Spiro ring compounds as hepatitis c virus (hcv) inhibitors

A compound of formula (I):

• or a stereoisomer, a geometric isomer, a tautomer, an N-oxide, a hydrate, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof, wherein
• each of A and A′ is independently a bond, alkylene, alkenylene, cycloalkylene, heterocyclylalkylene, —(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;
• X4 is (CR7R7a)n, —Y1═Y2—, O, S or NR6;
• W is carbocyclyl or heterocyclyl;
• each Y1 and Y2 is independently N or CR7;
• each Z is independently —(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 Q1 and Q2 is independently NR6, O, S, C(═O) or (CR7R7a)e;
• e is 0, 1, 2, 3 or 4;
• each of X and X′ is independently N or CR7;
• each of Y and Y′ is independently H, deuterium, alkyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, aralkyl, a group derived from α-amino acid or an optically isomer thereof;
• or each of Y and Y′ is independently —[U—(CR9R9a)t—N(R10)—(CR9R9a)t]k—U—(CR9R9a)t—N(R11)—(CR9R9a)t—R12, —U—(CR9R9a)t—R12 or —[U—(CR9R9a)t—N(R10)—(CR9R9a)t]k—U—(CR9R9a)t—O—(CR9R9a)t—R12;
• each U is independently —C(═O)—, —C(═S)—, —S(═O)— or —S(═O)2—;
• each t is independently 0, 1, 2, 3 or 4;
• each k is independently 0, 1 or 2;
• each of R1, R2, R3 and R4 is independently H, deuterium, alkyl, heteroalkyl, aralkyl, cycloalkyl, heterocyclyl, heteroaryl or aryl;
• or R1 and R2, together with X—CH they are attached to, optionally form a 3-8 membered heterocycle or carbocycle, C5-12 fused bicycle, C5-12 fused heterobicycle, C5-12 spiro bicycle or C5-12 spiro heterobicycle;
• or R3 and R4, together with X′—CH they are attached to, optionally form a 3-8 membered heterocycle or carbocycle, C5-12 fused bicycle, C5-12 fused heterobicycle, C5-12 spiro bicycle 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, R13aR13N—, —C(═O)NR13R13a, —OC(═O)NR13R13a, —OC(═O)OR13, —N(R13)C(═O)NR13R13a, —N(R13)C(═O)OR13, —N(R13)C(═O)—R13, R13R13aN—S(═O)2—, R13S(═O)2—, R13S(═O)2N(R13a)—, R13aR13N-alkyl, R13S(═O)-alkyl, R13R13aN—C(═O)-alkyl, R13aR13N-alkoxy, R13S(═O)-alkoxy, R13R13aN—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, R13R13aNC(═O)—, R13OC(═O)—, R13C(═O)—, R13R13aNS(═O)—, R13OS(—O)—, R13S(═O)—, R13R13aNS(═O)2—, R13OS(═O)2—, R13S(—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), R13aR13N—, —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)—, R13aR13N-alkyl, R13S(═O)-alkyl, R13R13aN—C(═O)-alkyl, R13aR13N-alkoxy, R13S(═O)-alkoxy, R13R13aN—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, Br, I, aliphatic, heteroalkyl, haloaliphatic, hydroxyaliphatic, aminoaliphatic, alkoxyaliphatic, alkylaminoaliphatic, alkylthioaliphatic, arylaliphatic, heteroarylaliphatic, heterocyclylaliphatic, cycloalkylaliphatic, aryloxyaliphatic, heterocyclyloxyaliphatic, cycloalkyloxyaliphatic, arylaminoaliphatic, heterocyclylaminoaliphatic, cycloalkylaminoaliphatic, aryl, heteroaryl, heterocyclyl or carbocyclyl;
• 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)r—, alkyl-S(═O)rO—, alkyl-S(═O)r— or aminosulfonyl;
• each R9, R9a, R10 and R11 is independently H, deuterium, alkyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, aralkyl, haloalkyl, hydroxyalkyl, heteroarylalkyl, heterocyclylalkyl or cycloalkylalkyl;
• each R12 is independently R13aR13N—, —C(═O)R13, —C(═S)R13, —C(═O)OR13, —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—, alkyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl or aralkyl;
• or R11 and R12 are optionally joined to form a 4-7 membered ring;
• and
• each R13 and R13a is independently H, deuterium, alkyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl or aralkyl;
• with the proviso that where R13 and R13a are bonded to the same nitrogen atom, R13 and R13a, 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;
• wherein each of alkylene, alkenylene, cycloalkylene, heterocyclylalkylene, —(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—, —(CR8R8a)n—N(R5)—C(═O)—O—(CR8R8a)p—, —[U—(CR9R9a)t—N(R10)—(CR9R9a)t]k—U—(CR9R9a)t—N(R11)—(CR9R9a)t—R12, —U—(CR9R9a)t—R12, —[U—(CR9R9a)t—N(R10)—(CR9R9a)t]k—U—(CR9R9a)t—O—(CR9R9a)t—R12, 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)OR13, —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—, alkyl-OC(═O)—, alkyl-C(═O)—, alkyl-OS(═O)r, alkyl-S(═O)rO—, alkyl-S(═O)r—, R13R13aNC(═O)—, R13OC(═O)—, R13C(═O)—, R13R13aNS(═O)—, R13OS(═O)—, R13S(═O)—, R13aR13N-alkyl, R13S(═O)-alkyl, R13R13aN—C(═O)-alkyl, R13aR13N-alkoxy, R13S(═O)-alkoxy, R13R13aN—C(═O)-alkylamino, alkyl, heteroalkyl, carbocyclyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, aralkyl, a group derived from α-amino acid, 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;
• or
• wherein W is C3-8 carbocyclyl or C2-10 heterocyclyl.