Pyrazolone-fused pyrimidine compound, preparation method for same and applications thereof

A pyrazolone-fused pyrimidine compound represented by formula II, a pharmaceutically acceptable salt thereof, a solvate thereof, a solvate of the pharmaceutically acceptable salt thereof, a metabolite thereof or a prodrug thereof:

• wherein, A is C3-C20 cycloalkyl substituted by one or two R1;
• X is CH or N;
• R1 is independently halogen, —OR1-1, —SR1-2, —CN, —NR1-3R1-4, —C(═O)R1-5, —C(═NR1-6)R1-7, ═N—O—R1-9 or “C2-C7 alkenyl, C2-C8 alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, C6-C10 aryl or C1-C7 heteroaryl” optionally substituted by one, two or three R1-8;
• R1-1 is independently “C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, C6-C10 aryl, or C1-C7 heteroaryl” optionally substituted by one, two or three R1-1-1;
• R1-1-1 is independently halogen, hydroxyl, amino, mercapto, cyano, C1-C7 alkyl, C1-C7 alkoxy, C1-C7 alkylthio, C2-C7 alkenyl, C2-C7 alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, C6-C10 aryl, C1-C7 heteroaryl or “amino substituted by one or two R1-1-1-1”;
• R1-1-1-1 is independently C1-C7 alkyl or C3-C14 cycloalkyl;
• R1-2 is independently hydrogen or “C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, C6-C10 aryl, or C1-C7 heteroaryl” optionally substituted by one, two or three R1-2-1;
• R1-2-1 is independently hydrogen, halogen, hydroxyl, amino, mercapto, cyano, C1-C7 alkyl, C1-C7 alkoxy, C1-C7 alkylthio, C2-C7 alkenyl, C2-C7 alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, C6-C10 aryl, C1-C7 heteroaryl or “amino substituted by one or two R1-2-1-1”;
• R1-2-1-1 is independently C1-C7 alkyl or C3-C14 cycloalkyl;
• R1-3 and R1-4 are independently hydrogen, —S(═O)2R1-3-1, —C(O)R1-3-2, —C(═NR1-3-3)NR1-3-5R1-3-6, S(═O)2NR1-3-7R1-3-8, —C(═O)NR1-3-9R1-3-10 or “C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, C6-C10 aryl or C1-C7 heteroaryl” optionally substituted by one, two or three R1-3-11;
• or, R1-3 and R1-4 together with a nitrogen atom they are attached to form a C3-C14 heterocycloalkyl optionally substituted by one, two or three R1-3-12;
• one or more methylenes in the C3-C14 heterocycloalkyl are optionally and independently substituted by oxygen atom, sulfur atom, sulfinyl, sulfonyl, carbonyl, vinylidene or —N(R1-3-3)—;
• R1-3-13 is independently C1-C7 alkyl or C3-C14 cycloalkyl;
• R1-3-1 and R1-3-2 are independently “C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl or C6-C10 aryl” optionally substituted by one or two R1-3-1-1;
• R1-3-1-1 is independently C1-C7 alkyl or C3-C14 cycloalkyl;
• R1-3-3 is independently hydrogen, —CN, C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl or C3-C14 cycloalkyl;
• R1-3-5, R1-3-6, R1-3-7, R1-3-8, R1-3-9 and R1-3-10 are independently hydrogen, C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl or C3-C14 cycloalkyl;
• or, R1-3-5 and R1-3-6 together with a nitrogen atom they are attached to form a C3-C14 heterocycloalkyl optionally substituted by one, two or three R1-3-5-1;
• one or more methylenes in the C3-C14 heterocycloalkyl are optionally and independently substituted by oxygen atom, sulfur atom, sulfinyl, sulfonyl, carbonyl, vinylidene or —N(R1-3-5-2)—;
• R1-3-5-1 is independently C1-C7 alkyl or C3-C14 cycloalkyl;
• R1-3-5-2 is independently C1-C7 alkyl or C3-C14 cycloalkyl;
• or, R1-3-7 and R1-3-8 together with a nitrogen atom they are attached to form a C3-C14 heterocycloalkyl optionally substituted by one, two or three R1-3-7-1;
• one or more methylenes in the C3-C14 heterocycloalkyl are optionally and independently substituted by oxygen atom, sulfur atom, sulfinyl, sulfonyl, carbonyl, vinylidene or —N(R1-3-7-2)—;
• R1-3-7-1 is independently C1-C7 alkyl or C3-C14 cycloalkyl;
• R1-3-7-2 is independently C1-C7 alkyl or C3-C14 cycloalkyl;
• or, R1-3-9 and R1-3-10 together with a nitrogen atom they are attached to form a C3-C14 heterocycloalkyl optionally substituted by one, two or three R1-3-9-1;
• one or more methylenes in the C3-C14 heterocycloalkyl are optionally and independently substituted by oxygen atom, sulfur atom, sulfinyl, sulfonyl, carbonyl, vinylidene or —N(R1-3-9-2)—;
• R1-3-9-1 is independently C1-C7 alkyl or C3-C14 cycloalkyl;
• R1-3-9-2 is independently C1-C7 alkyl or C3-C14 cycloalkyl;
• R1-3-11 is independently halogen, hydroxyl, amino, mercapto, cyano, C1-C7 alkyl, C1-C7 alkoxy, C1-C7 alkylthio, C2-C7 alkenyl, C2-C7 alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, C6-C10 aryl, C1-C7 heteroaryl or “amino substituted by one or two R1-3-11-1”;
• R1-3-11-1 is independently C1-C7 alkyl or C3-C14 cycloalkyl;
• R1-3-12 is independently halogen, hydroxyl, amino, mercapto, cyano, C1-C7 alkyl, C1-C7 alkoxy, C1-C7 alkylthio, C2-C7 alkenyl, C2-C7 alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, C6-C10 aryl, C1-C7 heteroaryl or “amino substituted by one or two R1-3-12-1”;
• R1-3-12-1 is independently C1-C7 alkyl or C3-C14 cycloalkyl;
• R1-5 is independently hydrogen, —NR1-5-1R1-5-2, —OR1-5-3 or “C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, C6-C10 aryl, or C1-C7 heteroaryl” optionally substituted by one, two or three R1-5-4;
• R1-5-1 and R1-5-2 are independently hydrogen, C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl or C3-C14 cycloalkyl;
• or, R1-5-1 and R1-5-2 together with a nitrogen atom they are attached to form a C3-C14 heterocycloalkyl optionally substituted by one, two or three R1-5-1-1;
• one or more methylenes in the C3-C14 heterocycloalkyl are optionally and independently substituted by oxygen atom, sulfur atom, sulfinyl, sulfonyl, carbonyl, vinylidene or —N(R1-5-1-2)—;
• R1-5-1-1 is independently C1-C7 alkyl or C3-C14 cycloalkyl;
• R1-5-1-2 is independently C1-C7 alkyl or C3-C14 cycloalkyl;
• R1-5-3 is independently hydrogen, C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, C6-C10 aryl or C1-C7 heteroaryl;
• R1-5-4 is independently halogen, hydroxyl, amino, mercapto, cyano, C1-C7 alkyl, C1-C7 alkoxy, C1-C7 alkylthio, C2-C7 alkenyl, C2-C7 alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, C6-C10 aryl, C1-C7 heteroaryl or “amino substituted by one or two R1-5-4-1”;
• R1-5-4-1 is independently C1-C7 alkyl or C3-C14 cycloalkyl;
• R1-6 is independently hydrogen, —CN, —OH or “C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, C6-C10 aryl, or C1-C7 heteroaryl” optionally substituted by one, two or three R1-6-1;
• R1-6-1 is independently halogen, hydroxyl, amino, mercapto, cyano, C1-C7 alkyl, C1-C7 alkoxy, C1-C7 alkylthio, C2-C7 alkenyl, C2-C7 alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, C6-C10 aryl, C1-C7 heteroaryl or “amino substituted by one or two R1-6-1-1”;
• R1-6-1-1 is independently C1-C7 alkyl or C3-C14 cycloalkyl;
• R1-7 is independently hydrogen, —OR1-7-1, —NR1-7-2R1-7-3 or “C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, C6-C10 aryl or C1-C7 heteroaryl” optionally substituted by one, two or three R1-7-4;
• R1-7-1 is independently hydrogen, C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, C6-C10 aryl or C1-C7 heteroaryl;
• R1-7-2 and R1-7-3 are independently C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl or C3-C14 cycloalkyl;
• or, R1-7-2 and R1-7-3 together with a nitrogen atom they are attached to form a C3-C14 heterocycloalkyl optionally substituted by one, two or three R1-7-2-1;
• one or more methylenes in the C3-C14 heterocycloalkyl are optionally and independently substituted by oxygen atom, sulfur atom, sulfinyl, sulfonyl, carbonyl, vinylidene or —N(R1-7-2-2)—;
• R1-7-2-1 is independently C1-C7 alkyl or C3-C14 cycloalkyl;
• R1-7-2-2 is independently C1-C7 alkyl or C3-C14 cycloalkyl;
• R1-7-4 is independently halogen, hydroxyl, amino, mercapto, cyano, C1-C7 alkyl, C1-C7 alkoxy, C1-C7 alkylthio, C2-C7 alkenyl, C2-C7 alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, C6-C10 aryl, C1-C7 heteroaryl or “amino substituted by one or two R1-7-4-1”;
• R1-7-4-1 is independently C1-C7 alkyl or C3-C14 cycloalkyl;
• R1-8 is independently oxo, halogen, —OH, amino, mercapto, cyano, C1-C7 alkyl, C1-C7 alkoxy, C1-C7 alkylthio, C2-C7 alkenyl, C2-C7 alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, C6-C10 aryl, C1-C7 heteroaryl or “amino substituted by one or two R1-8-1”;
• R1-8-1 is independently C1-C7 alkyl or C3-C14 cycloalkyl;
• R1-9 is independently hydrogen or C1-C7 alkyl;
• R2 is —OR2-1, cyano, carboxyl;
• or “C2-C7 alkyl, C3-C14 cycloalkyl or C3-C14 heterocycloalkyl” optionally substituted by one, two or three R2-2;
• R2-1 is C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, C6-C10 aryl or C1-C7 heteroaryl;
• R2-2 is independently halogen, hydroxyl, amino, C1-C7 alkyl, C1-C7 alkoxy, C3-C14 cycloalkyl or C3-C14 heterocycloalkyl;
• the C3-C14 heterocycloalkyl, and C1-C7 heteroaryl independently have 1, 2, 3, or 4 heteroatoms selected from one or more of boron, silicon, oxygen, sulfur, selenium, nitrogen and phosphorus.