| 主权项 |
1. 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, 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 X3 is independently O, S, NR6, C(═O) or CR7R7a; X4 is (CR7R7a)n,O, S or NR6;is carbocyclyl or heterocyclyl;
each Y1 and Y2 is independently N or 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; e is 0, 1, 2, 3 or 4 with the proviso that where X3 is O, S or NR6, e is 1; f 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 optical 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, 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, aryl alkylamino, 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, 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)—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—, 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; wherein each of —(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(R19)—(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)—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(═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)—, 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, 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. |
