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 C3-10 carbocycle;
• L is selected from the group consisting of:
• a bond, —CHR10CHR10—, —CR10═CR10—, and —C≡C—;
• R1, at each occurrence, is selected from the group consisting of:
• H, halo, C1-2 alkyl, —O(C1-4 alkyl), CN, —CH2NH2, 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 and a 5- to 7-membered heterocycle comprising carbon atoms and 1-4 heteroatoms selected from N, NH, N(C1-4 alkyl), O, and S(O)p, wherein said heterocycle is substituted with 1-2 R2a;
• R2a, at each occurrence, is selected from the group consisting of:
• H, halo, C1-4 alkyl, CO2H, —CO2(C1-4 alkyl), —CONH2, —CH2OH, —CH2OC1-4alkyl, and —CH2NH2;
• R3 is selected from the group consisting of:
• C1-6 alkyl substituted with 1-3 R3a, C3-10 carbocycle substituted with 1-3 R3a, and 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 1-3 R3a;
• R3a, at each occurrence, is selected from the group consisting of:
• H, halo, C1-4 alkyl, —OH, C1-4 alkoxy, —CN, —NH2, —NH(C1-4 alkyl), —N(C1-4 alkyl)2, —CO2H, —CH2CO2H, —CO2(C1-4 alkyl), —CO2—C1-4 alkylene-O(C1-4 alkyl), —CO2—C1-4 alkylene-N(C1-4 alkyl)2, —CO2—C1-4 alkylene-O—C1-4 alkylene-N(C1-4 alkyl)2, —CO2—C1-4 alkylene-O—C1-4 alkylene-O(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), Rc, —CONHRc, and —CO2Rc;
• R4, at each occurrence, is selected from the group consisting of:
• H, halo, and C1-4 alkyl;
• R5 is selected from the group consisting of:
• halo, C1-4 alkyl substituted with 0-2 Rb, C2-4 alkenyl substituted with 0-2 Rb, —OH, —CN, —NH2, —N(C1-4 alkyl)2, —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), —CON(C1-4 alkyl)2, —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), —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, —NR9SO2(C1-4 alkyl), —S(C1-4 alkyl), —SO2(C1-4 alkyl), —SO2NH2, R8, C2-4 alkenylene-R8, —OR8, —COR8, C2-4 alkenylene-COR8, —CONR9R8, —NR9COR8, —NR9CO2R8, and —NR9CONR9R8;
• 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)n—C3-10 carbocycle and —(CH2)n-5- to 10-membered heterocycle containing carbon atoms and 1-4 heteroatoms selected from the group consisting of:
• N, NRa, O, and S(O)p;
• wherein said carbocycle or heterocycle is substituted with 0-3 Rb;
• 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;
• Ra is selected from the group consisting of:
• H, C1-4 alkyl, —(CH2)n—OH, CO(C1-4 alkyl), COCF3, CO2(C1-4 alkyl), —CONH2, —CONH—C1-4 alkylene-CO2(C1-4 alkyl), C1-4 alkylene-CO2(C1-4 alkyl), Rc, CO2Rc, and CONHRc;
• Rb is 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), —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-N′(C1-4 alkyl)2-C1-4 alkylene-O—P(O)(OH)2, —NHCO2(C1-4 alkyl), —Rc, CORc, CO2Rc, and CONHRc;
• Rc 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, NH, N(C1-4 alkyl), O, and S(O)p;
• wherein each ring moiety is substituted with 0-2 Rd;
• Rd is selected from the group consisting of:
• ═O, halo, —OH, C1-4 alkyl, NH2, NH(C1-4 alkyl), N(C1-4 alkyl)2, C1-4 alkoxy, and —NHCO(C1-4 alkyl), and heterocycle containing carbon atoms and 1-4 heteroatoms selected from the group consisting of:
• N, NH, N(C1-4 alkyl), O, and S(O)p;
• n, at each occurrence, is selected from 0, 1, 2, 3, and 4;
• p, at each occurrence, is selected from 0, 1, and 2;
• provided when R5 is heterocycle, the point of attachment of the heterocycle to the fused phenyl ring is not on a nitrogen atom.