Substituted tetrahydroisoquinoline compounds as factor XIa inhibitors

A compound according to formula (I):

• or a stereoisomer, tautomer, pharmaceutically acceptable salt thereof, wherein:
• ring A is C3-6 carbocycle;
• ring B is 4- to 7-membered heterocycle containing carbon atoms and 0-3 additional heteroatoms selected from the group consisting of N, NR6, O, and S(O)p;
• optionally, ring B forms a fused ring or Spiro ring with a 4- to 7-membered heterocycle containing carbon atoms and 1-3 heteroatoms selected from the group consisting of NR6, O, and S(O)p;
• ring B, including the fused ring or Spiro ring is substituted with 1-3 R5;
• L is selected from the group consisting of:
• —CHR10CHR10—, —C≡C—, —CHR10NH—, —NHCHR10—, —SCH2—, —CH2S—, —SO2CH2—, −CH2SO2—, —NHCH2—, and —CH2NH—;
• R1, at each occurrence, is selected from the group consisting of H, halo, C1-6 alkyl, C1-4 alkoxy, C1-4 alkylthio, OH, SH, CHF2, CF3, OCF3, CN, NH2, COC1-4 alkyl, CO2(C1-4 alkyl), —CH2CO2H, —CH2CO2(C1-4 alkyl), —CH2NH2, —CONH2, —CONH(C1-4 alkyl), —NHCO(C1-4 alkyl), —NHCO2(C1-4 alkyl), —NHSO2(C1-4 alkyl), and —SO2NH2, and —C(═NH)NH2;
• R2 is selected from the group consisting of:
• H, halo, CN, OH, C1-6 alkyl, C1-4 alkoxy, C1-6haloalkyl, C1-6haloalkoxy, CO(C1-4 alkyl), CONH2, CO2H, CH2NH2, and a 5- to 7-membered heterocycle comprising carbon atoms and 1-4 heteroatoms selected from N, NRc, O, and S(O)p, wherein said heterocycle is substituted with 0-2 R2a;
• R2a, at each occurrence, is selected from the group consisting of:
• H, halo, C1-4 alkyl, —CH2OH, C1-4 alkoxy, OH, CF3, OCF3, CN, NH2, CO2H, CO2(C1-4 alkyl), CO(C1-4 alkyl), —CONH2, —CH2OH, —CH2OC1-4alkyl, —CH2NH2—, CONH(C1-4 alkyl), —CON(C1-4 alkyl)2, —SO2(C1-4 alkyl), —SO2NH2, —SO2NH(C1-4 alkyl), and —SO2N(C1-4 alkyl)2;
• R3 is selected from the group consisting of:
• C1-6 alkyl substituted with 1-3 R3a, —(CH2)n—C3-10 carbocycle substituted with 0-3 R3a or —(CH2)n-5-10 membered heterocycle containing carbon atoms and 1-4 heteroatoms selected from the group consisting of N, NR7, O, and S(O)p;
• wherein said heterocycle is substituted with 0-3 R3a;
• R3a, at each occurrence, is selected from the group consisting of:
• ═O, halo, C1-4 alkyl, OH, C1-4 alkoxy, CN, NH2, CO2H, CO2(C1-4 alkyl), CONH2, CONH(C1-6 alkyl), CON(C1-4 alkyl)2, —CONH—C1-4 alkylene-CO2(C1-4 alkyl), —CONHCO2C1-4 alkyl, —CONH—C1-4 alkylene-NHCO(C1-4 alkyl), —CONH—C1-4 alkylene-CONH2, —NHCOC1-4 alkyl, —NHCO2(C1-4 alkyl), —C1-4 alkylene-NHCO2C1-4 alkyl, Rf, CONHRf, and —CO2Rf;
• R4, at each occurrence, is selected from the group consisting of:
• H, halo and C1-4 alkyl;
• R5, at each occurrence, is selected from the group consisting of:
• H, ═O, halo, C1-4 alkyl, OH, CN, NH2, —N(C1-4 alkyl)2, NO2, C1-4 alkoxy, —OCO(C1-4 alkyl), —O—C1-4 alkylene-O(C1-4 alkyl), —O—C1-4 alkylene-N(C1-4 alkyl)2, —CO2H, —CO2(C1-4 alkyl), —CONH2, —(CH2)2CONH2, —CONR9(C1-4 alkyl), —CONR9—C1-4 alkylene-O(C1-4 alkyl), —CON(C1-4 alkyl)2, —CONR9—C1-4 alkylene-N(C1-4 alkyl)2, —CON(C1-4 alkyl)-C1-4 alkylene-O(C1-4 alkyl), —CONR9—C1-4 alkylene-CO2(C1-4 alkyl), —NR9COC1-4 alkyl, —NR9CO2C1-4 alkyl, —NR9CONH(C1-4 alkyl), —NR9CONR9—C1-4 alkylene-CO2C1-4 alkyl, —NR9—C1-4 alkylene-N(C1-4 alkyl)2, R8, —OR8, —O—C1-4 alkylene-R8, —COR8, —CO2R8, —CONR9R8, —NR9COR8, —NR9CO2R8, and —NR9CONR9R8;
• R6 is selected from the group consisting of:
• H, C1-4 alkyl, —CO2(C1-4 alkyl), —CO(C1-4 alkyl), —CONH2, —CO—C1-4 alkylene-N(C1-4 alkyl)2, —(CH2)2N(C1-4 alkyl)2, —CONR9(C1-4 alkyl), —CONR9—C1-4 alkylene-O(C1-4 alkyl), —CONR9—C1-4 alkylene-N(C1-4 alkyl)2, —CONR9—C1-4 alkylene-CO2(C1-4 alkyl), —CON(C1-4 alkyl)2, R8, —COR8, —CO2R8, and —CONR9R8;
• R7, at each occurrence, is selected from the group consisting of:
• H, C1-4 alkyl, COC1-4 alkyl, CO2(C1-4 alkyl), CO2Bn, —CONH—C1-4 alkylene-CO2C1-4 alkyl, phenyl, benzyl, and —CO2—C1-4 alkylene-aryl;
• R8, at each occurrence, is selected from the group consisting of:
• —(CH2)nC3-10 carbocycle substituted with 0-3 Re and —(CH2)n-5-10 membered heterocycle containing carbon atoms and 1-4 heteroatoms selected from the group consisting of N, NRd, O, and S(O)p;
• wherein said carbocycle and heterocycle are optionally substituted with ═O;
• R9, at each occurrence, is selected from the group consisting of:
• H and C1-4alkyl;
• R10, at each occurrence, is selected from the group consisting of:
• H, halo, OH, and C1-4 alkyl;
• Rc is, independently at each occurrence, selected from the group consisting of:
• H, C1-4 alkyl, COC1-4 alkyl, CO2C1-4 alkyl, and CO2Bn;
• Rd is, independently at each occurrence, selected from the group consisting of:
• H, C1-4 alkyl, CO(C1-4 alkyl), COCF3, CO2(C1-4 alkyl), —CONH—C1-4 alkylene-CO2C1-4 alkyl, CO2Bn, Rf, and CONHRf;
• Re is, independently at each occurrence, selected from the group consisting of:
• ═O, halo, C1-4 alkyl, C1-4 alkoxy, OCF3, NH2, NO2, N(C1-4 alkyl)2, CO(C1-4 alkyl), CO(C1-4 haloalkyl), CO2(C1-4 alkyl), CONH2, —CONH(C1-4 alkyl), —CONHPh, —CON(C1-4 alkyl)2, —CONH—C1-4 alkylene-O(C1-4 alkyl), —CONH—C1-4 alkylene-N(C1-4 alkyl)2, —CONH—C1-4 alkylene-CO2(C1-4 alkyl), —NHCO2(C1-4 alkyl), Rf, CORf, CO2Rf and CONHRf;
• Rf is, independently at each occurrence, selected from the group consisting of:
• —(CH2)n—C3-6 cycloalkyl, —(CH2)n-phenyl, and —(CH2)n-5- to 6-membered heterocycle containing carbon atoms and 1-4 heteroatoms selected from the group consisting of N, NRc, O, and S(O)p;
• wherein each ring moiety is substituted with 0-2 Rg;
• Rg is, independently at each occurrence, selected from the group consisting of:
• ═O, halo, C1-4 alkyl, OH, C1-4 alkoxy, and NHCO(C1-4 alkyl);
• n, at each occurrence, is selected from 0, 1, 2, 3, and 4;
• and
• p, at each occurrence, is selected from 0, 1, and 2.