Patent ID: 6599926
Filing Date: 2003-07-29
Classification: A61P,C07D

Abstract:
A compound of formula Ib2: or a stereoisomer or pharmaceutically acceptable salt thereof, wherein;ring D2 is a 5-membered heteroaromatic ring comprising E, carbon atoms, and 0-3 N atoms, wherein F is selected from O, S, and Nâ€”Rc and ring D2 is substituted with 1 Ra and 0-1 Rb; R is selected from H, C1-4 alkyl, F, Cl, Br, I, OH, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, CN, C(&boxH;NR8) NR7R9, NHC(&boxH;NR8)NR7R9, NR8CH(&boxH;NR7), NH2, NH(C1-3 alkyl), N(C1-3 alkyl)2, C(&boxH;NH)NH2, CH2NH2, CH2NH(C1-3 alkyl), CH2N(C1-3 alkyl)2, CH2CH2NH2, CH2CH2NH(C1-3 alkyl), CH2CH2N(C1-3 alkyl)2, (CR8R9)tNR7R8, (CR8R9)tC(O)NR7R8, and OCF3; Ra is selected from H, C1-4 alkyl, F, Cl, Br, I, OH, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, ON, C(&boxH;NR8)NR7R9, NHC(&boxH;NR8)NR7R9, NR8CH(&boxH;NR7), NH2, NH(C1-3 alkyl), N(C1-3 alkyl)2, C(&boxH;NH)NH2, CH2NH2, CH2NH(C1-3 alkyl), CH2N(C1-3 alkyl)2, CH2CH2NH2, CH2CH2NH(C1-3 alkyl), CH2CH2N(C1-3 alkyl)2, (CR8R9)tNR7R8, (CR8R9)tC(O)NR7R8, and OCF3; Rb is selected from H, C1-4 alkyl, F, Cl, Br, I, OH, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, ON, C(&boxH;NR8)NR7R9, NHC(&boxH;NR8)NR7R9, NR8CH(&boxH;NR7), NH2, NH(C1-3 alkyl), N(C1-3 alkyl)2, C(&boxH;NH)NH2, CH2NH2, CH2NH(C1-3 alkyl), CH2N(C1-3 alkyl)2, CH2CH2NH2, CH2CH2NH(C1-3 alkyl), CH2CH2N(C1-3 alkyl)2, (CR8R9)tNR7R8, (CR8R9)tC(O)NR7R8, and OCF3; Rc is selected from H, C1-4 alkyl, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, NH2, NH(C1-3 alkyl), N(C1-3 alkyl)2, C(&boxH;NH)NH2, CH2NH2, CH2NH(C1-3 alkyl), CH2N(C1-3 alkyl)2, CH2CH2NH2, CH2CH2NH(C1-3 alkyl), CH2CH2N(C1-3 alkyl)2, (CR8R9)tNR7R8, (CR8R9)tC(O)NR7R8, and OCF3; M is isoxazoline, pyrazoline, isothiazoline, triazoline, tetrazoline, phenyl, or a 5-6 membered aromatic heterocycle consisting of carbon atoms and 1-4 heteroatoms selected from O, N, and S, and is substituted with -Z-A-B; M is also substituted with 0-2 R1a; Z is selected from a bond, â€”(CR2R2a)1-4â€”, (CR2R2a)qO(CR2R2a)q1, (CR2R2a)qNR3(CR2R2a)q1, (CR2R2a)qC(O)(CR2R2a)q1, (CR2R2a)qC(O)O(CR2R2a)q1, (CR2R2a)qOC(O)(CR2R2a)q1, (CR2R2a)qC(O)NR3(CR2R2a)q1, (CR2R2a)qNR3C(O)(CR2R2a)q1, (CR2R2a)qOC(O)O(CR2R2a)q1, (CR2R2a)qOC(O)NR3(CR2R2a)q1, (CR2R2a)qNR3C(O)O(CR2R2a)q1, (CR2R2a)qNR3C(O)NR3(CR2R2a)q1, (CR2R2a)qS(CR2R2a)q1, (CR2R2a)qS(O)(CR2R2a)q1, (CR2R2a)qS(O)2(CR2R2a)q1, (CR2R2a)qSO2NR3(CR2R2a)q1, (CR2R2a)qNR3SO2(CR2R2a)q1, and (CR2R2a)qNR3SO2NR3(CR2R2a)q1, wherein q+q1 total 0, 1, or 2, provided that Z does not form a Nâ€”N, Nâ€”O, Nâ€”S, NCH2N, NCH2O, or NCH2S bond with either group to which it is attached; R1a is selected from H, â€”(CH2)râ€”R1b, â€”CH&boxH;CHâ€”R1b, NCH2R1c, OCH2R1c, SCH2R1c, NH(CH2)2(CH2)tR1b, O(CH2)2(CH2)tR1b, S(CH2)2(CH2)tR1b, S(O)p(CH2)rR1b, O(CH2)rR1d, NR3(CH2)rR1b, OC(O)NR3(CH2)rR1d, NR3C(O)NR3(CH2)rR1d, NR3C(O)O(CH2)rR1d, and NR3C(O)(CH2)rR1d, provided that R1a forms other than an N-halo, Nâ€”N, Nâ€”S, Nâ€”O, or Nâ€”CN bond; alternatively, when two R1a's are attached to adjacent atoms, together with the atoms to which they are attached they form a 5-7 membered ring consisting of: carbon atoms and 0-2 heteroatoms selected from the group consisting of N, O, and S(O)p, this ring being substituted with 0-2 R4b and comprising: 0-3 double bonds; R1b 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)rCO2R2a, 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 carbocycle substituted with 0-2 R4a, and 5-10 membered heterocycle consisting of carbon atoms and from 1-4 heteroatoms selected from the group consisting of N, O, and S(O)p substituted with 0-2 R4a, provided that R1b forms other than an N-halo, Nâ€”N, Nâ€”S, Nâ€”O, or Nâ€”CN bond; R1c is selected from H, CH(CH2OR2)2, C(O)R2c, C(O)NR2R2a, S(O)R2b, S(O)2R2b, and SO2NR2R2a; R1d is selected from C3-13 carbocycle substituted with 0-2 R4a, and 5-13 membered heterocycle consisting of carbon atoms and from 1-4 heteroatoms selected from the group consisting of N, O, and S(O)p substituted with 0-2 R4a, provided that R1d forms other than an Nâ€”N, Nâ€”S, or Nâ€”O bond; R2, at each occurrence, is selected from H, CF3, C1-6 alkyl, benzyl, C3-6 carbocycle substituted with 0-2 R4b, and 5-6 membered heterocycle comprising carbon atoms and 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 carbocycle substituted with 0-2 R4b, and 5-6 membered heterocycle comprising carbon atoms and 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 carbocycle substituted with 0-2 R4b, and 5-6 membered heterocycle comprising carbon atoms and 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 carbocycle substituted with 0-2 R4b, and 5-6 membered heterocycle comprising carbon atoms and 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 comprising carbon atoms and 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, C1-4 alkyl, C1-4 alkyl-phenyl, and C(&boxH;O)R3c; A is selected from: C3-10 carbocycle substituted with 0-2 R4, and 5-12 membered heterocycle comprising carbon atoms and from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R4; B is selected from: H, Y, and X-Y, provided that Z and B are attached to different atoms on A; X is selected from â€”(CR2R2a)1-4, â€”CR2(CR2R2b)(CH2)tâ€”, â€”C(O)â€”, â€”C(&boxH;NR1c)â€”, â€”CR2(NR1cR2)â€”, â€”CR2(OR2)â€”, â€”CR2(SR2)â€”, â€”S(O)CR2R2aâ€”, â€”S(O)2CR2R2aâ€”, â€”CR2R2aSâ€”, â€”CR2R2aS(O)â€”, â€”CR2R2aS(O)2â€”, 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€”, CR2R2aNR2â€”, O, â€”CR2R2aOâ€”, and â€”OCR2R2aâ€”; Y is selected from: C3-10 carbocycle substituted with 0-2 R4a, and 5-12 membered heterocycle comprising carbon atoms and 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, (CH2)rF, (CH2)rCl, (CH2)rBr, (CH2)rI, C1-4 alkyl, (CH2)rCN, (CH2)rNO2, (CH2)rNR2R2a, C(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, (CH2)râˆ’CF3, NCH2R1c, OCH2R1c, SCH2R1c, N(CH2)2(CH2)tR1b, O(CH2)2(CH2)tR1b, S(CH2)2(CH2)tR1b, 5-6 membered carbocycle substituted with 0-1 R5, and 5-6 membered heterocycle consisting of: carbon atoms and 1-4 heteroatoms selected from the group consisting of N, O, and S(O)p substituted with 0-1 R5; R4a, at each occurrence, is selected from H, &boxH;O, (CH2)rOR2, (CF2)rCF3, (CH2)râ€”CF3, (CH2)râ€”F, (CH2)râ€”Br, (CH2)râ€”Cl, C1-4 alkyl, (CH2)rCN, (CH2)rNO2, (CH2)rNR2R2a, (CH2)rC(O)R2c, NR2C(O)R2b, C(O)NR2R2a, (CH2)rN&boxH;CHOR3, C(O)NH(CH2)2NR2R2a, NR2C(O)NR2R2a, C(&boxH;NR2)NR2R2a, NHC(&boxH;NR2)NR2R2a, SO2NR2R2a, NR2SO2NR2R2a, NR2SO2â€”C1-4 alkyl, NR2SO2R5, C(O)NHSO2â€”C1-4 alkyl, S(O)pR5, 5-6 membered carbocycle substituted with 0-1 R5, and 5-6 membered heterocycle consisting of: carbon atoms and 1-4 heteroatoms selected from the group consisting of N, O, and S(O)p substituted with 0-1 R5; R4b, at each occurrence, is selected from H, &boxH;O, (CH2)rOR3, (CH2)râ€”F, (CH2)râ€”Cl, (CH2)râ€”Br, (CH2)râ€”I, C1-4 alkyl, (CH2)râ€”CN, (CH2)râ€”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, (CH2)rCF3, and (CF2)rCF3; R5, at each occurrence, is selected from H, C1-6 alkyl, &boxH;O, (CH2)rOR3, F, Cl, Br, I, â€”CN, NO2, (CH2)rNR3R3a, (CH2)rC(O)R3, (CH2)rC(O)OR3c, NR3C(O)R3a, C(O)NR3R3a, NR3C(O)NR3R3a, CR(&boxH;NOR3d), 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, (CF2)rCF3, phenyl substituted with 0-2 R6, naphthyl 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, C1-4 alkoxycarbonyl, 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, when attached to the same nitrogen, combine to form a 5-6 membered heterocyclic ring consisting of carbon atoms and 0-2 additional heteroatoms selected from the group consisting of N, O, and S(O)p; 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; m, at each occurrence, is selected from 0, 1, and 2; 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.