Bridged ring compounds as hepatitis C virus (HCV) inhibitors and pharmaceutical applications thereof

A compound of Formula (I):

• or a stereoisomer, a geometric isomer, a tautomer, an N-oxide, a hydrate, a solvate, a pharmaceutically acceptable salt or a prodrug thereof,
• wherein each of A and A′ is independently a bond, alkyl, alkenyl, cycloalkyl, heterocycloalkyl, —(CR8R8a)n—O—(CR8R8a)p—, —(CR8R8a)n—N(R5)—(CR8R8a)p—, —(CR8R8a)n—S(═O)r—N(R5)—(CR8R8a)p—, —(CR8R8a)n—C(═O)—N(R5)—(CR8R8a)p—, —(CR8R8a)n—N(R5)—C(═O)—N(R5)—(CR8R8a)p—, —(CR8R8a)n—C(═O)—O—(CR8R8a)p—, —(CR8R8a)n—N(R5)—S(═O)r—N(R5)—(CR8R8a)p—, or —(CR8R8a)n—N(R5)—C(═O)—O—(CR8R8a)p—, or each of A and A′ is independently
• wherein each X1 is independently O, S, NR6, or CR7R7a;
• each X2 is independently NR6, O or S;
• each Y1 and Y2 is independently CR7;
• Z is —(CH2)a—, —CH═CH—, —N═CH—, —(CH2)a—N(R5)—(CH2)b—, or —(CH2)a—O—(CH2)b—, wherein
• each a and b is independently 0, 1, 2 or 3;
• each c is independently 1 or 2;
• each d is independently 1 or 2;
• each n is independently 0, 1, 2 or 3;
• each p is independently 0, 1, 2 or 3;
• each r is independently 0, 1 or 2;
• f is 0, 1, 2, 3 or 4;
• each of X and X′ is independently N;
• each of Y and Y′ is independently —C(═O)—(CR9R9a)n—N(R11)—C(═O)—O—R13 where n is selected from 1, 2, or 3;
• R1 and R2, together with X—CH they are attached to, form a 3-8 membered heterocycle, C5-12 fused heterobicycle or C5-12 spiro heterobicycle and R3 and R4, together with X′—CH they are attached to, form a 3-8 membered heterocycle, C5-12 fused heterobicycle or C5-12 spiro heterobicycle;
• each R5 is independently H, deuterium, hydroxy, alkyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, aralkyl, alkoxy, alkyl-OC(═O)—, alkyl-C(═O)—, carbamoyl, alkyl-OS(═O)r—, alkyl-S(═O)rO—, alkyl-S(═O)r— or aminosulfonyl;
• each R5a is independently H, deuterium, oxo (═O), hydroxy, amino, F, Cl, Br, I, cyano, R7aR7N—, —C(═O)NR7R7a, —OC(═O)NR7R7a, —OC(═O)OR7, —N(R7)C(═O)NR7R7a, —N(R7)C(═O)OR7a, —N(R7)C(═O)—R7a, R7R7aN—S(═O)2—, R7S(═O)2—, R7S(═O)2N(R7a)—, R7aR7N-alkyl, R7S(═O)-alkyl, R7R7aN—C(═O)-alkyl, R7aR7N-alkoxy, R7S(═O)-alkoxy, R7R7aN—C(═O)-alkoxy, aryl, heteroaryl, alkoxy, alkylamino, alkyl, haloalkyl, alkenyl, alkynyl, heterocyclyl, cycloalkyl, mercapto, nitro, aralkyl, arylamino, heteroarylamino, arylalkylamino, heteroarylalkylamino, heteroaryloxy, heteroarylalkyl, arylalkoxy, heteroarylalkoxy, heterocyclyloxy, heterocyclylalkoxy, heterocyclylamino, heterocyclylalkylamino or aryloxy;
• each R6 is independently H, deuterium, R7R7aNC(═O)—, R7OC(═O)—, R7C(═O)—, R7R7aNS(═O)—, R7OS(═O)—, R7S(═O)—, R7R7aNS(═O)2—, R7OS(═O)2—, R7S(═O)2—, aliphatic, haloaliphatic, hydroxyaliphatic, aminoaliphatic, alkoxyaliphatic, alkylaminoaliphatic, alkylthioaliphatic, arylaliphatic, heteroarylaliphatic, heterocyclylaliphatic, cycloalkylaliphatic, aryloxyaliphatic, heterocyclyloxyaliphatic, cycloalkyloxyaliphatic, arylaminoaliphatic, heterocyclylaminoaliphatic, cycloalkylaminoaliphatic, aryl, heteroaryl, heterocyclyl or carbocyclyl;
• each R6a is independently H, deuterium, hydroxy, amino, F, Cl, Br, I, cyano, oxo (═O), R7aR7N—, —C(═O)NR7R7a, —OC(═O)NR7R7a, —OC(═O)OR7, —N(R7)C(═O)NR7R7a, —N(R7)C(═O)OR7a, —N(R7)C(═O)—R7a, R7R7aN—S(═O)2—, R7S(═O)2—, R7S(═O)2N(R7a)—, R7aR7N-alkyl, R7S(═O)-alkyl, R7R7aN—C(═O)-alkyl, R7aR7N-alkoxy, R7S(═O)-alkoxy, R7R7aN—C(═O)-alkoxy, aryl, heteroaryl, alkoxy, alkylamino, alkyl, haloalkyl, alkenyl, alkynyl, heterocyclyl, cycloalkyl, mercapto, nitro, aralkyl, arylamino, heteroarylamino, arylalkylamino, heteroarylalkylamino, heteroaryloxy, heteroarylalkyl, arylalkoxy, heteroarylalkoxy, heterocyclyloxy, heterocyclylalkoxy, heterocyclylamino, heterocyclylalkylamino, or aryloxy;
• each R7 and R7a is independently H, deuterium, F, Cl, aliphatic, heteroalkyl, haloaliphatic, hydroxyaliphatic, aminoaliphatic, alkoxyaliphatic, alkylaminoaliphatic, alkylthioaliphatic, arylaliphatic, heterocyclylaliphatic, cycloalkylaliphatic, aryloxyaliphatic, heterocyclyloxyaliphatic, cycloalkyloxyaliphatic, arylaminoaliphatic, heterocyclylaminoaliphatic, cycloalkylaminoaliphatic, aryl, heteroaryl, heterocyclyl or carbocyclyl, with the proviso that where R7 and R7a are bonded to the same nitrogen atom, R7 and R7a, together with the nitrogen atom they are attached to, optionally form a substituted or unsubstituted 3-8 membered ring, or a substituted or unsubstituted spiro or fused bicyclic ring;
• each R8 and R8a is independently H, deuterium, hydroxy, cyano, nitro, F, Cl, Br, I, alkyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, aralkyl, alkoxy, alkyl-OC(═O)—, alkyl-C(═O)—, carbamoyl, alkyl-OS(═O)c—, alkyl-S(═O)cO—, alkyl-S(═O)c—, or aminosulfonyl;
• each R9, R9a, and R11 is independently H, deuterium, alkyl, cycloalkyl, aryl, or cycloalkylalkyl;
• each R13 and R13a is independently H, deuterium, alkyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, or aralkyl;
• wherein each of —(CR8R8a)n—O—(CR8R8a)p—, —(CR8R8a)n—N(R5)—(CR8R8a)p—, —(CR8R8a)n—S(═O)t—N(R5)—(CR8R8a)p—, —(CR8R8a)n—C(═O)—N(R5)—(CR8R8a)p—, —(CR8R8a)n—N(R5)—C(═O)—N(R5)—(CR8R8a)p—, —(CR8R8a)n—C(═O)—O—(CR8R8a)p—, —(CR8R8a)n—N(R5)—S(═O)r—N(R5)—(CR8R8a)p—, —(CR8R8a)n—N(R5)—C(═O)—O—(CR8R8a)p—, NR6, CR7R7a, CR7, —(CH2)a—, —CH═CH—, —N═CH—, —(CH2)a—N(R5)—(CH2)b—, —(CH2)a—O—(CH2)b—, R13aR13N—, —C(═O)R13, —C(═S)R13, —C(═O)—O—R13, —C(═O)NR13R13a, —OC(═O)NR13R13a, —OC(═O)OR13, —N(R13)C(═O)NR13R13a, —N(R13)C(═O)OR13a, —N(R13)C(═O)—R13a, R13R13aN—S(═O)2—, R13S(═O)2—, R13S(═O)2N(R13a)—, R13OS(═O)2—, R7aR7N—, —C(═O)NR7R7a, —OC(═O)NR7R7a, —OC(═)OR7, —N(R7)C(═O)NR7R7a, —N(R7)C(═O)OR7a, —N(R7)C(═O)—R7a, R7R7aN—S(═O)2—, R7S(═O)2—, R7S(═O)2N(R7a)—, alkyl-OC(═O)—, alkyl-C(═O)—, alkyl-OS(═O)c—, alkyl-S(═O)cO—, alkyl-S(═O)c—, R7R7aNC(═O)—, R7OC(═O)—, R7C(═O)—, R7R7aNS(═O)—, R7OS(═O)—, R7S(═O)—, R7R7aNS(═O)2—, R7OS(═O)2—, R7aR7N-alkyl, R7S(═O)-alkyl, R7R7aN—C(═O)-alkyl, R7aR7N-alkoxy, R7S(═O)-alkoxy, R7R7aN—C(═O)-alkylamino, alkyl, heteroalkyl, carbocyclyl, cycloalkyl, heterocyclyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, C5-12 fused bicycle, C5-12 fused heterobicycle, C5-12 spiro bicycle, C5-12 spiro heterobicycle, alkoxy, aliphatic, haloaliphatic, hydroxyaliphatic, aminoaliphatic, alkoxyaliphatic, alkylaminoaliphatic, alkylthioaliphatic, arylaliphatic, heteroarylaliphatic, heterocyclylaliphatic, cycloalkylaliphatic, aryloxyaliphatic, heterocyclyloxyaliphatic, cycloalkyloxyaliphatic, arylaminoaliphatic, heterocyclylaminoaliphatic, cycloalkylaminoaliphatic, haloalkyl, alkenyl, alkynyl, arylamino, heteroarylamino, arylalkylamino, heteroarylalkylamino, heteroaryloxy, heteroarylalkyl, arylalkoxy, heteroarylalkoxy, heterocyclyloxy, heterocyclylalkoxy, heterocyclylamino, heterocyclylalkylamino and aryloxy is optionally substituted with one or more substituents, wherein the substituent is deuterium, hydroxy, amino, halo, cyano, aryl, heteroaryl, alkoxy, alkylamino, alkylthio, alkyl, alkenyl, alkynyl, heterocyclyl, mercapto, nitro, aryloxy, heteroaryloxy, oxo (═O), carboxy, hydroxy-substituted alkoxy, hydroxy-substituted alkyl-C(═O)—, alkyl-C(═O)—, alkyl-S(═O)—, alkyl-S(═O)2—, hydroxy-substituted alkyl-S(═O)—, hydroxy-substituted alkyl-S(═O)2—, or carboxy-substituted alkoxy.