Macrocycles as factor XIa inhibitors

A compound of Formula (Ia):

• or a pharmaceutically acceptable salt thereof, wherein:
• ring A is selected from aryl and a 5- to 6-membered heterocycle comprising:
• carbon atoms and 1-4 heteroatoms selected from N, NH, N(C1-4 alkyl), S(O)p, and O, wherein said aryl and heterocycle are optionally substituted with R1;
• ring B is a pyridazine optionally substituted with R10;
• ring C is a 4- to 6-membered heterocycle comprising:
• carbon atoms and 1-4 heteroatoms selected from N, NR9, S(O)p, and O, wherein said heterocycle is optionally substituted with R2;
• X is selected from C4-8 alkylene and C4-8 alkenylene, wherein said alkylene and alkenylene are substituted with R4 and R5;
• alternatively one or more of the carbon atoms of said alkylene and alkenylene may be replaced by O, C═O, S(O)p, NH, and N(C1-4 alkyl);
• Y is —CR6R7—NH—;
• R1 is selected from H, halogen, NO2, C1-6 alkyl, OH, haloalkyl, alkoxy, haloalkoxy, —C(═O)C1-3 alkyl, and CN;
• R2 is selected from H, ═O, OH, NH2, CF3, halogen, C1-4 alkyl (optionally substituted with OH), C1-3 alkoxy, and C(O)C1-3 alkyl;
• R3 is selected from H and C1-4 alkyl;
• alternatively, R2 and R3, together with the atoms to which they are directly or indirectly attached, form a ring;
• R4 and R5 are independently selected from H, halogen, C1-6 alkyl, OH, NH2, —CH2NH2, C1-4 haloalkyl, —OCH2F, —OCHF2, —OCF3, NH(C1-4 alkyl), N(C1-4 alkyl)2, C1-4 alkoxy, —CH2OH, and —CH2O(C1-4 alkyl);
• when R4 and R5 are not attached to the same carbon atom, they may be taken together with the carbon atoms to which they are attached to form a carbocycle;
• R6 is selected from H, halogen, C(O)OH, and C(O)O(C1-4 alkyl);
• R7 is selected from H, C1-4 alkyl, and CF3;
• alternatively, R6 and R7 together are ═O;
• R8 is, independently at each occurrence, selected from H, halogen, haloalkyl, CN, —(CH2)nOH, NR12R12, —CH2NH2, C(O)OH, —(CH2)n—NHC(O)OR12, —NHC(O)R12, —NHC(O)C(O)R12, —NHC(N—CN)NHR12, —NHC(NH)NHR12, —N═CHNR12R12, —NHC(O)NR12R12, —NHS(O)2C1-4 alkyl, —(CH2)n—CONR12R12, —(CH2)nC(O)O(C1-4 alkyl), —NHC(O)OCH2(C(CH2)2)O—(CH2)n—C3-10 carbocycle, —(CH2)n—C3-10 carbocycle, and —(CH2)n-4-10-membered heterocycle wherein said carbocycle and heterocycle are optionally substituted with R13;
• R9 is selected from H and C1-4 alkyl;
• R10 is selected from H, halogen, CN, ═O, OH, NH2, C3-6 cycloalkyl, C1-4 alkyl, C1-4 alkoxy, and C1-4 haloalkyl;
• R11 is selected from H, halogen, and methyl;
• R12 is selected from H, C1-4 alkyl (optionally substituted with halogen, hydroxy, alkoxy, carboxy, alkoxycarbonyl, and arylalkyloxy), —(CH2)n—C3-10 carbocycle and —(CH2)n-4-10-membered heterocycle, wherein said carbocycle and heterocycle are optionally substituted with R13;
• R13 is selected from OH, halogen, C1-6 alkyl, C3-6 cycloalkyl, —(CH2)n—C(═O)OH, —(CH2)n—C(═O)OC1-4 alkyl, —(CH2)n—OC1-4 alkyl, and =0;
• n is, independently at each occurrence, selected from 0, 1, 2, 3, and 4;
• p is, independently at each occurrence, selected from 0, 1, and 2.