Thrombin or factor Xa inhibitors

A compound selected from the group:

• or a stereoisomer or pharmaceutically acceptable salt thereof, wherein;
• G is selected from formulas Ia-Ic:
• ring D1 is selected from pyridine, pyrazine, pyridazine, and pyrimidine and is substituted with 1 D1a and 0-1 D1b;
• ring D2 is a 5-membered aromatic heterocycle comprising E, carbon atoms, and 0-3 N atoms, wherein E is selected from O, S and N-D1c and ring D2 is substituted with 1 D1a and 0-1 D1b;
• ring D3 is a 5-membered aromatic heterocycle comprising carbon atoms and from 0-3 additional N atoms and ring D3 is substituted with 1 D1a and 0-1 D1b;
• G1 is selected from H, C1-4 alkyl, F, Cl, Br, I, OH, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, CN, C (═NR8) NR7R9, NHC(═NR8)NR7R9, NR8CH(═NR7), NH2, NH(C1-3 alkyl), N(C1-3 alkyl)2, C(═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;
• D1a is selected from H, C1-4 alkyl, F, Cl, Br, I, OH, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, CN, C(═NR8) NR7R9, NHC(═NR8)NR7R9, NR8CH(═NR7), NH2, NH(C1-3 alkyl), N(C1-3 alkyl)2, C(═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;
• D1b is selected from H, C1-4 alkyl, F, Cl, Br, I, OH, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, CN, C (═NR8) NR7R9, NHC(═NR8)NR7R9, NR8CH(═NR7), NH2, NH(C1-3 alkyl), N(C1-3 alkyl)2, C(═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;
• D1c is selected from H, C1-4 alkyl, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, NH2, NH(C1-3 alkyl), N(C1-3 alkyl)2, C(═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)NR78, and OCH3;
• G2 is absent or is selected from CH2, C(O), O, NR3, S(O)p, CH2CH2, C(O)CH2, CH2C(O), OCH2, CH2O, NR3CH2, CH2NR3, S(O)pCH2, CH2S(O)p, CH2CH2CH2, C(O)CH2CH2, CH2C(O)CH2, CH2CH2C(O), OCH2CH2, CH2OCH2, CH2CH2O, NR3CH2CH2, CH2NR3CH2, CH2CH2NR3, S(O)pCH2CH2, CH2S(O)pCH2, and CH2CH2S(O)p;
• G3 is phenyl, naphthyl, or a 5-10 membered aromatic heterocycle consisting of carbon atoms and from 1-3 heteroatoms selected from N, O, and S;
• Ln is a linker which is absent or is selected from O, S, S(O)2, CH2, *NHC(O), *C(O)NH, *S(O)2NH, *NHS(O)2, *CH2NHC(O), *CH(Ra)NHC(O), *CH2NHC(O)CH2 and *CH(Ra)NHC(O)CH2, provided that Ln and M do not form an O—N or S—N bond and the * indicates where Ln is bonded to G;
• Ra is selected from C(O)C(O)OR3, C(O)C(O)NR2R2a, and C(O)-A;
• R is selected from H, Cl, F, Br, I, (CH2)tOR3, C1-4 alkyl, benzyl, OCF3, CF3, C(O)NR7R8, (CH2)tNR2SO2—C1-4 alkyl, and (CR8R9)tNR7R8;
• Z is selected from a (CR8R9)1-4, (CR8R9)rO(CR8R9)r, (CR8R9)rNR3(CR8R9)r, (CR8R9)rNR3C(CHR8) (CR8R9)r, (CR8R9)rC(O) (CR8R9)r, (CR8R9)rC(O)O(CR8R9)r, (CR8R9)rOC(O) (CR8R9)r, (CR8R9)rC(O)NR3(CR8R9)r, (CR8R9)rNR3C(O) (CR8R9)r, (CR8R9)rOC(O)O(CR8R9)r, (CH2)rOC(O)NR3(CR8R9)r, (CR8R9)rNR3C(O)O(CR8R9)r, (CH2)rNR3C(O)NR3(CR8R9)r, (CR8R9)rS(O)p(CR8R9)r, (CR8R9)rS(O)2 (CH═CH), (CCR8R9)rSO2NR3(CR8R9)r, (CR8R9) rNR3SO2 (CR8R9)r, and (CR8R9) rNR3SO2NR3(CR8R9)r, provided that Z does not form a N—N,N—O, N—S, NCH2N, NCH2O, or NCH2S bond with the groups to which Z is attached;
• R1b is selected from H, C1-3 alkyl, F, Cl, Br, I, —CN, —CHO, (CF2)rCF3, (CH2)rOR2, NR2R2a, C(O)R2c, OC(O)R2, (CF2)rCO2R2a, S(O)pR2b, NR2(CH2)rOR2, C(═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, N—N,N—S, N—O, or N—CN bond;
• R1c 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 carbocycle substituted with 0-2 R4b, and 5-6 membered heterocycle containing from 0-4 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 cycloalkylmethyl substituted with 0-2 R4b, C3-6 carbocycle substituted with 0-2 R4b, and 5-6 membered heterocycle 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 carbocycle substituted with 0-2 R4b, and 5-6 membered heterocycle 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 carbocycle substituted with 0-2 R4b, and 5-6 membered heterocycle 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, C1-4 alkyl, C1-4 alkyl-phenyl, and C(═O)R3c;
• A is selected from:
• C3-10 carbocycle substituted with 0-2 R4, and
• 5-12 membered heterocycle containing 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 —(CR2R2a)1-4—, —CR2(CR2R2b) (CH2)t—, —C(O)—, —C(═NR1c)—, —CR2(NR1cR2)—, —CR2(OR2)—, —CR2(SR2)—, —C(O)CR2R2a—, —CR2R2aC(O), —S—, —S(O)—, —S(O)2—, —SCR2R2a—, —S(O)CR2R2a—, —S(O)2CR2R2a—, —CR2R2aS—, —CR2R2aS(O)—, —CR2R2aS(O)2—, —S(O)2NR2—, —NR2S(O)2—, —NR2S(O)2CR2R2a—, —CR2R2aS(O)2NR2—, —NR2S(O)2NR2—, —C(O)NR2—, —NR2C(O)—, —C(O)NR2CR2R2a—, —NR2C(O)CR2R2a—, —CR2R2aC(O)NR2—, —CR2R2aNR2C(O)—, —NR2C(O)O—, —OC(O)NR2—, —NR2C(O)NR2—, —NR2—, —NR2CR2R2a—, —CR2R2aNR2—, O, —CR2R2aO—, and —OCR2R2a—;
• Y is selected from:
• C3-10 carbocycle substituted with 0-2 R4a, and
• 5-12 membered heterocycle containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R4a;
• alternatively, Z-A-B combine to form S—C1-6 alkyl;
• R4, at each occurrence, is selected from H, ═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(═NR2)NR2R2a, C(═NS(O)2R5)NR2R2a, NHC(═NR2)NR2R2a, C(O)NHC(═NR2)NR2R2a, SO2NR2R2a, NR2SO2NR2R2a, NR2SO2—C1-4 alkyl, NR2SO2R5, S(O)pR5, (CF2)rCF3, (CH2)r—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, ═O, (CH2)rOR2, (CF2)rCF3, (CH2)r—CF3, (CH2)r—F, (CH2)r—Br, (CH2)r—Cl, C1-4 alkyl, (CH2)rCN, (CH2)rNO2, (CH2)rNR2R2a, (CH2)rC(O)R2c, NR2C(O)R2b, C(O)NR2R2a, (CH2)rN═CHOR3, C(O)NH(CH2)2NR2R2a, NR2C(O)NR2R2a, C(═NR2)NR2R2a, NHC(═NR2)NR2R2a, SO2NR2R2a, NR2SO2NR2R2a, NR2SO2—C1-4 alkyl, NR2SO2R5, C(O)NHSO2—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, ═O, (CH2)rOR3, (CH2)r—F, (CH2)r—Cl, (CH2)r-Br, (CH2)r—I, C1-4 alkyl, (CH2)r—CN, (CH2)rNO2, (CH2)rNR3R3a, (CH2)rC(O)R3, (CH2)rC(O)OR3c, NR3C(O)R3a, C(O)NR3R3a, NR3C(O)NR3R3a, C (═NR3) NR3R3a, NR3C(═NR3) NR3R3a, SO2NR3R3a, NR3SO2NR3R3a, NR3SO2—C1-4 alkyl, NR3SO2CF3, NR3SO2-phenyl, S(O)pCF3, S(O)p—C1-4 alkyl, S(O)p-phenyl, (CH2)rCF3, and (CF2)rCF3;
• R5, at each occurrence, is selected from H, C1-6 alkyl, ═O, (CH2)rOR3, F, Cl, Br, I, —CN, NO2, (CH2)rNR3R3a, (CH2)rC(O)R3, (CH2)rC(O)OR3c, NR3C(O)R3a, C(O)NR3R3a, NR3C(O)NR3R3a, CH(═NOR3d), C(═NR3)NR3R3a, NR3C(═NR3)NR3R3a, SO2NR3R3a, NR3SO2NR3R3a, NR3SO2—C1-4 alkyl, NR3SO2CF3, NR3SO2-phenyl, S(O)pCF3, S(O)p-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(═NH)NH2, NHC(═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 heterocycle 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;
• p, at each occurrence, is selected from 0, 1, and 2;
• r, at each occurrence, is selected from 0, 1, 2, and 3;
• and,
• t, at each occurrence, is selected from 0, 1, 2, and 3.