Aromatic heterocyclic substituted olefin compound, preparation method for same, pharmaceutical composition of same, and applications thereof

An aromatic heterocyclic substituted olefin compound represented by general formula I or a pharmaceutically acceptable salt thereof:

• wherein ring A and ring B are located on the same side of the double bond;
• is
• R3, R31, R32, R33, R3a, R3a1, R3b, R3b1, R3c, R3c1, R3c2, R3d, R3d1, R3d2, R3e, R3e1, R3f, R3f1, R3f2, R3g and R3g1 are each independently hydrogen, halogen, cyano, nitro, —NRa3Ra4,—ORa5, —SRa6, —C(O)ORa7, —C(O)NRa8Ra9, —CORa10, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-8 alkenyl, substituted or unsubstituted C2-8 alkynyl, substituted or unsubstituted C3-10 cycloalkyl, substituted or unsubstituted C2-8 heterocycloalkyl, substituted or unsubstituted C4-8 cycloalkenyl, substituted or unsubstituted C6-20 aryl, or substituted or unsubstituted C2-10 heteroaryl;
• wherein Ra3, Ra4, Ra5, Ra6, Ra7, Ra8, Ra9 and Ra10 are each independently hydrogen, substituted or unsubstituted C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, C3-10 cycloalkyl, C2-8 heterocycloalkyl, C6-20 aryl or C2-10 heteroaryl;
• Ra3 and Ra8 can also be independently hydroxyl or C1-6 alkoxy;
• substituents in the substituted C1-6 alkyl in R3, R31, R32, R33, R3a, R3a1, R3b, R3b1, R3c, R3c1, R3c2, R3d, R3d1, R3d2, R3e, R3e1, R3f, R3f1, R3f2, R3g, R3g1, Ra3, Ra4, Ra5, Ra6, Ra7, Ra8, Ra9 and Ra10, and substituents in the substituted C2-8 alkenyl, substituted C2-8 alkynyl, substituted C3-10 cycloalkyl, substituted C2-8 heterocycloalkyl, substituted C4-8 cycloalkenyl, substituted C6-20 aryl, and substituted C2-10 heteroaryl in R3, R31, R32, R33, R3a, R3a1, R3b, R3b1, R3c, R3c1, R3c2, R3d, R3d1, R3d2, R3e, R3e1, R3f, R3f1, R3f2, R3g and R3g1 are each independently one or more of the following groups:
• deuterium, halogen, cyano, C1-6 alkyl, halogen substituted C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, —ORa15, —SRa16, —C(O)ORa17, —CORa18, —C(O)NH2, C3-10 cycloalkyl, C2-8 heterocycloalkyl, C6-20 aryl or C2-10 heteroaryl;
• Ra15, Ra16, Ra17 and Ra18 are each independently hydrogen or C1-6 alkyl;
• when there are multiple substituents, the substituents are the same or different;
• R4 is hydrogen, cyano, C1-6 alkyl, C3-10 cycloalkyl, C2-8 heterocycloalkyl, —C(O)ORa19 or C1-6 alkyl substituted with —ORa20;
• Ra19 and Ra20 are each independently C1-6 alkyl;
• is
• R5, R51, R5a, R5a1, R5a2, R5b, R5b1, R5c, R5c1, R5c2, R5d, R5d1, R5d2, R5e, R5e1 and R5e2, are each independently hydrogen, deuterium or halogen;
• R6, R6a, R6b, R6c, R6d and R6e are each independently hydrogen, deuterium, halogen, sulfonyl, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-8 alkenyl, substituted or unsubstituted C2-8 alkynyl, substituted or unsubstituted C3-10 cycloalkyl, substituted or unsubstituted C2-8 heterocycloalkyl, substituted or unsubstituted C6-20 aryl, substituted or unsubstituted C2-10 heteroaryl, cyano, —OR61, —SR62, —NRa63Ra64, —C(O)R65, —C(O)OR66, —OC(O)R67, —OC(O)OR68, —(O)NRa69Ra610, —N(R611)C(O)R612, —S(O)R613, —S(O)2R614 —S(O)2NRa615Ra616, —OC(O)NRa617Ra618, —N(R619)C(O)R620, —N(R621)C(O)NRa622Ra623, —N(R624)S(O)2R625 or —OP(O)(OR626)2;
• R61, R62, Ra64, R65, R66, R67, R68, Ra610, R611, R612, R613, R614, Ra615, Ra616, Ra617, Ra618, R619, R620, R621, Ra622, Ra623, R624, R625 and R626 are each independently hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-8 alkenyl, substituted or unsubstituted C2-8 alkynyl, substituted or unsubstituted C3-10 cycloalkyl, substituted or unsubstituted C2-8 heterocycloalkyl, substituted or unsubstituted C6-20 aryl, or substituted or unsubstituted C2-10 heteroaryl;
• Ra63 and Ra69 are each independently hydrogen, hydroxyl, C1-6 alkoxy, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-8 alkenyl, substituted or unsubstituted C2-8 alkynyl, Substituted or unsubstituted C3-10 cycloalkyl, substituted or unsubstituted C2-8 heterocycloalkyl, substituted or unsubstituted C6-20 aryl, or substituted or unsubstituted C2-10 heteroaryl;
• in R6, R6a, R6b, R6c, R6d and R6e, substituents in the substituted C1-6 alkyl, substituted C2-8 alkenyl, substituted C2-8 alkynyl, substituted C3-10 cycloalkyl, substituted C2-8 heterocycloalkyl, substituted C6-20 aryl, and substituted C2-10 heteroaryl are each independently one or more of the following groups:
• deuterium, halogen, C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, C3-10 cycloalkyl, C2-8 heterocycloalkyl, C6-20 aryl, C2-10 heteroaryl, cyano, —OR71, —SR72, —NRa73Ra74, —C(O)R75, —C(O)OR76, —OC(O)R77, —OC(O)OR78, —C(O)NRa79Ra710, —N(R711)C(O)R712, S(O)R713, —S(O)2R714, —S(O)2NRa715Ra716, —OC(O)NRa717Ra718, —N(R719)C(O)OR720, —N(R721)C(O)NRa722Ra723, —NR724)S(O)2R725 or —OP(O)(OR726)2;
• when there are multiple substituents, the substituents are the same or different;
• R71, R72, Ra73, Ra74, R75, R76, R77, R78, Ra79, Ra710, R711, R712, R713, R714, Ra715, Ra716, Ra717, Ra718, R719, R720, R721, Ra722, Ra723, R724, R725 and R726 are each independently deuterium, C1-6 alkyl, halogen substituted C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, C3-10 cycloalkyl, C2-8 heterocycloalkyl, C6-20 aryl or C2-10 heteroaryl;
• in R61, R62, Ra63, Ra64, R65, R66, R67, R68, Ra69, Ra610, R611, R612, R613, R614, Ra615, Ra616, Ra617, Ra618, R619, R620, R621, Ra622, Ra623, R624, R625 and R626, substituents in the substituted C1-6 alkyl, substituted C2-8 alkenyl, substituted C2-8 alkynyl, substituted C3-10 cycloalkyl, substituted C2-8 heterocycloalkyl, substituted C6-20 aryl or substituted C2-10 heteroaryl are one or more of the following groups:
• deuterium, halogen, cyano, C1-6 alkyl, halogen substituted C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, C3-10 cycloalkyl, C2-8 heterocycloalkyl, C6-20 aryl, C2-10 heteroaryl, —ORc, —SRc1, —NRb1Rb2, —C(O)Rc2, —C(O)ORc3, —OC(O)Rc4, —OC(O)ORc5, —C(O)NRb3Rb4,—N(Rc6)C(O)ORc7, S(O)Rc8, —S(O)2Rc9, —S(O)2NRb5Rb6, —N(Rc10)c(O)Rc11, —N(Rc12)C(O)NRb7Rb8 or —N(Rc13)S(O)2Rc14, Rc, Rc1, Rb1, Rb2, Rc2, Rc3, Rc4, Rc5, Rb3, Rb4, Rc6, Rc7, Rc8, Rc9, Rb5, Rb6, Rc10, Rc11, Rc12, Rb7, Rb8, Rc13 and Rc14 are each independently hydrogen, hydroxyl, C1-6 alkyl, halogen substituted C1-6 alkyl, C3-10 cycloalkyl, C2-8 heterocycloalkyl, C6-20 aryl or C2-10 heteroaryl;
• R7, R8, R9, R10, R11, R12 and R13 are each independently hydrogen, deuterium or halogen;
• one of R1 and R2 is hydrogen, deuterium, halogen, or substituted or unsubstituted C1-6 alkyl, and the other is hydrogen, deuterium, halogen, cyano, sulfonyl, substituted or unsubstituted C1-6 alkyl, —C(O)OR91, —COR92,
• —S(O)R95, —S(O)2R96, —C(O)NR97R98, or substituted or unsubstituted C2-10 heteroaryl;
• in R1 and R2, substituents in the substituted C1-6 alkyl and the substituted C2-10 heteroaryl are each independently one or more of the following groups:
• deuterium, halogen, cyano, C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, —OR920, —SR921, —C(O)OR922, —COR923, —C(O)NH2, —NR924R925, C3-10 cycloalkyl, C2-8 heterocycloalkyl, C6-20 aryl or C2-10 heteroaryl;
• R921, R922, R923, R924 and R925 are each independently hydrogen or C1-6 alkyl, wherein R1 is not cyano;
• R91, R92, R93 and R94 are independently one or more of the following groups hydrogen, C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, C3-10 cycloalkyl, C2-8 heterocycloalkyl, C6-20 aryl or C2-10 heteroaryl;
• R95 and R96 are independently hydrogen or C1-6 alkyl;
• R97 and R98 are independently hydroxyl, hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-8 alkenyl, substituted or unsubstituted C2-8 alkynyl, substituted or unsubstituted C3-10 cycloalkyl, substituted or unsubstituted C2-8 heterocycloalkyl, substituted or unsubstituted C6-20 aryl, or substituted or unsubstituted C2-10 heteroaryl;
• in R97 and R98, substituents in the substituted C1-6 alkyl, substituted C2-8 alkenyl, substituted C2-8 alkynyl, substituted C3-10 cycloalkyl, substituted C2-8 heterocycloalkyl, substituted C6-20 aryl, and substituted C2-10 heteroaryl are each independently one or more of the following groups:
• deuterium, halogen, cyano, C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, C3-10 cycloalkyl, C2-8 heterocycloalkyl, C6-20 aryl, C2-10 heteroaryl, —OR101, —SR102, —NRb103Rb104, —C(O)R105, —C(O)OR106, —OC(O)R107, —OC(O)OR108, —C(O)NRb109Rb1010, —N(R1011)C(O)OR1012, S(O)R1013, —S(O)2R1014, —S(O)2NRb1015Rb1016, —N(R1017)C(O)OR1018, —OC(O)NRb1019Rb1020, —N(R1021)S(O)2R1022;
• when there are multiple substituents, the substituents are the same or different;
• R101, R102, Rb103, Rb104, R105, R106, R107, R108, Rb109, Rb1010, R1011, R1012, R1013, R1014, Rb1015, Rb1016, R1017, R1018, Rb1019, Rb1020, R1021 and R1022 are each independently hydrogen, hydroxyl, C1-6 alkyl, halogen substituted C1-6 alkyl, C3-10 cycloalkyl, C2-8 heterocycloalkyl, C6-20 aryl or C2-10 heteroaryl;
• or R1 and R2 together with the carbon atom to which they are attached form substituted or unsubstituted 4-8 membered cycloalkenyl, or a substituted or unsubstituted 4-8 membered heterocycle, and the heteroatoms in the 4-8 membered heterocycle are one or more of O, S and N, and the number of the heteroatoms is 1, 2, 3 or 4;
• substituents in the substituted 4-8 membered cycloalkenyl and the substituted 4-8 membered heterocycle are each independently one or more of the following groups:
• deuterium, halogen, cyano, C1-6 alkyl, halogen substituted C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, —OR111, —SR112, —C(O)OR113, —COR114, —C(O)NH2, C3-10 cycloalkyl, C2-8 heterocycloalkyl, C6-20 aryl or C2-10 heteroaryl;
• R111, R112, R113 and R114 are each independently hydrogen or C1-6 alkyl;
• in each of the above letters and groups, the heteroatoms in the substituted or unsubstituted C2-8 heterocycloalkyl or the C2-8 heterocycloalkyl are one or more of N, O and S, and the number of the heteroatoms is 1, 2, 3 or 4;
• the heteroatoms in the substituted or unsubstituted C2-10 heteroaryl or the C2-10 heteroaryl are one or more of N, O and S, and the number of the heteroatoms is 1, 2, 3 or 4;
• when there are multiple heteroatoms, the heteroatoms are the same or different;
• or in the above groups or substituents, when NRXRY is present, then RX and RY together with the nitrogen atom to which they are attached form substituted or unsubstituted 3-8 membered heterocyclyl;
• the heteroatoms in the 3-8 membered heterocyclyl are N, N and O, N and S, or N, O and S;
• the number of the heteroatoms is 1, 2, 3 or 4;
• the substituents in the substituted 3-8 membered heterocyclyl are one or more of the following groups:
• deuterium, halogen, cyano, C1-6 alkyl, halogen substituted C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, —ORa81, —SRa82, —C(O)ORa83, —CORa84, —C(O)NH2, C3-10 cycloalkyl, C2-8 heterocycloalkyl, C6-20 aryl or C2-10 heteroaryl;
• Ra81, Ra82, Ra83 and Ra84 are each independently hydrogen or C1-6 alkyl;
• NRXRY is —NRa3Ra4, —NRa8Ra9, —NRa63Ra64, —NRa69Ra610, —NRa615Ra616, —NRa617Ra618, —NRa622Ra623, —NRa73Ra74, —NRa79Ra710, —NRa715Ra716, —NRa717Ra718, —NRa722Ra723, —NRb1Rb2, —NRb3Rb4, —NRb5Rb6, —NRb7Rb8, —NR93R94, —NR97R98, —NR924R925, —NRb103Rb104, —NRb109Rb1010, —NRb1015Rb1016 or —NRb1019Rb1020.