â€”CN, NO2, (CH2)rNR2R2a, (CH2)rC(O)R2c, NR2C(O)R2b, C(O)NR2R2a, C(O)NH(CH2)2NR2R2a, NR2C(O)NR2R2a, C(&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; alternatively, one R4a is a 5-6 membered aromatic heterocycle containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-1 R5; 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, C(&boxH;NR3)NR3R3a, NR3C(&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; 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, halo, C1-4 alkyl, CN, NO2, (CH2)rNR2R2a, (CH2)rC(O)R2b, NR2C(O)R2b, NR2C(O)NR2R2a, C(&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, at each occurrence, is selected from 0, 1, 2, and 3; p, at each occurrence, is selected from 0, 1, and 2; r, at each occurrence, is selected from 0, 1, 2, and 3; s, at each occurrence, is selected from 0, 1, and 2; and, t, at each occurrence, is selected from 0, 1, 2, and 3; provided that Dâ€”Eâ€”Gâ€”(CH2)sâ€” and â€”Zâ€”Aâ€”B are not both benzamidines.