Pyrimidinones as factor xia inhibitors

A compound of Formula (I):

• or a stereoisomer, a tautomer, a pharmaceutically acceptable salt thereof, wherein:
• ring A is independently selected from 6-membered aryl and 5- to 6-membered heterocyclyl, wherein said aryl and heterocyclyl are optionally substituted with, where valence allows, one or more R4;
• ring B is 5- to 10-membered heterocyclyl optionally substituted with, where valence allows, one or more R3 or 5- to 10-membered heterocyclyl comprising carbon atoms and 1-4 heteroatoms selected from N, NR3c, O, and S(O)p and optionally substituted with, where valence allows, one or more R3;
• G1 is independently selected from C3-10 carbocyclyl and 5- to 10-membered heterocyclyl, wherein said carbocyclyl and heterocyclyl are optionally substituted with, where valence allows, one or more R8;
• X is independently selected from C4-8 alkylene and C4-8 alkenylene, wherein said alkylene and alkenylene are substituted with R1 and R2;
• alternatively one or more of the carbon atoms of said alkylene and alkenylene may be replaced by O, C═O, S(═O)p, S(═O)pNH, and NR5;
• Y is independently selected from —CR13NH—, —NHC(═O)—, —C(═O)NH—, —S(═O)pNH—, —NHS(═O)p—, and C1-2 alkylene;
• R1 and R2 are independently selected from H, D, halogen, haloalkyl, C1-6 alkyl (optionally substituted with R6), hydroxyl, and alkoxy optionally substituted with R6, and C3-6 cycloalkyl optionally substituted with R6;
• optionally, when R1 and R2 are attached to the same carbon atom, together they form an oxo group or C3-6 cycloalkyl;
• optionally, when R1 and R2 are attached to carbon atoms adjacent to each other, together they form a bond or carbocyclyl;
• optionally, R1 and R5 or R2 and R5 taken together form a ring;
• R3 is independently selected from H, NO2, ═O, halogen, haloalkyl, C1-4 alkyl (optionally substituted with R6), C2-4 alkenyl (optionally substituted with R6), C2-4 alkynyl (optionally substituted with R6), CN, —(CH2)n—OR5, —(CH2)n—NR5R5, —(CH2)n—C(═O)R5, —(CH2)n—C(═O)OR5, —(CH2)n—NR9C(═O)OR5, —(CH2)n—NR9C(═O)R5, —(CH2)n—NR9C(N—CN)NHR5, —(CH2)n—NR9C(NH)NHR5, —(CH2)n—N═CR9NR5R5, —(CH2)n—NR9C(═O)NR5R5, —(CH2)n—C(═O)NR5R5, —(CH2)n—NR9C(═S)NR9C(═O)R5, —(CH2)n—S(═O)pR5, —(CH2)n—S(═O)pNR5R5, —(CH2)n—NR9S(═O)pNR5R5, —(CH2)n—NR9S(═O)pR5, —(CH2)n—C3-10 carbocyclyl and —(CH2)n-4- to 10-membered heterocyclyl, wherein said carbocyclyl and heterocyclyl are optionally substituted with R6;
• optionally, two adjacent R3 groups on the heterocyclyl may form a ring optionally substituted with R6;
• R3c is independently selected from H, haloalkyl, C1-4 alkyl (optionally substituted with R6), —(CH2)1-2—OH, C(═O)C1-4 alkyl, —(CH2)0-2—C(═O)OH, —C(═O)OC1-4 alkyl, S(═O)pC1-6 alkyl, —(CH2)n—C3-10 carbocyclyl and —(CH2)n-4- to 10-membered heterocyclyl, wherein said carbocyclyl and heterocyclyl are optionally substituted with R6;
• R4 is independently selected from H, OH, NH2, halogen, CN, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy, —CH2OH, —C(═O)OH, —CH2C(═O)OH, —CO2(C1-4 alkyl), —C(═O)NH2, —C(═O)NH(C1-4 alkyl), —C(═O)N(C1-4 alkyl)2, —S(═O)2C1-4 alkyl, —S(═O)2NH2, C3-6 cycloalkyl, aryl, and 5- to 6-membered heterocyclyl, wherein said cycloalkyl, aryl and heterocyclyl are optionally substituted with R6;
• R5 is independently selected from H, C1-4 alkyl (optionally substituted with halogen, hydroxyl, alkoxy, carboxy, hydroxycarbonyl, alkoxycarbonyl, amino, substituted amino), —(CH2)n—C3-10 carbocyclyl and —(CH2)n-4- to 10-membered heterocyclyl, wherein said carbocyclyl and heterocyclyl are optionally substituted with R6;
• alternatively, R5 and R5 together with the nitrogen atom to which they are both attached form a heterocyclic ring optionally substituted with R6;
• R6 is independently selected from H, —(CH2)n—OH, ═O, —(CH2)nNH2, —(CH2)nCN, halogen, C1-6 alkyl, —(CH2)n—C(═O)OH, —(CH2)n—C(═O)NH2, —(CH2)n—C(═O)OC1-4 alkyl, —(CH2)n—OC1-4 alkyl, —(CH2)n—C3-10 carbocyclyl, —(CH2)n-4- to 10-membered heterocyclyl, and —O-4- to 10-membered heterocyclyl, wherein said carbocyclyl and heterocyclyl are optionally substituted with R10;
• R7 is independently selected from H, hydroxyl, alkoxy, halogen, amino, C1-3 haloalkyl, and C1-3 alkyl;
• R8 is independently selected from H, halogen, —(CH2)nCN, C1-6 alkyl, amino, aminoalkyl, haloalkyl, hydroxyl, alkoxy, haloalkoxy, alkylcarbonyl, carboxyl, carboxyl ester, amide, haloalkylaminocarbonyl, arylalkylaminocarbonyl, haloalkylaminocarbonyl, alkoxycarbonylamino, haloalkylcarbonylamino, arylamino, heteroarylamino, arylalkylcarbonyl, aryloxy, heteroaryloxy, alkylthio, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, sulfonamide, —(CH2)n-aryl, —(CH2)n—C3-6 cycloalkyl, and —(CH2)n-4- to 12-membered heterocyclyl, wherein said aryl, cycloalkyl, and heterocyclyl are optionally substituted with R10;
• alternatively, two adjacent R8 groups taken together form a heterocyclic ring optionally substituted with R10;
• R9 is H or C1-6 alkyl;
• R10 is independently selected from H, C1-6 alkyl (optionally substituted with R11), C2-6 alkenyl, C2-6 alkynyl, aryl (optionally substituted with R11), —(CH2)n—C3-6 cycloalkyl (optionally substituted with R11), —(CH2)n—O-4- to 10-membered heterocyclyl (optionally substituted with R11), halogen, —(CH2)nCN, NO2, ═O, C(═O)NR12R12, —(CH2)nC(═O)OR12, Si(C1-4 alkyl)3, —(CH2)n—OR12, —(CH2)n—NR12R12, —S(═O)pC1-6 alkyl, NR12S(═O)pC1-6 alkyl, S(═O)pNR12R12, and C(═NOH)NH2;
• R11, at each occurrence, is independently selected from H, halogen, C1-5 alkyl, —(CH2)n—OH, C3-6 cycloalkyl, phenyl, and heterocyclyl;
• R12, at each occurrence, is independently selected from H, C1-5 alkyl optionally substituted with R11, C3-6 cycloalkyl, phenyl, and heterocyclyl, or R12 and R12 together with the nitrogen atom to which they are both attached form a heterocyclic ring optionally substituted with C1-4 alkyl;
• R13 is, independently at each occurrence, selected from H, C1-4 haloalkyl, C1-4 alkyl, C(═O)OH, C(═O)O(C1-4 alkyl), C(═O)O(CH2)2O(C1-4 alkyl), C(═O)O(C1-4 haloalkyl), CH2C(═O)OH, CH2C(═O)O(C1-4 alkyl), C(═O)NH2, C(═O)NH(C1-4 alkyl), C(═O)N(C1-4 alkyl)2, and —C(═O)NH(C1-4 alkoxy);
• R15 is H or C1-6 alkyl;
• n, at each occurrence, is an integer independently selected from 0, 1, 2, 3, and 4;
• and
• p, at each occurrence, is an integer independently selected from 0, 1, and 2.