Pyrazolone-Fused Pyrimidine Compound, Preparation Method for Same and Applications Thereof

Abstract

Disclosed are a pyrazolone-fused pyrimidine compound, a preparation method for same and applications thereof. Provided in the present invention is the pyrazolone-fused pyrimidine compound as represented by formula (II). The compound has improved inhibitory activity with respect to WEE1 kinase.

##STR00001##

Claims

1. 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: ##STR00199## wherein, A is C.sub.3-C.sub.20 cycloalkyl substituted by one or two R.sup.1; X is CH or N; R.sup.1 is independently halogen, —OR.sup.1-1, —SR.sup.1-2, —CN, —NR.sup.1-3R.sup.1-4, —C(═O)R.sup.1-5, —C(═NR.sup.1-6)R.sup.1-7, ═N—O—R.sup.1-9 or “C.sub.2-C.sub.7 alkenyl, C.sub.2-C.sub.8 alkynyl, C.sub.3-C.sub.14 cycloalkyl, C.sub.3-C.sub.14 heterocycloalkyl, C.sub.6-C.sub.10 aryl or C.sub.1-C.sub.7 heteroaryl” optionally substituted by one, two or three R.sup.1-8; R.sup.1-1 is independently “C.sub.1-C.sub.7 alkyl, C.sub.2-C.sub.7 alkenyl, C.sub.2-C.sub.7 alkynyl, C.sub.3-C.sub.14 cycloalkyl, C.sub.3-C.sub.14 heterocycloalkyl, C.sub.6-C.sub.10 aryl, or C.sub.1-C.sub.7 heteroaryl” optionally substituted by one, two or three R.sup.1-1-1; R.sup.1-1-1 is independently halogen, hydroxyl, amino, mercapto, cyano, C.sub.1-C.sub.7 alkyl, C.sub.1-C.sub.7 alkoxy, C.sub.1-C.sub.7 alkylthio, C.sub.2-C.sub.7 alkenyl, C.sub.2-C.sub.7 alkynyl, C.sub.3-C.sub.14 cycloalkyl, C.sub.3-C.sub.14 heterocycloalkyl, C.sub.6-C.sub.10 aryl, C.sub.1-C.sub.7 heteroaryl or “amino substituted by one or two R.sup.1-1-1-1”; R.sup.1-1-1-1 is independently C.sub.1-C.sub.7 alkyl or C.sub.3-C.sub.14 cycloalkyl; R.sup.1-2 is independently hydrogen or “C.sub.1-C.sub.7 alkyl, C.sub.2-C.sub.7 alkenyl, C.sub.2-C.sub.7 alkynyl, C.sub.3-C.sub.14 cycloalkyl, C.sub.3-C.sub.14 heterocycloalkyl, C.sub.6-C.sub.10 aryl, or C.sub.1-C.sub.7 heteroaryl” optionally substituted by one, two or three R.sup.1-2-1; R.sup.1-2-1 is independently hydrogen, halogen, hydroxyl, amino, mercapto, cyano, C.sub.1-C.sub.7 alkyl, C.sub.1-C.sub.7 alkoxy, C.sub.1-C.sub.7 alkylthio, C.sub.2-C.sub.7 alkenyl, C.sub.2-C.sub.7 alkynyl, C.sub.3-C.sub.14 cycloalkyl, C.sub.3-C.sub.14 heterocycloalkyl, C.sub.6-C.sub.10 aryl, C.sub.1-C.sub.7 heteroaryl or “amino substituted by one or two R.sup.1-2-1-1”; R.sup.1-2-1-1 is independently C.sub.1-C.sub.7 alkyl or C.sub.3-C.sub.14 cycloalkyl; R.sup.1-3 and R.sup.1-4 are independently hydrogen, —S(═O).sub.2R.sup.1-3-1, —C(═O)R.sup.1-3-2, —C(═NR.sup.1-3-3)NR.sup.1-3-5R.sup.1-3-6, —S(═O).sub.2NR.sup.1-3-7R.sup.1-3-8, —C(═O)NR.sup.1-3-9R.sup.1-3-10 or “C.sub.1-C.sub.7 alkyl, C.sub.2-C.sub.7 alkenyl, C.sub.2-C.sub.7 alkynyl, C.sub.3-C.sub.14 cycloalkyl, C.sub.3-C.sub.14 heterocycloalkyl, C.sub.6-C.sub.10 aryl or C.sub.1-C.sub.7 heteroaryl” optionally substituted by one, two or three R.sup.1-3-11; or, R.sup.1-3 and R.sup.1-4 together with the nitrogen atom they are attached to form a C.sub.3-C.sub.14 heterocycloalkyl optionally substituted by one, two or three R.sup.1-3-12; one or more methylenes in the C.sub.3-C.sub.14 heterocycloalkyl are optionally and independently substituted by oxygen atom, sulfur atom, sulfinyl, sulfonyl, carbonyl, vinylidene or —N(R.sup.1-3-13)—; R.sup.1-3-13 is independently C.sub.1-C.sub.7 alkyl or C.sub.3-C.sub.14 cycloalkyl; R.sup.1-3-1 and R.sup.1-3-2 are independently “C.sub.1-C.sub.7 alkyl, C.sub.2-C.sub.7 alkenyl, C.sub.2-C.sub.7 alkynyl, C.sub.3-C.sub.14 cycloalkyl, C.sub.3-C.sub.14 heterocycloalkyl or C.sub.6-C.sub.10 aryl” optionally substituted by one or two R.sup.1-3-1-1; R.sup.1-3-1-1 is independently C.sub.1-C.sub.7 alkyl or C.sub.3-C.sub.14 cycloalkyl; R.sup.1-3-3 is independently hydrogen, —CN, C.sub.1-C.sub.7 alkyl, C.sub.2-C.sub.7 alkenyl, C.sub.2-C.sub.7 alkynyl or C.sub.3-C.sub.14 cycloalkyl; R.sup.1-3-5, R.sup.1-3-6, R.sup.1-3-7, R.sup.1-3-8, R.sup.1-3-9 and R.sup.1-3-10 are independently hydrogen, C.sub.1-C.sub.7 alkyl, C.sub.2-C.sub.7 alkenyl, C.sub.2-C.sub.7 alkynyl or C.sub.3-C.sub.14 cycloalkyl; or, R.sup.1-3-5 and R.sup.1-3-6 together with the nitrogen atom they are attached to form a C.sub.3-C.sub.14 heterocycloalkyl optionally substituted by one, two or three R.sup.1-3-5-1; one or more methylenes in the C.sub.3-C.sub.14 heterocycloalkyl are optionally and independently substituted by oxygen atom, sulfur atom, sulfinyl, sulfonyl, carbonyl, vinylidene or —N(R.sup.1-3-5-2)—; R.sup.1-3-5-1 is independently C.sub.1-C.sub.7 alkyl or C.sub.3-C.sub.14 cycloalkyl; R.sup.1-3-5-2 is independently C.sub.1-C.sub.7 alkyl or C.sub.3-C.sub.14 cycloalkyl; or, R.sup.1-3-7 and R.sup.1-3-8 together with the nitrogen atom they are attached to form a C.sub.3-C.sub.14 heterocycloalkyl optionally substituted by one, two or three R.sup.1-3-7-1; one or more methylenes in the C.sub.3-C.sub.14 heterocycloalkyl are optionally and independently substituted by oxygen atom, sulfur atom, sulfinyl, sulfonyl, carbonyl, vinylidene or —N(R.sup.1-3-7-2)—; R.sup.1-3-7-1 is independently C.sub.1-C.sub.7 alkyl or C.sub.3-C.sub.14 cycloalkyl; R.sup.1-3-7-2 is independently C.sub.1-C.sub.7 alkyl or C.sub.3-C.sub.14 cycloalkyl; or, R.sup.1-3-9 and R.sup.1-3-10 together with the nitrogen atom they are attached to form a C.sub.3-C.sub.14 heterocycloalkyl optionally substituted by one, two or three R.sup.1-3-9-1; one or more methylenes in the C.sub.3-C.sub.14 heterocycloalkyl are optionally and independently substituted by oxygen atom, sulfur atom, sulfinyl, sulfonyl, carbonyl, vinylidene or —N(R.sup.1-3-9-2)—; R.sup.1-3-9-1 is independently C.sub.1-C.sub.7 alkyl or C.sub.3-C.sub.14 cycloalkyl; R.sup.1-3-9-2 is independently C.sub.1-C.sub.7 alkyl or C.sub.3-C.sub.14 cycloalkyl; R.sup.1-3-11 is independently halogen, hydroxyl, amino, mercapto, cyano, C.sub.1-C.sub.7 alkyl, C.sub.1-C.sub.7 alkoxy, C.sub.1-C.sub.7 alkylthio, C.sub.2-C.sub.7 alkenyl, C.sub.2-C.sub.7 alkynyl, C.sub.3-C.sub.14 cycloalkyl, C.sub.3-C.sub.14 heterocycloalkyl, C.sub.6-C.sub.10 aryl, C.sub.1-C.sub.7 heteroaryl or “amino substituted by one or two R.sup.1-3-11”; R.sup.1-3-11-1 is independently C.sub.1-C.sub.7 alkyl or C.sub.3-C.sub.14 cycloalkyl; R.sup.1-3-12 is independently halogen, hydroxyl, amino, mercapto, cyano, C.sub.1-C.sub.7 alkyl, C.sub.1-C.sub.7 alkoxy, C.sub.1-C.sub.7 alkylthio, C.sub.2-C.sub.7 alkenyl, C.sub.2-C.sub.7 alkynyl, C.sub.3-C.sub.14 cycloalkyl, C.sub.3-C.sub.14 heterocycloalkyl, C.sub.6-C.sub.10 aryl, C.sub.1-C.sub.7 heteroaryl or “amino substituted by one or two R.sup.1-3-12-1”; R.sup.1-3-12-1 is independently C.sub.1-C.sub.7 alkyl or C.sub.3-C.sub.14 cycloalkyl; R.sup.1-5 is independently hydrogen, —NR.sup.1-5-1R.sup.1-5-2, —OR.sup.1-5-3 or “C.sub.1-C.sub.7 alkyl, C.sub.2-C.sub.7 alkenyl, C.sub.2-C.sub.7 alkynyl, C.sub.3-C.sub.14 cycloalkyl, C.sub.3-C.sub.14 heterocycloalkyl, C.sub.6-C.sub.10 aryl, or C.sub.1-C.sub.7 heteroaryl” optionally substituted by one, two or three R.sup.1-5-4; R.sup.1-5-1 and R.sup.1-5-2 are independently hydrogen, C.sub.1-C.sub.7 alkyl, C.sub.2-C.sub.7 alkenyl, C.sub.2-C.sub.7 alkynyl or C.sub.3-C.sub.14 cycloalkyl; or, R.sup.1-5-1 and R.sup.1-5-2 together with the nitrogen atom they are attached to form a C.sub.3-C.sub.14 heterocycloalkyl optionally substituted by one, two or three R.sup.1-5-1-1; one or more methylenes in the C.sub.3-C.sub.14 heterocycloalkyl are optionally and independently substituted by oxygen atom, sulfur atom, sulfinyl, sulfonyl, carbonyl, vinylidene or —N(R.sup.1-5-1-2)—; R.sup.1-5-1-1 is independently C.sub.1-C.sub.7 alkyl or C.sub.3-C.sub.14 cycloalkyl; R.sup.1-5-1-2 is independently C.sub.1-C.sub.7 alkyl or C.sub.3-C.sub.14 cycloalkyl; R.sup.1-5-3 is independently hydrogen, C.sub.1-C.sub.7 alkyl, C.sub.2-C.sub.7 alkenyl, C.sub.2-C.sub.7 alkynyl, C.sub.3-C.sub.14 cycloalkyl, C.sub.3-C.sub.14 heterocycloalkyl, C.sub.6-C.sub.10 aryl or C.sub.1-C.sub.7 heteroaryl; R.sup.1-5-4 is independently halogen, hydroxyl, amino, mercapto, cyano, C.sub.1-C.sub.7 alkyl, C.sub.1-C.sub.7 alkoxy, C.sub.1-C.sub.7 alkylthio, C.sub.2-C.sub.7 alkenyl, C.sub.2-C.sub.7 alkynyl, C.sub.3-C.sub.14 cycloalkyl, C.sub.3-C.sub.14 heterocycloalkyl, C.sub.6-C.sub.10 aryl, C.sub.1-C.sub.7 heteroaryl or “amino substituted by one or two R.sup.1-5-4-1”; R.sup.1-5-4-1 is independently C.sub.1-C.sub.7 alkyl or C.sub.3-C.sub.14 cycloalkyl; R.sup.1-6 is independently hydrogen, —CN, —OH or “C.sub.1-C.sub.7 alkyl, C.sub.2-C.sub.7 alkenyl, C.sub.2-C.sub.7 alkynyl, C.sub.3-C.sub.14 cycloalkyl, C.sub.3-C.sub.14 heterocycloalkyl, C.sub.6-C.sub.10 aryl, or C.sub.1-C.sub.7 heteroaryl” optionally substituted by one, two or three R.sup.1-6-1; R.sup.1-6-1 is independently halogen, hydroxyl, amino, mercapto, cyano, C.sub.1-C.sub.7 alkyl, C.sub.1-C.sub.7 alkoxy, C.sub.1-C.sub.7 alkylthio, C.sub.2-C.sub.7 alkenyl, C.sub.2-C.sub.7 alkynyl, C.sub.3-C.sub.14 cycloalkyl, C.sub.3-C.sub.14 heterocycloalkyl, C.sub.6-C.sub.10 aryl, C.sub.1-C.sub.7 heteroaryl or “amino substituted by one or two R.sup.1-6-1-1”; R.sup.1-6-1-1 is independently C.sub.1-C.sub.7 alkyl or C.sub.3-C.sub.14 cycloalkyl; R.sup.1-7 is independently hydrogen, —OR.sup.1-7-1, —NR.sup.1-7-2R.sup.1-7-3 or “C.sub.1-C.sub.7 alkyl, C.sub.2-C.sub.7 alkenyl, C.sub.2-C.sub.7 alkynyl, C.sub.3-C.sub.14 cycloalkyl, C.sub.3-C.sub.14 heterocycloalkyl, C.sub.6-C.sub.10 aryl or C.sub.1-C.sub.7 heteroaryl” optionally substituted by one, two or three R.sup.1-7-4; R.sup.1-7-1 is independently hydrogen, C.sub.1-C.sub.7 alkyl, C.sub.2-C.sub.7 alkenyl, C.sub.2-C.sub.7 alkynyl, C.sub.3-C.sub.14 cycloalkyl, C.sub.3-C.sub.14 heterocycloalkyl, C.sub.6-C.sub.10 aryl or C.sub.1-C.sub.7 heteroaryl; R.sup.1-7-2 and R.sup.1-7-3 are independently C.sub.1-C.sub.7 alkyl, C.sub.2-C.sub.7 alkenyl, C.sub.2-C.sub.7 alkynyl or C.sub.3-C.sub.14 cycloalkyl; or, R.sup.1-7-2 and R.sup.1-7-3 together with the nitrogen atom they are attached to form a C.sub.3-C.sub.14 heterocycloalkyl optionally substituted by one, two or three R.sup.1-7-2-1; one or more methylenes in the C.sub.3-C.sub.14 heterocycloalkyl are optionally and independently substituted by oxygen atom, sulfur atom, sulfinyl, sulfonyl, carbonyl, vinylidene or —N(R.sup.1-7-2-2)—; R.sup.1-7-2-1 is independently C.sub.1-C.sub.7 alkyl or C.sub.3-C.sub.14 cycloalkyl; R.sup.1-7-2-2 is independently C.sub.1-C.sub.7 alkyl or C.sub.3-C.sub.14 cycloalkyl; R.sup.1-7-4 is independently halogen, hydroxyl, amino, mercapto, cyano, C.sub.1-C.sub.7 alkyl, C.sub.1-C.sub.7 alkoxy, C.sub.1-C.sub.7 alkylthio, C.sub.2-C.sub.7 alkenyl, C.sub.2-C.sub.7 alkynyl, C.sub.3-C.sub.14 cycloalkyl, C.sub.3-C.sub.14 heterocycloalkyl, C.sub.6-C.sub.10 aryl, C.sub.1-C.sub.7 heteroaryl or “amino substituted by one or two R.sup.1-7-4-1”; R.sup.1-7-4-1 is independently C.sub.1-C.sub.7 alkyl or C.sub.3-C.sub.14 cycloalkyl; R.sup.1-8 is independently oxo, halogen, —OH, amino, mercapto, cyano, C.sub.1-C.sub.7 alkyl, C.sub.1-C.sub.7 alkoxy, C.sub.1-C.sub.7 alkylthio, C.sub.2-C.sub.7 alkenyl, C.sub.2-C.sub.7 alkynyl, C.sub.3-C.sub.14 cycloalkyl, C.sub.3-C.sub.14 heterocycloalkyl, C.sub.6-C.sub.10 aryl, C.sub.1-C.sub.7 heteroaryl or “amino substituted by one or two R.sup.1-8-1”; R.sup.1-8-1 is independently C.sub.1-C.sub.7 alkyl or C.sub.3-C.sub.14 cycloalkyl; R.sup.1-9 is independently hydrogen or C.sub.1-C.sub.7 alkyl; R.sup.2 is —OR.sup.2-1, cyano, carboxyl; or “C.sub.2-C.sub.7 alkyl, C.sub.3-C.sub.14 cycloalkyl or C.sub.3-C.sub.14 heterocycloalkyl” optionally substituted by one, two or three R.sup.2-2; R.sup.2-1 is C.sub.1-C.sub.7 alkyl, C.sub.2-C.sub.7 alkenyl, C.sub.2-C.sub.7 alkynyl, C.sub.3-C.sub.14 cycloalkyl, C.sub.3-C.sub.14 heterocycloalkyl, C.sub.6-C.sub.10 aryl or C.sub.1-C.sub.7 heteroaryl; R.sup.2-2 is independently halogen, hydroxyl, amino, C.sub.1-C.sub.7 alkyl, C.sub.1-C.sub.7 alkoxy, C.sub.3-C.sub.14 cycloalkyl or C.sub.3-C.sub.14 heterocycloalkyl; in any one of the above cases, the heteroatoms in the C.sub.3-C.sub.14 heterocycloalkyl, C.sub.1-C.sub.7 heteroaryl are independently selected from one or more of boron, silicon, oxygen, sulfur, selenium, nitrogen and phosphorus; the number of heteroatoms is independently 1, 2, 3 or 4.

2. The pyrazolone-fused pyrimidine compound represented by formula II according to claim 1, the pharmaceutically acceptable salt thereof, the solvate thereof, the solvate of the pharmaceutically acceptable salt thereof, the metabolite thereof or the prodrug thereof, wherein, the compound is a pyrazolone-fused pyrimidine compound represented by formula I: ##STR00200## wherein, A is C.sub.3-C.sub.20 cycloalkyl substituted by one or two R.sup.1; R.sup.1 is independently halogen, —OR.sup.1-1, —SR.sup.1-2, —CN, —NR.sup.1-3R.sup.1-4, —C(═O)R.sup.1-5, —C(═NR.sup.1-6)R.sup.1-7 or “C.sub.2-C.sub.7 alkenyl, C.sub.2-C.sub.8 alkynyl, C.sub.3-C.sub.14 cycloalkyl, C.sub.3-C.sub.14 heterocycloalkyl, C.sub.6-C.sub.10 aryl or C.sub.1-C.sub.7 heteroaryl” optionally substituted by one, two or three R.sup.1-8; R.sup.1-1 is independently “C.sub.1-C.sub.7 alkyl, C.sub.2-C.sub.7 alkenyl, C.sub.2-C.sub.7 alkynyl, C.sub.3-C.sub.14 cycloalkyl, C.sub.3-C.sub.14 heterocycloalkyl, C.sub.6-C.sub.10 aryl, or C.sub.1-C.sub.7 heteroaryl” optionally substituted by one, two or three R.sup.1-1-1; R.sup.1-1-1 is independently halogen, hydroxyl, amino, mercapto, cyano, C.sub.1-C.sub.7 alkyl, C.sub.1-C.sub.7 alkoxy, C.sub.1-C.sub.7 alkylthio, C.sub.2-C.sub.7 alkenyl, C.sub.2-C.sub.7 alkynyl, C.sub.3-C.sub.14 cycloalkyl, C.sub.3-C.sub.14 heterocycloalkyl, C.sub.6-C.sub.10 aryl, C.sub.1-C.sub.7 heteroaryl or “amino substituted by one or two R.sup.1-1-1-1”; R.sup.1-1-1-1 is independently C.sub.1-C.sub.7 alkyl or C.sub.3-C.sub.14 cycloalkyl; R.sup.1-2 is independently hydrogen, or “C.sub.1-C.sub.7 alkyl, C.sub.2-C.sub.7 alkenyl, C.sub.2-C.sub.7 alkynyl, C.sub.3-C.sub.14 cycloalkyl, C.sub.3-C.sub.14 heterocycloalkyl, C.sub.6-C.sub.10 aryl, or C.sub.1-C.sub.7 heteroaryl” optionally substituted by one, two or three R.sup.1-2-1; R.sup.1-2-1 is independently hydrogen, halogen, hydroxyl, amino, mercapto, cyano, C.sub.1-C.sub.7 alkyl, C.sub.1-C.sub.7 alkoxy, C.sub.1-C.sub.7 alkylthio, C.sub.2-C.sub.7 alkenyl, C.sub.2-C.sub.7 alkynyl, C.sub.3-C.sub.14 cycloalkyl, C.sub.3-C.sub.14 heterocycloalkyl, C.sub.6-C.sub.10 aryl, C.sub.1-C.sub.7 heteroaryl or “amino substituted by one or two R.sup.1-2-1-1”; R.sup.1-2-1-1 is independently C.sub.1-C.sub.7 alkyl or C.sub.3-C.sub.14 cycloalkyl; R.sup.1-3 and R.sup.1-4 are independently hydrogen, —S(═O).sub.2R.sup.1-3-1, —C(═O)R.sup.1-3-2, —C(═NR.sup.1-3-3)NR.sup.1-3-5R.sup.1-3-6, —S(═O).sub.2NR.sup.1-3-7R.sup.1-3-8, —C(═O)NR.sup.1-3-9R.sup.1-3-10 or “C.sub.1-C.sub.7 alkyl, C.sub.2-C.sub.7 alkenyl, C.sub.2-C.sub.7 alkynyl, C.sub.3-C.sub.14 cycloalkyl, C.sub.3-C.sub.14 heterocycloalkyl, C.sub.6-C.sub.10 aryl or C.sub.1-C.sub.7 heteroaryl” optionally substituted by one, two or three R.sup.1-3-11; or, R.sup.1-3 and R.sup.1-4 together with the nitrogen atom they are attached to form a C.sub.3-C.sub.14 heterocycloalkyl optionally substituted by one, two or three R.sup.1-3-12; one or more methylenes in the C.sub.3-C.sub.14 heterocycloalkyl are optionally and independently substituted by oxygen atom, sulfur atom, sulfinyl, sulfonyl, carbonyl, vinylidene or —N(R.sup.1-3-13)—; R.sup.1-3-13 is independently C.sub.1-C.sub.7 alkyl or C.sub.3-C.sub.14 cycloalkyl; R.sup.1-3-1 and R.sup.1-3-2 are independently “C.sub.1-C.sub.7 alkyl, C.sub.2-C.sub.7 alkenyl, C.sub.2-C.sub.7 alkynyl, C.sub.3-C.sub.14 cycloalkyl, C.sub.3-C.sub.14 heterocycloalkyl or C.sub.6-C.sub.10 aryl” optionally substituted by one or two R.sup.1-3-1-1; R.sup.1-3-1-1 is independently C.sub.1-C.sub.7 alkyl or C.sub.3-C.sub.14 cycloalkyl; R.sup.1-3-3 is independently hydrogen, —CN, C.sub.1-C.sub.7 alkyl, C.sub.2-C.sub.7 alkenyl, C.sub.2-C.sub.7 alkynyl or C.sub.3-C.sub.14 cycloalkyl; R.sup.1-3-1, R.sup.1-3-6, R.sup.1-3-7, R.sup.1-3-8, R.sup.1-3-9 and R.sup.1-3-10 are independently C.sub.1-C.sub.7 alkyl, C.sub.2-C.sub.7 alkenyl, C.sub.2-C.sub.7 alkynyl or C.sub.3-C.sub.14 cycloalkyl; or, R.sup.1-3-5 and R.sup.1-3-6 together with the nitrogen atom they are attached to form a C.sub.3-C.sub.14 heterocycloalkyl optionally substituted by one, two or three R.sup.1-3-5-1; one or more methylenes in the C.sub.3-C.sub.14 heterocycloalkyl are optionally and independently substituted by oxygen atom, sulfur atom, sulfinyl, sulfonyl, carbonyl, vinylidene or —N(R.sup.1-3-5-2)—; R.sup.1-3-5-1 is independently C.sub.1-C.sub.7 alkyl or C.sub.3-C.sub.14 cycloalkyl; R.sup.1-3-5-2 is independently C.sub.1-C.sub.7 alkyl or C.sub.3-C.sub.14 cycloalkyl; or, R.sup.1-3-7 and R.sup.1-3-8 together with the nitrogen atom they are attached to form a C.sub.3-C.sub.14 heterocycloalkyl optionally substituted by one, two or three R.sup.1-3-7-1; one or more methylenes in the C.sub.3-C.sub.14 heterocycloalkyl are optionally and independently substituted by oxygen atom, sulfur atom, sulfinyl, sulfonyl, carbonyl, vinylidene or —N(R.sup.1-3-7-2)—; R.sup.1-3-7-1 is independently C.sub.1-C.sub.7 alkyl or C.sub.3-C.sub.14 cycloalkyl; R.sup.1-3-7-2 is independently C.sub.1-C.sub.7 alkyl or C.sub.3-C.sub.14 cycloalkyl; or, R.sup.1-3-9 and R.sup.1-3-10 together with the nitrogen atom they are attached to form a C.sub.3-C.sub.14 heterocycloalkyl optionally substituted by one, two or three R.sup.1-3-9-1; one or more methylenes in the C.sub.3-C.sub.14 heterocycloalkyl are optionally and independently substituted by oxygen atom, sulfur atom, sulfinyl, sulfonyl, carbonyl, vinylidene or —N(R.sup.1-3-9-2)—; R.sup.1-3-9-1 is independently C.sub.1-C.sub.7 alkyl or C.sub.3-C.sub.14 cycloalkyl; R.sup.1-3-9-2 is independently C.sub.1-C.sub.7 alkyl or C.sub.3-C.sub.14 cycloalkyl; R.sup.1-3-11 is independently halogen, hydroxyl, amino, mercapto, cyano, C.sub.1-C.sub.7 alkyl, C.sub.1-C.sub.7 alkoxy, C.sub.1-C.sub.7 alkylthio, C.sub.2-C.sub.7 alkenyl, C.sub.2-C.sub.7 alkynyl, C.sub.3-C.sub.14 cycloalkyl, C.sub.3-C.sub.14 heterocycloalkyl, C.sub.6-C.sub.10 aryl, C.sub.1-C.sub.7 heteroaryl or “amino substituted by one or two R.sup.1-3-11”; R.sup.1-3-11-1 is independently C.sub.1-C.sub.7 alkyl or C.sub.3-C.sub.14 cycloalkyl; R.sup.1-3-12 is independently halogen, hydroxyl, amino, mercapto, cyano, C.sub.1-C.sub.7 alkyl, C.sub.1-C.sub.7 alkoxy, C.sub.1-C.sub.7 alkylthio, C.sub.2-C.sub.7 alkenyl, C.sub.2-C.sub.7 alkynyl, C.sub.3-C.sub.14 cycloalkyl, C.sub.3-C.sub.14 heterocycloalkyl, C.sub.6-C.sub.10 aryl, C.sub.1-C.sub.7 heteroaryl or “amino substituted by one or two R.sup.1-3-12-1”; R.sup.1-3-12-1 is independently C.sub.1-C.sub.7 alkyl or C.sub.3-C.sub.14 cycloalkyl; R.sup.1-5 is independently hydrogen, —NR.sup.1-5-1R.sup.1-5-2, —OR.sup.1-5-3 or “C.sub.1-C.sub.7 alkyl, C.sub.2-C.sub.7 alkenyl, C.sub.2-C.sub.7 alkynyl, C.sub.3-C.sub.14 cycloalkyl, C.sub.3-C.sub.14 heterocycloalkyl, C.sub.6-C.sub.10 aryl, or C.sub.1-C.sub.7 heteroaryl” optionally substituted by one, two or three R.sup.1-5-4; R.sup.1-5-1 and R.sup.1-5-2 are independently hydrogen, C.sub.1-C.sub.7 alkyl, C.sub.2-C.sub.7 alkenyl, C.sub.2-C.sub.7 alkynyl or C.sub.3-C.sub.14 cycloalkyl; or, R.sup.1-5-1 and R.sup.1-5-2 together with the nitrogen atom they are attached to form a C.sub.3-C.sub.14 heterocycloalkyl optionally substituted by one, two or three R.sup.1-5-1-1; one or more methylenes in the C.sub.3-C.sub.14 heterocycloalkyl are optionally and independently substituted by oxygen atom, sulfur atom, sulfinyl, sulfonyl, carbonyl, vinylidene or —N(R.sup.1-5-1-2)—; R.sup.1-5-1-1 is independently C.sub.1-C.sub.7 alkyl or C.sub.3-C.sub.14 cycloalkyl; R.sup.1-5-1-2 is independently C.sub.1-C.sub.7 alkyl or C.sub.3-C.sub.14 cycloalkyl; R.sup.1-5-3 is independently hydrogen, C.sub.1-C.sub.7 alkyl, C.sub.2-C.sub.7 alkenyl, C.sub.2-C.sub.7 alkynyl, C.sub.3-C.sub.14 cycloalkyl, C.sub.3-C.sub.14 heterocycloalkyl, C.sub.6-C.sub.10 aryl or C.sub.1-C.sub.7 heteroaryl; R.sup.1-5-4 is independently halogen, hydroxyl, amino, mercapto, cyano, C.sub.1-C.sub.7 alkyl, C.sub.1-C.sub.7 alkoxy, C.sub.1-C.sub.7 alkylthio, C.sub.2-C.sub.7 alkenyl, C.sub.2-C.sub.7 alkynyl, C.sub.3-C.sub.14 cycloalkyl, C.sub.3-C.sub.14 heterocycloalkyl, C.sub.6-C.sub.10 aryl, C.sub.1-C.sub.7 heteroaryl or “amino substituted by one or two R.sup.1-5-4-1”; R.sup.1-5-4-1 is independently C.sub.1-C.sub.7 alkyl or C.sub.3-C.sub.14 cycloalkyl; R.sup.1-6 is independently hydrogen, —CN, —OH or “C.sub.1-C.sub.7 alkyl, C.sub.2-C.sub.7 alkenyl, C.sub.2-C.sub.7 alkynyl, C.sub.3-C.sub.14 cycloalkyl, C.sub.3-C.sub.14 heterocycloalkyl, C.sub.6-C.sub.10 aryl, or C.sub.1-C.sub.7 heteroaryl” optionally substituted by one, two or three R.sup.1-6-1; R.sup.1-6-1 is independently halogen, hydroxyl, amino, mercapto, cyano, C.sub.1-C.sub.7 alkyl, C.sub.1-C.sub.7 alkoxy, C.sub.1-C.sub.7 alkylthio, C.sub.2-C.sub.7 alkenyl, C.sub.2-C.sub.7 alkynyl, C.sub.3-C.sub.14 cycloalkyl, C.sub.3-C.sub.14 heterocycloalkyl, C.sub.6-C.sub.10 aryl, C.sub.1-C.sub.7 heteroaryl or “amino substituted by one or two R.sup.1-6-1-1”; R.sup.1-6-1-1 is independently C.sub.1-C.sub.7 alkyl or C.sub.3-C.sub.14 cycloalkyl; R.sup.1-7 is independently hydrogen, —OR.sup.1-7-1, —NR.sup.1-7-2R.sup.1-7-3 or “C.sub.1-C.sub.7 alkyl, C.sub.2-C.sub.7 alkenyl, C.sub.2-C.sub.7 alkynyl, C.sub.3-C.sub.14 cycloalkyl, C.sub.3-C.sub.14 heterocycloalkyl, C.sub.6-C.sub.10 aryl or C.sub.1-C.sub.7 heteroaryl” optionally substituted by one, two or three R.sup.1-7-4; R.sup.1-7-1 is independently hydrogen, C.sub.1-C.sub.7 alkyl, C.sub.2-C.sub.7 alkenyl, C.sub.2-C.sub.7 alkynyl, C.sub.3-C.sub.14 cycloalkyl, C.sub.3-C.sub.14 heterocycloalkyl, C.sub.6-C.sub.10 aryl or C.sub.1-C.sub.7 heteroaryl; R.sup.1-7-2 and R.sup.1-7-3 are independently C.sub.1-C.sub.7 alkyl, C.sub.2-C.sub.7 alkenyl, C.sub.2-C.sub.7 alkynyl or C.sub.3-C.sub.14 cycloalkyl; or, R.sup.1-7-2 and R.sup.1-7-3 together with the nitrogen atom they are attached to form a C.sub.3-C.sub.14 heterocycloalkyl optionally substituted by one, two or three R.sup.1-7-2-1; one or more methylenes in the C.sub.3-C.sub.14 heterocycloalkyl are optionally and independently substituted by oxygen atom, sulfur atom, sulfinyl, sulfonyl, carbonyl, vinylidene or —N(R.sup.1-7-2-2)—; R.sup.1-7-2-1 is independently C.sub.1-C.sub.7 alkyl or C.sub.3-C.sub.14 cycloalkyl; R.sup.1-7-2-2 is independently C.sub.1-C.sub.7 alkyl or C.sub.3-C.sub.14 cycloalkyl; R.sup.1-7-4 is independently halogen, hydroxyl, amino, mercapto, cyano, C.sub.1-C.sub.7 alkyl, C.sub.1-C.sub.7 alkoxy, C.sub.1-C.sub.7 alkylthio, C.sub.2-C.sub.7 alkenyl, C.sub.2-C.sub.7 alkynyl, C.sub.3-C.sub.14 cycloalkyl, C.sub.3-C.sub.14 heterocycloalkyl, C.sub.6-C.sub.10 aryl, C.sub.1-C.sub.7 heteroaryl or “amino substituted by one or two R.sup.1-7-4-1”; R.sup.1-7-4-1 is independently C.sub.1-C.sub.7 alkyl or C.sub.3-C.sub.14 cycloalkyl; R.sup.1-8 is independently halogen, —OH, amino, mercapto, cyano, C.sub.1-C.sub.7 alkyl, C.sub.1-C.sub.7 alkoxy, C.sub.1-C.sub.7 alkylthio, C.sub.2-C.sub.7 alkenyl, C.sub.2-C.sub.7 alkynyl, C.sub.3-C.sub.14 cycloalkyl, C.sub.3-C.sub.14 heterocycloalkyl, C.sub.6-C.sub.10 aryl, C.sub.1-C.sub.7 heteroaryl or “amino substituted by one or two R.sup.1-8-1”; R.sup.1-8-1 is independently C.sub.1-C.sub.7 alkyl or C.sub.3-C.sub.14 cycloalkyl; R.sup.2 is —OR.sup.2-1, cyano, carboxyl; or “C.sub.2-C.sub.7 alkyl, C.sub.3-C.sub.14 cycloalkyl or C.sub.3-C.sub.14 heterocycloalkyl” optionally substituted by one, two or three R.sup.2-2; R.sup.2-1 is C.sub.1-C.sub.7 alkyl, C.sub.2-C.sub.7 alkenyl, C.sub.2-C.sub.7 alkynyl, C.sub.3-C.sub.14 cycloalkyl, C.sub.3-C.sub.14 heterocycloalkyl, C.sub.6-C.sub.10 aryl or C.sub.1-C.sub.7 heteroaryl; R.sup.2-2 is independently halogen, hydroxyl, amino, C.sub.1-C.sub.7 alkyl, C.sub.1-C.sub.7 alkoxy, C.sub.3-C.sub.14 cycloalkyl or C.sub.3-C.sub.14 heterocycloalkyl; in any one of the above cases, the heteroatoms in the C.sub.3-C.sub.14 heterocycloalkyl, C.sub.1-C.sub.7 heteroaryl are independently selected from one or more of boron, silicon, oxygen, sulfur, selenium, nitrogen and phosphorus; the number of heteroatoms is independently 1, 2, 3 or 4.

3. The pyrazolone-fused pyrimidine compound represented by formula II according to claim 1, the pharmaceutically acceptable salt thereof, the solvate thereof, the solvate of the pharmaceutically acceptable salt thereof, the metabolite thereof or the prodrug thereof, wherein, when A is C.sub.3-C.sub.20 cycloalkyl substituted by one or two R.sup.1, the C.sub.3-C.sub.20 cycloalkyl is C.sub.3-C.sub.20 monocyclic cycloalkyl, C.sub.3-C.sub.20 spiro cycloalkyl, C.sub.3-C.sub.20 fused cycloalkyl or C.sub.3-C.sub.20 bridged cycloalkyl; or, when A is C.sub.3-C.sub.20 cycloalkyl substituted by one or two R.sup.1, the C.sub.3-C.sub.20 cycloalkyl is C.sub.3-C.sub.20 saturated cycloalkyl; or, when R.sup.1 is independently C.sub.3-C.sub.14 heterocycloalkyl, the C.sub.3-C.sub.14 heterocycloalkyl is C.sub.3-C.sub.14 monocyclic heterocycloalkyl, C.sub.3-C.sub.14 spiro heterocycloalkyl, C.sub.3-C.sub.14 fused heterocycloalkyl or C.sub.3-C.sub.14 bridged heterocycloalkyl; or, when R.sup.1 is independently C.sub.3-C.sub.14 heterocycloalkyl, the heteroatom of the C.sub.3-C.sub.14 heterocycloalkyl is not substituted; or, when R.sup.1 is independently C.sub.3-C.sub.14 heterocycloalkyl, the methylene in the C.sub.3-C.sub.14 heterocycloalkyl is not substituted; or, when R.sup.1 is independently C.sub.3-C.sub.14 heterocycloalkyl substituted by one R.sup.1-8, the C.sub.3-C.sub.14 heterocycloalkyl is C.sub.3-C.sub.14 monocyclic heterocycloalkyl, C.sub.3-C.sub.14 spiro heterocycloalkyl, C.sub.3-C.sub.14 fused heterocycloalkyl or C.sub.3-C.sub.14 bridged heterocycloalkyl; or, when R.sup.1 is independently C.sub.3-C.sub.14 heterocycloalkyl substituted by one R.sup.1-8, the heteroatom of the C.sub.3-C.sub.14 heterocycloalkyl is not substituted except R.sup.1-8; or, when R.sup.1 is independently C.sub.3-C.sub.14 heterocycloalkyl substituted by one R.sup.1-8, the methylene in the C.sub.3-C.sub.14 heterocycloalkyl is not substituted; or, when R.sup.1-3 and R.sup.1-4 are independently C.sub.1-C.sub.7 alkyl, the C.sub.1-C.sub.7 alkyl is C.sub.1-C.sub.3 alkyl; or, when R.sup.1-3-1 is independently C.sub.1-C.sub.7 alkyl, the C.sub.1-C.sub.7 alkyl is C.sub.1-C.sub.3 alkyl; or, when R.sup.1-3-2 is independently C.sub.3-C.sub.14 cycloalkyl, the C.sub.3-C.sub.14 cycloalkyl is C.sub.3-C.sub.14 monocyclic cycloalkyl, C.sub.3-C.sub.14 spiro cycloalkyl, C.sub.3-C.sub.14 fused cycloalkyl or C.sub.3-C.sub.14 bridged cycloalkyl; or, when R.sup.1-3-2 is C.sub.3-C.sub.14 cycloalkyl, the C.sub.3-C.sub.14 cycloalkyl is C.sub.3-C.sub.14 saturated cycloalkyl; or, when R.sup.1-5 is independently C.sub.3-C.sub.14 heterocycloalkyl, the C.sub.3-C.sub.14 heterocycloalkyl is C.sub.3-C.sub.14 monocyclic heterocycloalkyl, C.sub.3-C.sub.14 spiro heterocycloalkyl, C.sub.3-C.sub.14 fused heterocycloalkyl or C.sub.3-C.sub.14 bridged heterocycloalkyl; or, when R.sup.1-5 is independently C.sub.3-C.sub.14 heterocycloalkyl, the heteroatom of the C.sub.3-C.sub.14 heterocycloalkyl is not substituted; or, when R.sup.1-5 is independently C.sub.3-C.sub.14 heterocycloalkyl, the methylene in the C.sub.3-C.sub.14 heterocycloalkyl is not substituted; or, when R.sup.1-5-1 and R.sup.1-5-2 are independently C.sub.1-C.sub.7 alkyl, the C.sub.1-C.sub.7 alkyl is C.sub.1-C.sub.3 alkyl; or, when R.sup.1-5-1 and R.sup.1-5-2 are independently C.sub.3-C.sub.14 cycloalkyl, the C.sub.3-C.sub.14 cycloalkyl is C.sub.3-C.sub.14 monocyclic cycloalkyl, C.sub.3-C.sub.14 spiro cycloalkyl, C.sub.3-C.sub.14 fused cycloalkyl or C.sub.3-C.sub.14 bridged cycloalkyl; or, when R.sup.1-5-1 and R.sup.1-5-2 are independently C.sub.3-C.sub.14 cycloalkyl, the C.sub.3-C.sub.14 cycloalkyl is C.sub.3-C.sub.14 saturated cycloalkyl; or, when R.sup.1-5-3 is independently C.sub.1-C.sub.7 alkyl, the C.sub.1-C.sub.7 alkyl is C.sub.1-C.sub.3 alkyl; or, when R.sup.1-9 is independently C.sub.1-C.sub.7 alkyl, the C.sub.1-C.sub.7 alkyl is C.sub.1-C.sub.3 alkyl; or, when R.sup.2 is C.sub.2-C.sub.7 alkyl optionally substituted by one, two or three R.sup.2-2, the C.sub.2-C.sub.7 alkyl is C.sub.2-C.sub.4 alkyl; or, when R.sup.2 is C.sub.3-C.sub.14 heterocycloalkyl optionally substituted by one, two or three R.sup.2-2, the C.sub.3-C.sub.14 heterocycloalkyl is C.sub.3-C.sub.14 monocyclic heterocycloalkyl, C.sub.3-C.sub.14 spiro heterocycloalkyl, C.sub.3-C.sub.14 fused heterocycloalkyl or C.sub.3-C.sub.14 bridged heterocycloalkyl; or, when R.sup.2 is C.sub.3-C.sub.14 heterocycloalkyl optionally substituted by one, two or three R.sup.2-2, the heteroatom of the C.sub.3-C.sub.14 heterocycloalkyl is not substituted except R.sup.2-2; or, when R.sup.2 is C.sub.3-C.sub.14 heterocycloalkyl optionally substituted by one, two or three R.sup.2-2, the methylene in the C.sub.3-C.sub.14 heterocycloalkyl is not substituted; or, the ratio of each isomer in the pyrazolone-fused pyrimidine compound represented by formula II is equal; or, the atoms in the pyrazolone-fused pyrimidine compound represented by formula II, the pharmaceutically acceptable salt thereof, the solvate thereof, the solvate of the pharmaceutically acceptable salt thereof, the metabolite thereof or the prodrug thereof all exist in their natural abundance.

4. The pyrazolone-fused pyrimidine compound represented by formula II according to claim 3, the pharmaceutically acceptable salt thereof, the solvate thereof, the solvate of the pharmaceutically acceptable salt thereof, the metabolite thereof or the prodrug thereof, wherein, when A is C.sub.3-C.sub.20 cycloalkyl substituted by one or two R.sup.1, the C.sub.3-C.sub.20 cycloalkyl is C.sub.3-C.sub.20 monocyclic cycloalkyl, C.sub.3-C.sub.20 monocyclic cycloalkyl is C.sub.3-C.sub.6 monocyclic cycloalkyl; or, when A is C.sub.3-C.sub.20 cycloalkyl substituted by one or two R.sup.1, the C.sub.3-C.sub.20 cycloalkyl is C.sub.3-C.sub.20 bridged cycloalkyl; the C.sub.3-C.sub.20 bridged cycloalkyl is C.sub.5-C.sub.8 bridged cycloalkyl; or, when R.sup.1 is independently C.sub.3-C.sub.14 heterocycloalkyl, the C.sub.3-C.sub.14 heterocycloalkyl is C.sub.3-C.sub.14 monocyclic heterocycloalkyl; the C.sub.3-C.sub.14 monocyclic heterocycloalkyl is “C.sub.3-C.sub.9 monocyclic heterocycloalkyl having one or two heteroatoms selected from one or two of N, O and S”; or, when R.sup.1 is independently C.sub.3-C.sub.14 heterocycloalkyl substituted by one R.sup.1-8, the C.sub.3-C.sub.14 heterocycloalkyl is C.sub.3-C.sub.14 monocyclic heterocycloalkyl; the C.sub.3-C.sub.14 monocyclic heterocycloalkyl is the “C.sub.3-C.sub.9 monocyclic heterocycloalkyl having one or two heteroatoms selected from one or two of N, O and S”; or, when R.sup.1-3 and R.sup.1-4 are independently C.sub.1-C.sub.7 alkyl, the C.sub.1-C.sub.7 alkyl is methyl, ethyl, n-propyl or isopropyl; or, when R.sup.1-3-1 is independently C.sub.1-C.sub.7 alkyl, the C.sub.1-C.sub.7 alkyl is methyl, ethyl, n-propyl or isopropyl; or, when R.sup.1-3-2 is independently C.sub.3-C.sub.14 cycloalkyl, the C.sub.3-C.sub.14 cycloalkyl is C.sub.3-C.sub.14 monocyclic cycloalkyl; the C.sub.3-C.sub.14 monocyclic cycloalkyl is C.sub.3-C.sub.6 monocyclic cycloalkyl; or, when R.sup.1-5 is independently C.sub.3-C.sub.14 heterocycloalkyl, the C.sub.3-C.sub.14 heterocycloalkyl is C.sub.3-C.sub.14 monocyclic heterocycloalkyl; the C.sub.3-C.sub.14 monocyclic heterocycloalkyl is “C.sub.3-C.sub.9 monocyclic heterocycloalkyl having one or two heteroatoms selected from one or two of N, O and S”; or, when R.sup.1-5-1 and R.sup.1-5-2 are independently C.sub.1-C.sub.7 alkyl, the C.sub.1-C.sub.7 alkyl is methyl, ethyl, n-propyl or isopropyl; or, when R.sup.1-5-1 and R.sup.1-5-2 are independently C.sub.3-C.sub.14 cycloalkyl, the C.sub.3-C.sub.14 cycloalkyl is C.sub.3-C.sub.14 monocyclic cycloalkyl; the C.sub.3-C.sub.14 monocyclic cycloalkyl is C.sub.3-C.sub.6 monocyclic cycloalkyl; or, when R.sup.1-5-3 is independently C.sub.1-C.sub.7 alkyl, the C.sub.1-C.sub.7 alkyl is methyl, ethyl, n-propyl or isopropyl; or, when R.sup.2 is C.sub.2-C.sub.7 alkyl optionally substituted by one, two or three R.sup.2-2, the C.sub.2-C.sub.7 alkyl is ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl; or, when R.sup.2 is independently C.sub.3-C.sub.14 heterocycloalkyl substituted by one, two or three R.sup.2-2, the C.sub.3-C.sub.14 heterocycloalkyl is C.sub.3-C.sub.14 monocyclic heterocycloalkyl; the C.sub.3-C.sub.14 monocyclic heterocycloalkyl is “C.sub.3-C.sub.9 monocyclic heterocycloalkyl having one or two heteroatoms selected from one or two of N, O and S”; or, the ratio of each isomer in the pyrazolone-fused pyrimidine compound represented by formula I is equal; or, the atoms in the pyrazolone-fused pyrimidine compound represented by formula I, the pharmaceutically acceptable salt thereof, the solvate thereof, the solvate of the pharmaceutically acceptable salt thereof, the metabolite thereof or the prodrug thereof all exist in their natural abundance.

5. The pyrazolone-fused pyrimidine compound represented by formula II according to claim 4, the pharmaceutically acceptable salt thereof, the solvate thereof, the solvate of the pharmaceutically acceptable salt thereof, the metabolite thereof or the prodrug thereof, wherein, when A is C.sub.3-C.sub.20 cycloalkyl substituted by one or two R.sup.1, the C.sub.3-C.sub.20 cycloalkyl is C.sub.3-C.sub.20 monocyclic cycloalkyl, the C.sub.3-C.sub.20 monocyclic cycloalkyl is cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; or, when A is C.sub.3-C.sub.20 cycloalkyl substituted by one or two R.sup.1, the C.sub.3-C.sub.20 cycloalkyl is C.sub.3-C.sub.20 bridged cycloalkyl; the C.sub.3-C.sub.20 bridged cycloalkyl is ##STR00201## or, when R.sup.1 is independently C.sub.3-C.sub.14 heterocycloalkyl, the C.sub.3-C.sub.14 heterocycloalkyl is C.sub.3-C.sub.14 monocyclic heterocycloalkyl; the C.sub.3-C.sub.14 monocyclic heterocycloalkyl is ##STR00202## or, when R.sup.1 is independently C.sub.3-C.sub.14 heterocycloalkyl substituted by one R.sup.1-8, the C.sub.3-C.sub.14 heterocycloalkyl substituted by one R.sup.1-8 is; ##STR00203## or, when R.sup.1-3-2 is C.sub.3-C.sub.14 cycloalkyl, the C.sub.3-C.sub.14 cycloalkyl is C.sub.3-C.sub.14 monocyclic cycloalkyl; the C.sub.3-C.sub.14 monocyclic cycloalkyl is cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; or, when R.sup.1-5 is independently C.sub.3-C.sub.14 heterocycloalkyl, the C.sub.3-C.sub.14 heterocycloalkyl is C.sub.3-C.sub.14 monocyclic heterocycloalkyl; the C.sub.3-C.sub.14 monocyclic heterocycloalkyl is ##STR00204## or, when R.sup.1-5-1 and R.sup.1-5-2 are independently C.sub.3-C.sub.14 cycloalkyl, the C.sub.3-C.sub.14 cycloalkyl is C.sub.3-C.sub.14 monocyclic cycloalkyl; the C.sub.3-C.sub.14 monocyclic cycloalkyl is cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; or, when R.sup.2 is C.sub.3-C.sub.14 heterocycloalkyl optionally substituted by one, two or three R.sup.2-2, the C.sub.3-C.sub.14 heterocycloalkyl is C.sub.3-C.sub.14 monocyclic heterocycloalkyl; the C.sub.3-C.sub.14 monocyclic heterocycloalkyl is oxetan-3-yl.

6. The pyrazolone-fused pyrimidine compound represented by formula II according to claim 1, the pharmaceutically acceptable salt thereof, the solvate thereof, the solvate of the pharmaceutically acceptable salt thereof, the metabolite thereof or the prodrug thereof, wherein, when A is C.sub.3-C.sub.20 cycloalkyl substituted by one R.sup.1, the A is ##STR00205## or, when R.sup.1 is independently C.sub.3-C.sub.14 heterocycloalkyl, the C.sub.3-C.sub.14 heterocycloalkyl is C.sub.3-C.sub.14 monocyclic heterocycloalkyl; the C.sub.3-C.sub.14 monocyclic heterocycloalkyl is ##STR00206## or, when R.sup.1-5 is independently C.sub.3-C.sub.14 heterocycloalkyl, the C.sub.3-C.sub.14 heterocycloalkyl is C.sub.3-C.sub.14 monocyclic heterocycloalkyl; the C.sub.3-C.sub.14 monocyclic heterocycloalkyl ##STR00207## or, when R.sup.2 is C.sub.2-C.sub.7 alkyl substituted by one R.sup.2-2, R.sup.2-2 is hydroxyl; the C.sub.2-C.sub.7 alkyl substituted by one R.sup.2-2 is ##STR00208## or, when R.sup.2 is C.sub.3-C.sub.14 heterocycloalkyl substituted by one R.sup.2-2, R.sup.2-2 is halogen or hydroxyl; the C.sub.3-C.sub.14 heterocycloalkyl substituted by one R.sup.2-2 is ##STR00209##

7. The pyrazolone-fused pyrimidine compound represented by formula II according to claim 6, the pharmaceutically acceptable salt thereof, the solvate thereof, the solvate of the pharmaceutically acceptable salt thereof, the metabolite thereof or the prodrug thereof, wherein, when A is C.sub.3-C.sub.20 cycloalkyl substituted by one R.sup.1; the A is ##STR00210##

8. The pyrazolone-fused pyrimidine compound represented by formula II according to claim 1, the pharmaceutically acceptable salt thereof, the solvate thereof, the solvate of the pharmaceutically acceptable salt thereof, the metabolite thereof or the prodrug thereof, wherein, A is C.sub.3-C.sub.20 cycloalkyl substituted by one R.sup.1; or, X is N; or, R.sup.1 is independently cyano, halogen, —NR.sup.1-3R.sup.1-4, —C(═O)R.sup.1-5, —C(═NR.sup.1-6)R.sup.1-7, ═N—O—R.sup.1-9, C.sub.1-C.sub.7 heteroaryl or “C.sub.3-C.sub.14 heterocycloalkyl” optionally substituted by one R.sup.1-8; or, R.sup.1-3 and R.sup.1-4 are independently hydrogen, —S(═O).sub.2R.sup.1-3-1, —C(═O)R.sup.1-3-2, —C(═NR.sup.1-3-3)NR.sup.1-3-5R.sup.1-3-6, or C.sub.1-C.sub.7 alkyl; R.sup.1-3-1 and R.sup.1-3-2 are independently C.sub.1-C.sub.7 alkyl or C.sub.3-C.sub.14 cycloalkyl; R.sup.1-3-3 is hydrogen; R.sup.1-3-5 and R.sup.1-3-6 are hydrogen; or, R.sup.1-5 is independently —NR.sup.1-5-1R.sup.1-5-2, —OR.sup.1-5-3 or C.sub.3-C.sub.14 heterocycloalkyl; R.sup.1-5-1 and R.sup.1-5-2 are independently hydrogen, C.sub.1-C.sub.7 alkyl or C.sub.3-C.sub.14 cycloalkyl; R.sup.1-5-3 is independently hydrogen or C.sub.1-C.sub.7 alkyl; or, R.sup.1-8 is independently oxo; or, R.sup.2 is “C.sub.2-C.sub.7 alkyl, C.sub.3-C.sub.14 cycloalkyl or C.sub.3-C.sub.14 heterocycloalkyl” optionally substituted by one, two or three R.sup.2-2; R.sup.2-2 is independently halogen or hydroxyl.

9. The pyrazolone-fused pyrimidine compound represented by formula II according to claim 1, the pharmaceutically acceptable salt thereof, the solvate thereof, the solvate of the pharmaceutically acceptable salt thereof, the metabolite thereof or the prodrug thereof, wherein, A is C.sub.3-C.sub.20 cycloalkyl substituted by one R.sup.1; or, R.sup.1 is independently cyano, halogen, —NR.sup.1-3R.sup.1-4, —C(═O)R.sup.1-5, —C(═NR.sup.1-6)R.sup.1-7, C.sub.1-C.sub.7 heteroaryl or C.sub.3-C.sub.14 heterocycloalkyl; or, R.sup.1-3 and R.sup.1-4 are independently hydrogen, —S(═O).sub.2R.sup.1-3-1 or C.sub.1-C.sub.7 alkyl; R.sup.1-3-1 is independently C.sub.1-C.sub.7 alkyl; or, R.sup.1-5 is independently —NR.sup.1-5-1R.sup.1-5-2, —OR.sup.1-5-3 or C.sub.3-C.sub.14 heterocycloalkyl; R.sup.1-5-1 and R.sup.1-5-2 are independently hydrogen, C.sub.1-C.sub.7 alkyl or C.sub.3-C.sub.14 cycloalkyl; R.sup.1-5-3 is independently hydrogen or C.sub.1-C.sub.7 alkyl; or, R.sup.2 is “C.sub.2-C.sub.7 alkyl, C.sub.3-C.sub.14 cycloalkyl or C.sub.3-C.sub.14 heterocycloalkyl” optionally substituted by one, two or three R.sup.2-2; R.sup.2-2 is independently halogen or hydroxyl.

10. The pyrazolone-fused pyrimidine compound represented by formula II according to claim 9, the pharmaceutically acceptable salt thereof, the solvate thereof, the solvate of the pharmaceutically acceptable salt thereof, the metabolite thereof or the prodrug thereof, wherein, R.sup.1 is independently —NR.sup.1-3R.sup.1-4, —C(═O)R.sup.1-5 or C.sub.3-C.sub.14 heterocycloalkyl; or, R.sup.1-5 is independently —NR.sup.1-5-1R.sup.1-5-2, —OR.sup.1-5-3 or C.sub.3-C.sub.14 heterocycloalkyl; R.sup.1-5-1 and R.sup.1-5-2 are independently hydrogen, C.sub.1-C.sub.7 alkyl or C.sub.3-C.sub.14 cycloalkyl; R.sup.1-5-3 is hydrogen; or, R.sup.2 is “C.sub.2-C.sub.7 alkyl or C.sub.3-C.sub.14 heterocycloalkyl substituted by one R.sup.2-2”; R.sup.2-2 is halogen or hydroxyl.

11. The pyrazolone-fused pyrimidine compound represented by formula II according to claim 1, the pharmaceutically acceptable salt thereof, the solvate thereof, the solvate of the pharmaceutically acceptable salt thereof, the metabolite thereof or the prodrug thereof, wherein, the pyrazolone-fused pyrimidine compound represented by formula II is any of the following schemes: scheme (1): ##STR00211## A is ##STR00212## substituted by one or two R.sup.1; R.sup.1 is independently halogen, —CN, —NR.sup.1-3R.sup.1-4, —C(═O)R.sup.1-5, —C(═NR.sup.1-6)R.sup.1-7 or “C.sub.3-C.sub.14 cycloalkyl, C.sub.3-C.sub.14 heterocycloalkyl, C.sub.6-C.sub.10 aryl, or C.sub.1-C.sub.7 heteroaryl” optionally substituted by one, two or three R.sup.1-8; R.sup.1-3 and R.sup.1-4 are independently hydrogen, —S(═O).sub.2R.sup.1-3-1, —C(═O)R.sup.1-3-2, —C(═NR.sup.1-3-3)NR.sup.1-3-5R.sup.1-3-6, —S(═O).sub.2NR.sup.1-3-7R.sup.1-3-8, —C(═O)NR.sup.1-3-9R.sup.1-3-10 or “C.sub.1-C.sub.7 alkyl, C.sub.3-C.sub.14 cycloalkyl, C.sub.3-C.sub.14 heterocycloalkyl, C.sub.6-C.sub.10 aryl or C.sub.1-C.sub.7 heteroaryl” optionally substituted by one, two or three R.sup.1-3-11; R.sup.1-3-1 and R.sup.1-3-2 are independently “C.sub.1-C.sub.7 alkyl, C.sub.3-C.sub.14 cycloalkyl, C.sub.3-C.sub.14 heterocycloalkyl or C.sub.6-C.sub.10 aryl” optionally substituted by one or two R.sup.1-3-1-1; R.sup.1-3-1-1 is independently C.sub.1-C.sub.7 alkyl; R.sup.1-3-3 is independently hydrogen; R.sup.1-3-5, R.sup.1-3-6, R.sup.1-3-7, R.sup.1-3-8, R.sup.1-3-9 and R.sup.1-3-10 are independently C.sub.1-C.sub.7 alkyl or C.sub.3-C.sub.14 cycloalkyl; R.sup.1-3-11 is independently halogen, hydroxyl, amino, mercapto, cyano, C.sub.1-C.sub.7 alkyl, C.sub.1-C.sub.7 alkoxy, C.sub.1-C.sub.7 alkylthio, C.sub.3-C.sub.14 cycloalkyl, C.sub.3-C.sub.14 heterocycloalkyl, C.sub.6-C.sub.10 aryl, C.sub.1-C.sub.7 heteroaryl or “amino substituted by one or two R.sup.1-3-11”; R.sup.1-3-11-1 is independently C.sub.1-C.sub.7 alkyl or C.sub.3-C.sub.14 cycloalkyl; R.sup.1-5 is independently hydrogen, —NR.sup.1-5-1R.sup.1-5-2, —OR.sup.1-5-3 or “C.sub.1-C.sub.7 alkyl, C.sub.3-C.sub.14 cycloalkyl, C.sub.3-C.sub.14 heterocycloalkyl, C.sub.6-C.sub.10 aryl or C.sub.1-C.sub.7 heteroaryl” optionally substituted by one, two or three R.sup.1-5-4; R.sup.1-5-1 and R.sup.1-5-2 are independently hydrogen, C.sub.1-C.sub.7 alkyl or C.sub.3-C.sub.14 cycloalkyl; R.sup.1-5-3 is independently hydrogen, C.sub.1-C.sub.7 alkyl, C.sub.3-C.sub.14 cycloalkyl, C.sub.3-C.sub.14 heterocycloalkyl, C.sub.6-C.sub.10 aryl or C.sub.1-C.sub.7 heteroaryl; R.sup.1-5-4 is independently halogen, hydroxyl, amino, mercapto, cyano, C.sub.1-C.sub.7 alkyl, C.sub.1-C.sub.7 alkoxy, C.sub.1-C.sub.7 alkylthio, C.sub.3-C.sub.14 cycloalkyl, C.sub.3-C.sub.14 heterocycloalkyl, C.sub.6-C.sub.10 aryl, C.sub.1-C.sub.7 heteroaryl or “amino substituted by one or two R.sup.1-5-4-1”; R.sup.1-5-4-1 is independently C.sub.1-C.sub.7 alkyl or C.sub.3-C.sub.14 cycloalkyl; R.sup.1-6 is independently hydrogen, —CN, —OH; R.sup.1-7 is independently hydrogen, —NR.sup.1-7-2R.sup.1-7-3; R.sup.1-7-2 and R.sup.1-7-3 are independently C.sub.1-C.sub.7 alkyl or C.sub.3-C.sub.14 cycloalkyl; or, R.sup.1-7-2 and R.sup.1-7-3 together with the nitrogen atom they are attached to form a C.sub.3-C.sub.14 heterocycloalkyl optionally substituted by one, two or three R.sup.1-7-2-1; one or more methylenes in the C.sub.3-C.sub.14 heterocycloalkyl are optionally and independently substituted by oxygen atom, sulfur atom; R.sup.1-7-2-1 is independently C.sub.1-C.sub.7 alkyl or C.sub.3-C.sub.14 cycloalkyl; R.sup.1-8 is independently halogen, —OH, amino, mercapto, cyano, C.sub.1-C.sub.7 alkyl, C.sub.1-C.sub.7 alkoxy, C.sub.1-C.sub.7 alkylthio, C.sub.3-C.sub.14 cycloalkyl, C.sub.3-C.sub.14 heterocycloalkyl, C.sub.6-C.sub.10 aryl, C.sub.1-C.sub.7 heteroaryl or “amino substituted by one or two R.sup.1-8-1”; R.sup.1-8-1 is independently C.sub.1-C.sub.7 alkyl or C.sub.3-C.sub.14 cycloalkyl; R.sup.2 is “C.sub.2-C.sub.7 alkyl, C.sub.3-C.sub.14 cycloalkyl or C.sub.3-C.sub.14 heterocycloalkyl” optionally substituted by one, two or three R.sup.2-2; R.sup.2-2 is independently halogen or hydroxyl; in any one of the above cases, the heteroatoms in the C.sub.3-C.sub.14 heterocycloalkyl, C.sub.1-C.sub.7 heteroaryl are independently selected from one or more of boron, silicon, oxygen, sulfur, selenium, nitrogen and phosphorus; the number of heteroatoms is independently 1, 2, 3 or 4; scheme (2): ##STR00213## A is C.sub.3-C.sub.20 cycloalkyl substituted by one or two R.sup.1; R.sup.1 is independently cyano, halogen, —NR.sup.1-3R.sup.1-4, —C(═O)R.sup.1-5, —C(═NR.sup.1-6)R.sup.1-7, C.sub.1-C.sub.7 heteroaryl or C.sub.3-C.sub.14 heterocycloalkyl; R.sup.1-3 and R.sup.1-4 are independently hydrogen, —S(═O).sub.2R.sup.1-3-1 or C.sub.1-C.sub.7 alkyl; R.sup.1-3-1 is independently C.sub.1-C.sub.7 alkyl; R.sup.1-5 is independently —NR.sup.1-5-1R.sup.1-5-2, —OR.sup.1-5-3 or C.sub.3-C.sub.14 heterocycloalkyl; R.sup.1-5-1 and R.sup.1-5-2 are independently hydrogen, C.sub.1-C.sub.7 alkyl or C.sub.3-C.sub.14 cycloalkyl; R.sup.1-5-3 is independently hydrogen or C.sub.1-C.sub.7 alkyl; R.sup.2 is “C.sub.2-C.sub.7 alkyl or C.sub.3-C.sub.14 heterocycloalkyl substituted by one R.sup.2-2”; R.sup.2-2 is halogen or hydroxyl; scheme (3): ##STR00214## A is C.sub.3-C.sub.20 cycloalkyl substituted by one R.sup.1; R.sup.1 is —NR.sup.1-3R.sup.1-4, —C(═O)R.sup.1-5 or C.sub.3-C.sub.14 heterocycloalkyl; R.sup.1-3 and R.sup.1-4 are independently hydrogen, —S(═O).sub.2R.sup.1-3-1 or C.sub.1-C.sub.7 alkyl; R.sup.1-3-1 is independently C.sub.1-C.sub.7 alkyl; R.sup.1-5 is —NR.sup.1-5-1R.sup.1-5-2, —OR.sup.1-5-3 or C.sub.3-C.sub.14 heterocycloalkyl; R.sup.1-5-1 and R.sup.1-5-2 are independently hydrogen, C.sub.1-C.sub.7 alkyl or C.sub.3-C.sub.14 cycloalkyl; R.sup.1-5-3 is hydrogen or C.sub.1-C.sub.7 alkyl; R.sup.2 is “C.sub.2-C.sub.7 alkyl or C.sub.3-C.sub.14 heterocycloalkyl substituted by one R.sup.2-2”; R.sup.2-2 is hydroxyl; scheme (4): ##STR00215## A is C.sub.3-C.sub.20 cycloalkyl substituted by one R.sup.1; R.sup.1 is —NR.sup.1-3R.sup.1-4, —C(═O)R.sup.1-5 or C.sub.3-C.sub.14 heterocycloalkyl; R.sup.1-3 and R.sup.1-4 are independently hydrogen, —S(═O).sub.2R.sup.1-3-1 or C.sub.1-C.sub.7 alkyl; R.sup.1-3-1 is independently C.sub.1-C.sub.7 alkyl; R.sup.1-5 is —NR.sup.1-5-1R.sup.1-5-2, —OR.sup.1-5-3 or C.sub.3-C.sub.14 heterocycloalkyl; R.sup.1-5-1 and R.sup.1-5-2 are independently hydrogen, C.sub.1-C.sub.7 alkyl or C.sub.3-C.sub.14 cycloalkyl; R.sup.1-5-3 is hydrogen; R.sup.2 is “C.sub.2-C.sub.7 alkyl or C.sub.3-C.sub.14 heterocycloalkyl substituted by one R.sup.2-2”; R.sup.2-2 is hydroxyl; scheme (5): ##STR00216## A is ##STR00217## R.sup.1 is —NR.sup.1-3R.sup.1-4, —C(═O)R.sup.1-5 or C.sub.3-C.sub.14 heterocycloalkyl; R.sup.1-3 and R.sup.1-4 are independently hydrogen, —S(═O).sub.2R.sup.1-3-1 or C.sub.1-C.sub.7 alkyl; R.sup.1-3-1 is independently C.sub.1-C.sub.7 alkyl; R.sup.1-5 is —NR.sup.1-5-1R.sup.1-5-2, —OR.sup.1-5-3 or C.sub.3-C.sub.14 heterocycloalkyl; R.sup.1-5-1 and R.sup.1-5-2 are independently hydrogen, C.sub.1-C.sub.7 alkyl or C.sub.3-C.sub.14 cycloalkyl; R.sup.1-5-3 is hydrogen or C.sub.1-C.sub.7 alkyl; R.sup.2 is “C.sub.2-C.sub.7 alkyl or C.sub.3-C.sub.14 heterocycloalkyl substituted by one R.sup.2-2”; R.sup.2-2 is hydroxyl; scheme (6): ##STR00218## A is ##STR00219## R.sup.1 is —NR.sup.1-3R.sup.1-4, —C(═O)R.sup.1-5 or C.sub.3-C.sub.14 heterocycloalkyl; R.sup.1-3 and R.sup.1-4 are independently hydrogen, —S(═O).sub.2R.sup.1-3-1 or C.sub.1-C.sub.7 alkyl; R.sup.1-3-1 is independently C.sub.1-C.sub.7 alkyl; R.sup.1-5 is —NR.sup.1-5-1R.sup.1-5-2, —OR.sup.1-5-3 or C.sub.3-C.sub.14 heterocycloalkyl; R.sup.1-5-1 and R.sup.1-5-2 are independently hydrogen, C.sub.1-C.sub.7 alkyl or C.sub.3-C.sub.14 cycloalkyl; R.sup.1-5-3 is hydrogen or C.sub.1-C.sub.7 alkyl; R.sup.2 is ##STR00220## scheme (7): A is ##STR00221## substituted by one or two R.sup.1; X is CH or N; R.sup.1 is independently halogen, —CN, —NR.sup.1-3R.sup.1-4, —C(═O)R.sup.1-5, —C(═NR.sup.1-6)R.sup.1-7, ═N—O—R.sup.1-9 or “C.sub.3-C.sub.14 cycloalkyl, C.sub.3-C.sub.14 heterocycloalkyl, C.sub.6-C.sub.10 aryl, or C.sub.1-C.sub.7 heteroaryl” optionally substituted by one, two or three R.sup.1-8; R.sup.1-3 and R.sup.1-4 are independently hydrogen, —S(═O).sub.2R.sup.1-3-1, —C(═O)R.sup.1-3-2, —C(═NR.sup.1-3-3)NR.sup.1-3-5R.sup.1-3-6, —S(═O).sub.2NR.sup.1-3-7R.sup.1-3-8, —C(═O)NR.sup.1-3-9R.sup.1-3-10 or “C.sub.1-C.sub.7 alkyl, C.sub.3-C.sub.14 cycloalkyl, C.sub.3-C.sub.14 heterocycloalkyl, C.sub.6-C.sub.10 aryl or C.sub.1-C.sub.7 heteroaryl” optionally substituted by one, two or three R.sup.1-3-11; R.sup.1-3-1 and R.sup.1-3-2 are independently “C.sub.1-C.sub.7 alkyl, C.sub.3-C.sub.14 cycloalkyl, C.sub.3-C.sub.14 heterocycloalkyl or C.sub.6-C.sub.10 aryl optionally substituted” by one or two R.sup.1-3-1-1; R.sup.1-3-1-1 is independently C.sub.1-C.sub.7 alkyl; R.sup.1-3-3 is independently hydrogen; R.sup.1-3-5, R.sup.1-3-6, R.sup.1-3-7, R.sup.1-3-8, R.sup.1-3-9 and R.sup.1-3-10 are independently hydrogen, C.sub.1-C.sub.7 alkyl or C.sub.3-C.sub.14 cycloalkyl; R.sup.1-3-11 is independently halogen, hydroxyl, amino, mercapto, cyano, C.sub.1-C.sub.7 alkyl, C.sub.1-C.sub.7 alkoxy, C.sub.1-C.sub.7 alkylthio, C.sub.3-C.sub.14 cycloalkyl, C.sub.3-C.sub.14 heterocycloalkyl, C.sub.6-C.sub.10 aryl, C.sub.1-C.sub.7 heteroaryl or “amino substituted by one or two R.sup.1-3-11”; R.sup.1-3-11-1 is independently C.sub.1-C.sub.7 alkyl or C.sub.3-C.sub.14 cycloalkyl; R.sup.1-5 is independently hydrogen, —NR.sup.1-5-1R.sup.1-5-2, —OR.sup.1-5-3 or “C.sub.1-C.sub.7 alkyl, C.sub.3-C.sub.14 cycloalkyl, C.sub.3-C.sub.14 heterocycloalkyl, C.sub.6-C.sub.10 aryl or C.sub.1-C.sub.7 heteroaryl” optionally substituted by one, two or three R.sup.1-5-4; R.sup.1-5-1 and R.sup.1-5-2 are independently hydrogen, C.sub.1-C.sub.7 alkyl or C.sub.3-C.sub.14 cycloalkyl; R.sup.1-5-3 is independently hydrogen, C.sub.1-C.sub.7 alkyl, C.sub.3-C.sub.14 cycloalkyl, C.sub.3-C.sub.14 heterocycloalkyl, C.sub.6-C.sub.10 aryl or C.sub.1-C.sub.7 heteroaryl; R.sup.1-5-4 is independently halogen, hydroxyl, amino, mercapto, cyano, C.sub.1-C.sub.7 alkyl, C.sub.1-C.sub.7 alkoxy, C.sub.1-C.sub.7 alkylthio, C.sub.3-C.sub.14 cycloalkyl, C.sub.3-C.sub.14 heterocycloalkyl, C.sub.6-C.sub.10 aryl, C.sub.1-C.sub.7 heteroaryl or “amino substituted by one or two R.sup.1-5-4-1”; R.sup.1-5-4-1 is independently C.sub.1-C.sub.7 alkyl or C.sub.3-C.sub.14 cycloalkyl; R.sup.1-6 is independently hydrogen, —CN, —OH; R.sup.1-7 is independently hydrogen, —NR.sup.1-7-2R.sup.1-7-3; R.sup.1-7-2 and R.sup.1-7-3 are independently C.sub.1-C.sub.7 alkyl or C.sub.3-C.sub.14 cycloalkyl; or, R.sup.1-7-2 and R.sup.1-7-3 together with the nitrogen atom they are attached to form a C.sub.3-C.sub.14 heterocycloalkyl optionally substituted by one, two or three R.sup.1-7-2-1; one or more methylenes in the C.sub.3-C.sub.14 heterocycloalkyl are optionally and independently substituted by oxygen atom, sulfur atom; R.sup.1-7-2-1 is independently C.sub.1-C.sub.7 alkyl or C.sub.3-C.sub.14 cycloalkyl; R.sup.1-8 is independently oxo, halogen, —OH, amino, mercapto, cyano, C.sub.1-C.sub.7 alkyl, C.sub.1-C.sub.7 alkoxy, C.sub.1-C.sub.7 alkylthio, C.sub.3-C.sub.14 cycloalkyl, C.sub.3-C.sub.14 heterocycloalkyl, C.sub.6-C.sub.10 aryl, C.sub.1-C.sub.7 heteroaryl or “amino substituted by one or two R.sup.1-8-1”; R.sup.1-8-1 is independently C.sub.1-C.sub.7 alkyl or C.sub.3-C.sub.14 cycloalkyl; R.sup.1-9 is independently hydrogen or C.sub.1-C.sub.7 alkyl; R.sup.2 is “C.sub.2-C.sub.7 alkyl, C.sub.3-C.sub.14 cycloalkyl or C.sub.3-C.sub.14 heterocycloalkyl” optionally substituted by one, two or three R.sup.2-2; R.sup.2-2 is independently halogen or hydroxyl; in any one of the above cases, the heteroatoms in the C.sub.3-C.sub.14 heterocycloalkyl, C.sub.1-C.sub.7 heteroaryl are independently selected from one or more of boron, silicon, oxygen, sulfur, selenium, nitrogen and phosphorus; the number of heteroatoms is independently 1, 2, 3 or 4; scheme (8): A is C.sub.3-C.sub.20 cycloalkyl substituted by one or two R.sup.1; X is CH or N; R.sup.1 is independently cyano, halogen, —NR.sup.1-3R.sup.1-4, —C(═O)R.sup.1-5, —C(═NR.sup.1-6)R.sup.1-7, ═N—O—R.sup.1-9, C.sub.1-C.sub.7 heteroaryl or “C.sub.3-C.sub.14 heterocycloalkyl” optionally substituted by one R.sup.1-8; R.sup.1-3 and R.sup.1-4 are independently hydrogen, —S(═O).sub.2R.sup.1-3-1, —C(═O)R.sup.1-3-2, —C(═NR.sup.1-3-3)NR.sup.1-3-5R.sup.1-3-6, or C.sub.1-C.sub.7 alkyl; R.sup.1-3-1 and R.sup.1-3-2 are independently C.sub.1-C.sub.7 alkyl, or C.sub.3-C.sub.14 cycloalkyl; R.sup.1-3-3 is hydrogen; R.sup.1-3-5 and R.sup.1-3-6 are hydrogen; R.sup.1-5 is independently —NR.sup.1-5-1R.sup.1-5-2, —OR.sup.1-5-3 or C.sub.3-C.sub.14 heterocycloalkyl; R.sup.1-5-1 and R.sup.1-5-2 are independently hydrogen, C.sub.1-C.sub.7 alkyl or C.sub.3-C.sub.14 cycloalkyl; R.sup.1-5-3 is independently hydrogen or C.sub.1-C.sub.7 alkyl; R.sup.1-8 is independently oxo; R.sup.1-9 is independently hydrogen or C.sub.1-C.sub.7 alkyl; R.sup.2 is “C.sub.2-C.sub.7 alkyl or C.sub.3-C.sub.14 heterocycloalkyl substituted by one R.sup.2-2”; R.sup.2-2 is halogen or hydroxyl; scheme (9): A is C.sub.3-C.sub.20 cycloalkyl substituted by one R.sup.1; X is CH or N; R.sup.1 is —CN, —NR.sup.1-3R.sup.1-4, —C(═O)R.sup.1-5, ═N—O—R.sup.1-9 or “C.sub.3-C.sub.14 heterocycloalkyl” optionally substituted by one R.sup.1-8; R.sup.1-3 and R.sup.1-4 are independently hydrogen, —S(═O).sub.2R.sup.1-3-1, —C(═O)R.sup.1-3-2, —C(═NR.sup.1-3-3)NR.sup.1-3-5R.sup.1-3-6 or C.sub.1-C.sub.7 alkyl; R.sup.1-3-1 and R.sup.1-3-2 are independently C.sub.1-C.sub.7 alkyl, or C.sub.3-C.sub.14 cycloalkyl; R.sup.1-3-3 is hydrogen; R.sup.1-3-5 and R.sup.1-3-6 are hydrogen; R.sup.1-5 is —NR.sup.1-5-1R.sup.1-5-2, —OR.sup.1-5-3 or C.sub.3-C.sub.14 heterocycloalkyl; R.sup.1-5-1 and R.sup.1-5-2 are independently hydrogen, C.sub.1-C.sub.7 alkyl or C.sub.3-C.sub.14 cycloalkyl; R.sup.1-5-3 is independently hydrogen or C.sub.1-C.sub.7 alkyl; R.sup.1-8 is independently oxo; R.sup.1-9 is independently hydrogen or C.sub.1-C.sub.7 alkyl; R.sup.2 is “C.sub.2-C.sub.7 alkyl or C.sub.3-C.sub.14 heterocycloalkyl substituted by one R.sup.2-2”; R.sup.2-2 is hydroxyl; scheme (10): A is C.sub.3-C.sub.20 cycloalkyl substituted by one R.sup.1; X is CH or N; R.sup.1 is —CN, —NR.sup.1-3R.sup.1-4, —C(═O)R.sup.1-5, ═N—O—R.sup.1-9, or “C.sub.3-C.sub.14 heterocycloalkyl” optionally substituted by one R.sup.1-8; R.sup.1-3 and R.sup.1-4 are independently hydrogen, —S(═O).sub.2R.sup.1-3-1, —C(═O)R.sup.1-3-2, —C(═NR.sup.1-3-3)NR.sup.1-3-5R.sup.1-3-6, or C.sub.1-C.sub.7 alkyl; R.sup.1-3-1 and R.sup.1-3-2 are independently C.sub.1-C.sub.7 alkyl, or C.sub.3-C.sub.14 cycloalkyl; R.sup.1-3-3 is hydrogen; R.sup.1-3-5 and R.sup.1-3-6 are hydrogen; R.sup.1-5 is —NR.sup.1-5-1R.sup.1-5-2, —OR.sup.1-5-3 or C.sub.3-C.sub.14 heterocycloalkyl; R.sup.1-5-1 and R.sup.1-5-2 are independently hydrogen, C.sub.1-C.sub.7 alkyl or C.sub.3-C.sub.14 cycloalkyl; R.sup.1-5-3 is hydrogen; R.sup.1-8 is independently oxo; R.sup.1-9 is independently hydrogen or C.sub.1-C.sub.7 alkyl; R.sup.2 is “C.sub.2-C.sub.7 alkyl or C.sub.3-C.sub.14 heterocycloalkyl substituted by one R.sup.2-2”; R.sup.2-2 is hydroxyl; scheme (11): A is R or R ##STR00222## X is CH or N; R.sup.1 is —CN, —NR.sup.1-3R.sup.1-4, —C(═O)R.sup.1-5, ═N—O—R.sup.1-9, or “C.sub.3-C.sub.14 heterocycloalkyl” optionally substituted by one R.sup.1-8; R.sup.1-3 and R.sup.1-4 are independently hydrogen, —S(═O).sub.2R.sup.1-3-1, —C(═O)R.sup.1-3-2, —C(═NR.sup.1-3-3)NR.sup.1-3-5R.sup.1-3-6 or C.sub.1-C.sub.7 alkyl; R.sup.1-3-1 and R.sup.1-3-2 are independently C.sub.1-C.sub.7 alkyl, or C.sub.3-C.sub.14 cycloalkyl; R.sup.1-3-3 is hydrogen; R.sup.1-3-5 and R.sup.1-3-6 are hydrogen; R.sup.1-5 is —NR.sup.1-5-1R.sup.1-5-2, —OR.sup.1-5-3 or C.sub.3-C.sub.14 heterocycloalkyl; R.sup.1-5-1 and R.sup.1-5-2 are independently hydrogen, C.sub.1-C.sub.7 alkyl or C.sub.3-C.sub.14 cycloalkyl; R.sup.1-5-3 is hydrogen or C.sub.1-C.sub.7 alkyl; R.sup.1-8 is independently oxo; R.sup.1-9 is independently hydrogen or C.sub.1-C.sub.7 alkyl; R.sup.2 is “C.sub.2-C.sub.7 alkyl or C.sub.3-C.sub.14 heterocycloalkyl substituted by one R.sup.2-2”; R.sup.2-2 is hydroxyl; scheme (12): A is ##STR00223## X is CH or N; R.sup.1 is independently —CN, —NR.sup.1-3R.sup.1-4, —C(═O)R.sup.1-5, ═N—O—R.sup.1-9, or “C.sub.3-C.sub.14 heterocycloalkyl” optionally substituted by one R.sup.1-8; R.sup.1-3 and R.sup.1-4 are independently hydrogen, —S(═O).sub.2R.sup.1-3-1, —C(═O)R.sup.1-3-2, —C(═NR.sup.1-3-3)NR.sup.1-3-5R.sup.1-3-6 or C.sub.1-C.sub.7 alkyl; R.sup.1-3-1 and R.sup.1-3-2 are independently C.sub.1-C.sub.7 alkyl, or C.sub.3-C.sub.14 cycloalkyl; R.sup.1-3-3 is hydrogen; R.sup.1-3-5 and R.sup.1-3-6 are hydrogen; R.sup.1-5 is independently —NR.sup.1-5-1R.sup.1-5-2, —OR.sup.1-5-3, or C.sub.3-C.sub.14 heterocycloalkyl; R.sup.1-5-1 and R.sup.1-5-2 are independently hydrogen, C.sub.1-C.sub.7 alkyl, or C.sub.3-C.sub.14 cycloalkyl; R.sup.1-5-3 is independently hydrogen or C.sub.1-C.sub.7 alkyl; R.sup.1-8 is independently oxo; R.sup.1-9 is independently hydrogen or C.sub.1-C.sub.7 alkyl; R.sup.2 is ##STR00224##

12. The pyrazolone-fused pyrimidine compound represented by formula II according to claim 1, the pharmaceutically acceptable salt thereof, the solvate thereof, the solvate of the pharmaceutically acceptable salt thereof, the metabolite thereof or the prodrug thereof, wherein, the pyrazolone-fused pyrimidine compound represented by formula II is any of the compounds described in any of the following schemes: scheme A: ##STR00225## ##STR00226## ##STR00227## ##STR00228## ##STR00229## ##STR00230## ##STR00231## ##STR00232## ##STR00233## ##STR00234## ##STR00235## ##STR00236## ##STR00237## ##STR00238## scheme B: ##STR00239## its .sup.1H NMR (400 MHz, MeOD) is δ 8.85 (s, 1H), 8.00 (t, J=7.9 Hz, 1H), 7.80 (d, J=8.1 Hz, 1H), 7.68 (d, J=7.7 Hz, 1H), 7.62 (d, J=8.6 Hz, 2H), 7.28 (d, J=8.6 Hz, 2H), 5.78-5.68 (m, 1H), 5.06 (d, J=10.3 Hz, 1H), 4.95 (s, 1H), 4.82 (s, 2H), 3.82-3.76 (m, 1H), 2.81 (s, 1H), 2.71 (s, 3H), 2.49 (s, 1H), 2.08 (d, J=10.9 Hz, 3H), 1.94 (d, J=15.0 Hz, 3H), 1.72 (s, 4H), 1.59 (d, J=7.0 Hz, 6H); ##STR00240## its .sup.1H NMR (400 MHz, CDCl.sub.3) is δ 8.87 (d, J=2.1 Hz, 1H), 7.91 (td, J=7.9, 1.5 Hz, 1H), 7.78 (d, J=8.0 Hz, 1H), 7.54 (t, J=7.9 Hz, 2H), 7.39 (d, J=7.7 Hz, 1H), 7.21 (d, J=8.5 Hz, 2H), 5.72 (ddt, J=16.4, 10.2, 6.2 Hz, 1H), 5.07 (dd, J=10.2, 1.1 Hz, 1H), 4.96 (dd, J=17.1, 1.2 Hz, 1H), 4.77 (d, J=6.2 Hz, 2H), 4.25-4.10 (m, 2H), 3.95 (s, 1H), 2.73 (s, 1H), 2.56 (dt, J=15.5, 10.8 Hz, 1H), 2.28 (d, J=7.9 Hz, 1H), 2.14 (d, J=10.6 Hz, 1H), 2.05-1.97 (m, 1H), 1.78 (dd, J=19.0, 8.5 Hz, 1H), 1.67 (dt, J=10.1, 6.1 Hz, 3H), 1.61 (s, 6H), 1.59-1.44 (m, 1H), 1.34-1.26 (m, 3H); ##STR00241## its .sup.1H NMR (400 MHz, MeOD) is δ 8.84 (d, J=1.4 Hz, 1H), 8.00 (td, J=7.9, 4.0 Hz, 1H), 7.83-7.76 (m, 1H), 7.67 (dd, J=7.7, 0.7 Hz, 1H), 7.60 (dd, J=8.4, 5.7 Hz, 2H), 7.19 (dd, J=13.2, 8.6 Hz, 2H), 5.73 (ddd, J=17.0, 6.1, 4.1 Hz, 1H), 5.08-5.03 (m, 1H), 4.95 (d, J=1.3 Hz, 1H), 4.86-4.79 (m, 2H), 2.72 (s, 1H), 2.58 (s, 1H), 2.27 (d, J=6.7 Hz, 1H), 2.13 (d, J=10.0 Hz, 1H), 1.96 (d, J=10.2 Hz, 1H), 1.80-1.66 (m, 4H), 1.64-1.52 (m, 7H); ##STR00242## its .sup.1H NMR (400 MHz, CDCl.sub.3) is δ 8.86 (d, J=4.2 Hz, 1H), 7.97-7.88 (m, 1H), 7.79 (d, J=8.0 Hz, 1H), 7.53 (dd, J=12.3, 8.5 Hz, 2H), 7.39 (d, J=7.6 Hz, 1H), 7.28-7.15 (m, 2H), 5.80-5.65 (m, 1H), 5.06 (d, J=10.0 Hz, 1H), 4.95 (d, J=17.1 Hz, 1H), 4.77 (d, J=6.0 Hz, 2H), 3.10 (d, J=12.1 Hz, 3H), 2.98 (s, 3H), 2.67-2.57 (m, 1H), 2.14 (dd, J=20.9, 10.3 Hz, 1H), 2.06-1.97 (m, 2H), 1.92 (d, J=14.0 Hz, 1H), 1.78-1.66 (m, 4H), 1.61 (s, 6H), 1.49 (dd, J=22.8, 12.2 Hz, 1H); ##STR00243## its .sup.1H NMR (400 MHz, CDCl.sub.3) is δ 8.85 (d, J=4.7 Hz, 1H), 7.91 (dt, J=10.7, 7.9 Hz, 1H), 7.78 (d, J=7.8 Hz, 1H), 7.53 (dd, J=12.0, 8.5 Hz, 2H), 7.39 (dd, J=7.6, 2.4 Hz, 1H), 7.22 (dd, J=19.5, 8.5 Hz, 2H), 5.71 (ddt, J=16.4, 10.2, 6.2 Hz, 1H), 5.06 (d, J=10.2 Hz, 1H), 4.95 (d, J=17.1 Hz, 1H), 4.77 (d, J=6.1 Hz, 2H), 4.21 (dd, J=16.4, 8.6 Hz, 2H), 4.10-4.02 (m, 2H), 2.63-2.52 (m, 2H), 2.35-2.20 (m, 2H), 2.15-2.07 (m, 1H), 2.00 (dd, J=13.4, 3.0 Hz, 2H), 1.92-1.83 (m, 1H), 1.79-1.63 (m, 4H), 1.60 (s, 6H), 1.48 (ddd, J=24.7, 12.5, 2.5 Hz, 1H); ##STR00244## its .sup.1H NMR (400 MHz, CDCl.sub.3) is δ 8.86 (s, 1H), 7.93-7.85 (m, 1H), 7.78 (d, J=7.8 Hz, 1H), 7.52 (d, J=8.5 Hz, 2H), 7.39 (dd, J=7.6, 0.7 Hz, 1H), 7.19 (d, J=8.5 Hz, 2H), 5.71 (ddt, J=16.4, 10.2, 6.2 Hz, 1H), 5.05 (dd, J=10.2, 1.1 Hz, 1H), 4.94 (dd, J=17.1, 1.3 Hz, 1H), 4.77 (d, J=6.2 Hz, 2H), 4.11 (d, J=8.9 Hz, 1H), 3.24 (t, J=7.0 Hz, 4H), 2.52-2.43 (m, 1H), 2.14-2.00 (m, 3H), 1.92 (d, J=11.2 Hz, 4H), 1.60 (s, 6H), 1.45 (dt, J=14.9, 7.5 Hz, 2H), 1.23-1.08 (m, 2H); ##STR00245## its .sup.1H NMR (400 MHz, CDCl.sub.3) is δ 8.84 (d, J=3.7 Hz, 1H), 7.94 (dd, J=14.8, 6.9 Hz, 1H), 7.76 (d, J=7.9 Hz, 1H), 7.58-7.50 (m, 2H), 7.42 (dd, J=7.5, 4.1 Hz, 1H), 7.22 (dd, J=15.8, 8.5 Hz, 2H), 5.71 (dd, J=11.5, 5.4 Hz, 2H), 5.07 (d, J=10.2 Hz, 1H), 4.95 (d, J=17.1 Hz, 1H), 4.77 (d, J=6.1 Hz, 2H), 2.82-2.72 (m, 1H), 2.60 (s, 1H), 2.12-2.01 (m, 3H), 1.92 (d, J=12.5 Hz, 1H), 1.81-1.67 (m, 3H), 1.62 (s, 6H), 1.54-1.43 (m, 1H), 0.93-0.78 (m, 3H), 0.52 (s, 2H); ##STR00246## its .sup.1H NMR (400 MHz, CDCl.sub.3) is δ 8.88 (s, 1H), 7.91 (t, J=7.9 Hz, 1H), 7.77 (d, J=7.9 Hz, 1H), 7.56 (d, J=8.5 Hz, 2H), 7.40 (d, J=7.4 Hz, 1H), 7.19 (d, J=8.5 Hz, 2H), 5.78-5.66 (m, 1H), 5.07 (dd, J=10.2, 1.0 Hz, 1H), 4.96 (dd, J=17.1, 1.2 Hz, 1H), 4.77 (d, J=6.2 Hz, 2H), 4.42 (d, J=7.6 Hz, 1H), 3.49-3.35 (m, 1H), 3.04 (s, 3H), 2.57-2.46 (m, 1H), 2.29-2.17 (m, 2H), 2.05-1.96 (m, 8H), 1.56-1.65 (m, 2H), 1.41-1.50 (m, 2H); ##STR00247## its .sup.1H NMR (400 MHz, MeOD) is δ 8.84 (s, 1H), 8.02 (m, 1H), 7.80 (m, 1H), 7.72-7.58 (m, 3H), 7.25 (m, 2H), 5.73 (ddt, J=16.5, 10.3, 6.1 Hz, 1H), 5.05 (dd, J=10.2, 1.0 Hz, 1H), 4.95 (d, 1H), 4.83 (d, J=6.1 Hz, 2H), 3.54-3.42 (m, 1H), 2.59 (m, 1H), 2.14 (m, 1H), 1.98 (m, 2H), 1.83 (m, 1H), 1.68 (m, 2H), 1.60 (s, 6H), 1.50 (m, 2H); ##STR00248## its .sup.1H NMR (400 MHz, DMSO) is δ 10.28 (s, 1H), 8.88 (d, J=1.8 Hz, 1H), 8.09-7.97 (m, 1H), 7.75 (d, J=8.4 Hz, 1H), 7.66 (dd, J=20.6, 8.5 Hz, 3H), 7.19 (dd, J=11.1, 8.7 Hz, 2H), 5.74-5.61 (m, 1H), 5.00 (d, J=10.2 Hz, 1H), 4.82 (d, J=17.1 Hz, 1H), 4.69 (d, J=5.5 Hz, 2H), 3.23 (s, 1H), 2.74 (t, J=12.1 Hz, 1H), 2.53 (s, 1H), 2.12 (d, J=10.1 Hz, 1H), 1.98 (d, J=13.2 Hz, 1H), 1.82 (d, J=13.2 Hz, 2H), 1.77-1.57 (m, 3H), 1.49 (d, J=18.2 Hz, 6H); ##STR00249## its .sup.1H NMR (400 MHz, DMSO) is δ 10.27 (s, 1H), 8.89 (s, 1H), 8.12 (s, 1H), 7.74 (dd, J=22.6, 8.3 Hz, 3H), 7.64 (d, J=7.3 Hz, 1H), 7.37 (d, J=8.5 Hz, 2H), 5.76-5.61 (m, 1H), 5.34 (s, 1H), 5.01 (dd, J=10.3, 1.2 Hz, 1H), 4.84 (d, J=17.1 Hz, 1H), 4.70 (d, J=5.7 Hz, 2H), 3.62 (s, 1H), 3.12 (s, 1H), 2.71-2.58 (m, 8H), 2.38 (d, J=9.2 Hz, 2H), 1.47 (s, 6H), 1.32-1.24 (m, 1H); ##STR00250## its .sup.1H NMR (400 MHz, DMSO) is δ 10.26 (s, 1H), 8.88 (s, 1H), 8.07 (t, J=7.8 Hz, 1H), 7.76 (d, J=8.0 Hz, 1H), 7.65 (dd, J=14.5, 7.9 Hz, 2H), 7.22 (d, J=8.5 Hz, 2H), 5.74-5.60 (m, 1H), 5.35 (s, 1H), 5.00 (d, J=10.3 Hz, 1H), 4.83 (d, J=17.1 Hz, 1H), 4.69 (d, J=5.6 Hz, 2H), 3.74 (s, 3H), 3.24-3.15 (m, 1H), 2.77 (t, J=12.0 Hz, 1H), 2.37 (d, J=14.0 Hz, 1H), 2.25 (td, J=13.4, 4.6 Hz, 1H), 1.99-1.84 (m, 3H), 1.67-1.50 (m, 2H), 1.49 (d, J=14.0 Hz, 6H); ##STR00251## its .sup.1H NMR (400 MHz, MeOD) is δ 8.86 (s, 0H), 8.11-8.01 (m, 1H), 7.94 (d, J=7.9 Hz, 2H), 7.67 (d, J=7.6 Hz, 2H), 7.62 (d, J=8.6 Hz, 2H), 7.28 (d, J=8.5 Hz, 2H), 5.83-5.74 (m, 1H), 5.09 (dd, J=7.9, 4.4 Hz, 3H), 4.98 (dd, J=17.1, 1.3 Hz, 2H), 4.85 (d, J=6.7 Hz, 2H), 2.87 (s, 1H), 2.64 (s, 1H), 2.47 (s, 3H), 1.97-1.67 (m, 8H); ##STR00252## its .sup.1H NMR (400 MHz, MeOD) is δ 8.87 (d, J=6.6 Hz, 1H), 8.06 (t, J=7.9 Hz, 1H), 7.95 (d, J=7.9 Hz, 1H), 7.68 (dd, J=7.8, 5.4 Hz, 2H), 7.61 (d, J=8.6 Hz, 1H), 7.41 (d, J=8.4 Hz, 1H), 7.24 (t, J=8.7 Hz, 1H), 5.84-5.72 (m, 1H), 5.09 (d, J=6.2 Hz, 2H), 5.07 (d, J=1.3 Hz, 1H), 5.02-4.94 (m, 2H), 4.90 (s, 2H), 4.84 (d, J=6.7 Hz, 2H), 3.15 (d, J=2.6 Hz, 1H), 3.08 (s, 1H), 2.95 (s, 1H), 2.71 (s, 1H), 2.43 (s, 1H), 1.93-2.03 (m, 3H), 1.76 (s, 2H), 1.51 (s, 1H), 1.31 (d, J=4.3 Hz, 3H), 0.89 (dd, J=20.1, 9.0 Hz, 4H); ##STR00253## its .sup.1H NMR (400 MHz, CDCl.sub.3) is δ 8.87-8.79 (m, 1H), 8.14-8.07 (m, 1H), 8.04-7.96 (m, 1H), 7.89-7.80 (m, 1H), 7.61-7.50 (m, 2H), 7.38-7.32 (m, 1H), 7.25-7.19 (m, 1H), 7.01 (t, J=3.4 Hz, 1H), 5.72 (ddd, J=16.6, 11.1, 8.6 Hz, 1H), 5.17-5.09 (m, 2H), 5.04-4.98 (m, 1H), 4.98-4.92 (m, 1H), 4.87-4.77 (m, 2H), 4.73-4.64 (m, 2H), 4.20-4.06 (m, 1H), 3.47-3.38 (m, 1H), 3.38-3.29 (m, 1H), 3.05-2.98 (m, 1H), 2.49-2.35 (m, 2H), 2.27-2.17 (m, 1H), 2.07-1.86 (m, 4H), 1.75-1.60 (m, 3H); ##STR00254## its .sup.1H NMR (400 MHz, CDCl.sub.3) is δ 8.77 (s, 1H), 8.16-8.07 (m, 1H), 8.03 (d, J=7.6 Hz, 1H), 7.83-7.75 (m, 1H), 7.56 (dd, J=12.6, 6.1 Hz, 2H), 7.33 (d, J=8.5 Hz, 1H), 7.21 (d, J=8.5 Hz, 1H), 5.72 (dd, J=17.0, 10.3 Hz, 1H), 5.13 (dd, J=9.1, 6.1 Hz, 2H), 4.96 (d, J=17.0 Hz, 2H), 4.81 (d, J=7.2 Hz, 2H), 4.69 (d, J=6.2 Hz, 2H), 4.41-4.28 (m, 2H), 3.86 (s, 1H), 3.77 (t, J=6.6 Hz, 1H), 3.63-3.50 (m, 2H), 2.98 (m, 1H), 2.15 (m, 1H), 1.97 (dd, J=18.9, 9.6 Hz, 2H), 1.78 (d, J=5.0 Hz, 2H), 1.65 (d, J=8.7 Hz, 2H); ##STR00255## its .sup.1H NMR (400 MHz, CDCl.sub.3) is δ 8.69 (s, 1H), 8.18 (d, J=8.0 Hz, 1H), 8.10 (dd, J=17.9, 7.6 Hz, 1H), 7.81-7.72 (m, 1H), 7.63-7.49 (m, 2H), 7.25 (d, J=8.4 Hz, 1H), 7.19 (d, J=8.3 Hz, 1H), 5.70 (d, J=6.8 Hz, 1H), 5.15 (d, J=10.1 Hz, 1H), 5.14-5.07 (m, 1H), 4.95 (d, J=16.6 Hz, 1H), 4.83 (t, J=6.7 Hz, 2H), 4.71 (s, 2H), 2.54 (dd, J=24.9, 12.6 Hz, 2H), 2.30 (d, J=11.2 Hz, 1H), 2.18 (d, J=13.5 Hz, 1H), 2.02 (d, J=12.9 Hz, 1H), 1.96-1.80 (m, 2H), 1.78 (d, J=16.1 Hz, 1H), 1.49 (dd, J=26.4, 11.2 Hz, 2H); ##STR00256## its .sup.1H NMR (400 MHz, Methanol-d.sub.4) is δ 8.85 (d, J=1.1 Hz, 1H), 8.05 (td, J=7.9, 4.8 Hz, 1H), 7.96-7.86 (m, 1H), 7.67 (d, J=7.6 Hz, 1H), 7.59 (ddd, J=9.2, 4.6, 2.3 Hz, 2H), 7.25-7.19 (m, 1H), 7.19-7.11 (m, 1H), 5.78 (ddt, J=16.5, 10.1, 6.1 Hz, 1H), 5.12-5.07 (m, 2H), 5.06 (t, J=1.3 Hz, 1H), 4.98 (dd, J=17.0, 1.4 Hz, 1H), 4.90 (d, J=1.4 Hz, 2H), 4.25-4.19 (m, 1H), 4.14 (dd, J=14.1, 7.1 Hz, 1H), 2.34-2.12 (m, 2H), 2.07 (dd, J=17.0, 4.1 Hz, 1H), 1.99-1.82 (m, 1H), 1.74-1.65 (m, 2H), 1.65-1.53 (m, 2H), 1.31 (d, J=4.2 Hz, 3H), 1.29-1.25 (m, 2H); ##STR00257## its .sup.1H NMR (400 MHz, Methanol-d.sub.4) is δ 8.84 (s, 1H), 8.05 (t, J=7.9 Hz, 1H), 7.92 (d, J=8.1 Hz, 1H), 7.66 (dd, J=7.6, 0.9 Hz, 1H), 7.63-7.53 (m, 2H), 7.22-7.14 (m, 2H), 5.84-5.74 (m, 1H), 5.10-5.07 (m, 2H), 5.06 (q, J=1.3 Hz, 1H), 4.98 (dq, J=17.0, 1.4 Hz, 1H), 4.89 (dt, J=6.1, 1.4 Hz, 2H), 2.71 (d, J=6.9 Hz, 1H), 2.59 (s, 1H), 2.24 (dd, J=16.4, 7.8 Hz, 2H), 2.04 (d, J=8.5 Hz, 1H), 1.73 (td, J=10.9, 6.8 Hz, 6H); scheme C: ##STR00258## ##STR00259## ##STR00260## ##STR00261## ##STR00262## ##STR00263## ##STR00264## ##STR00265## ##STR00266## ##STR00267## ##STR00268## ##STR00269## ##STR00270## ##STR00271## scheme D: ##STR00272## (I-1-1), its .sup.1H NMR (400 MHz, MeOD) is δ 8.85 (s, 1H), 8.46 (s, 2H), 7.99 (t, J=7.9 Hz, 1H), 7.79 (d, J=8.0 Hz, 1H), 7.65 (dd, J=16.6, 8.1 Hz, 3H), 7.22 (d, J=8.6 Hz, 2H), 5.73 (ddt, J=16.3, 10.2, 6.1 Hz, 1H), 5.05 (dd, J=10.3, 1.1 Hz, 1H), 4.93 (dd, J=17.1, 1.3 Hz, 1H), 4.82 (d, J=6.1 Hz, 2H), 2.90 (s, 6H), 2.60 (d, J=8.4 Hz, 1H), 2.21 (s, 2H), 2.10 (d, J=10.6 Hz, 2H), 1.70 (d, J=11.4 Hz, 4H), 1.59 (s, 6H); ##STR00273## (I-1-2), its .sup.1H NMR (400 MHz, CDCl.sub.3) is δ 8.86 (s, 1H), 8.54 (s, 1H), 7.95 (t, J=7.9 Hz, 1H), 7.75 (d, J=8.0 Hz, 1H), 7.59 (d, J=8.5 Hz, 2H), 7.43 (d, J=7.6 Hz, 1H), 7.32 (d, J=8.5 Hz, 2H), 5.72 (ddt, J=16.5, 10.3, 6.2 Hz, 1H), 5.06 (d, J=10.2 Hz, 1H), 4.95 (dd, J=17.1, 1.0 Hz, 1H), 4.75 (d, J=6.1 Hz, 2H), 3.05 (m, 1H), 2.93 (m, 1H), 2.68 (s, 6H), 2.32 (m, 2H), 1.84 (m, 6H), 1.60 (s, 6H); ##STR00274## (I-3-1), its .sup.1H NMR (400 MHz, CDCl.sub.3) is δ 8.87 (s, 1H), 7.90 (t, J=7.9 Hz, 1H), 7.78 (d, J=8.0 Hz, 1H), 7.53 (d, J=8.5 Hz, 2H), 7.39 (dd, J=7.6, 0.5 Hz, 1H), 7.20 (d, J=8.5 Hz, 2H), 5.72 (ddt, J=16.4, 10.2, 6.2 Hz, 1H), 5.06 (dd, J=10.2, 1.0 Hz, 1H), 4.95 (dd, J=17.1, 1.2 Hz, 1H), 4.76 (d, J=6.2 Hz, 2H), 4.04 (s, 1H), 2.66 (m, 4H), 2.58-2.47 (m, 1H), 2.16 (m, 4H), 1.96 (m, 2H), 1.87-1.78 (m, 4H), 1.60 (s, 6H), 1.58-1.39 (m, 4H); ##STR00275## (I-3-2), its .sup.1H NMR (400 MHz, CDCl.sub.3) is δ 8.87 (s, 1H), 7.92 (t, J=7.9 Hz, 1H), 7.80 (d, J=8.0 Hz, 1H), 7.52 (d, J=8.5 Hz, 2H), 7.38 (d, J=7.6 Hz, 1H), 7.29 (t, J=4.2 Hz, 2H), 5.79-5.66 (m, 1H), 5.06 (dd, J=10.2, 1.0 Hz, 1H), 4.96 (dd, J=17.1, 1.2 Hz, 1H), 4.77 (d, J=6.2 Hz, 2H), 4.02 (s, 1H), 2.70-2.50 (m, 5H), 2.26 (s, 1H), 1.98 (m, 4H), 1.82 (s, 4H), 1.69-1.56 (m, 10H); ##STR00276## (I-8-1), its .sup.1H NMR (400 MHz, CDCl.sub.3) is δ 8.86 (s, 1H), 7.93-7.85 (m, 1H), 7.78 (d, J=7.8 Hz, 1H), 7.52 (d, J=8.5 Hz, 2H), 7.39 (dd, J=7.6, 0.7 Hz, 1H), 7.19 (d, J=8.5 Hz, 2H), 5.71 (ddt, J=16.4, 10.2, 6.2 Hz, 1H), 5.05 (dd, J=10.2, 1.1 Hz, 1H), 4.94 (dd, J=17.1, 1.3 Hz, 1H), 4.77 (d, J=6.2 Hz, 2H), 4.11 (d, J=8.9 Hz, 1H), 3.24 (t, J=7.0 Hz, 4H), 2.52-2.43 (m, 1H), 2.14-2.00 (m, 3H), 1.92 (d, J=11.2 Hz, 4H), 1.60 (s, 6H), 1.45 (dt, J=14.9, 7.5 Hz, 2H), 1.23-1.08 (m, 2H); ##STR00277## (I-8-2), its .sup.1H NMR (400 MHz, CDCl.sub.3) is δ8.87 (s, 1H), 7.92 (d, J=7.8 Hz, 1H), 7.80 (d, J=8.0 Hz, 1H), 7.52 (d, J=8.4 Hz, 2H), 7.39 (d, J=7.6 Hz, 1H), 7.29-7.25 (m, 2H), 5.82-5.63 (m, 1H), 5.12-4.91 (m, 2H), 4.78 (d, J=6.2 Hz, 2H), 4.01 (s, 1H), 3.17 (s, 4H), 2.53 (s, 1H), 2.33 (s, 1H), 2.06 (d, J=4.4 Hz, 2H), 1.89 (d, J=11.6 Hz, 2H), 1.75 (d, J=14.1 Hz, 2H), 1.59 (d, J=17.2 Hz, 8H), 1.46 (t, J=13.1 Hz, 2H); ##STR00278## (I-15-1), its .sup.1H NMR (400 MHz, MeOD) is δ 8.84 (s, 1H), 8.04 (t, J=7.9 Hz, 1H), 7.92 (d, J=8.1 Hz, 1H), 7.67 (d, J=7.6 Hz, 1H), 7.60 (d, J=8.6 Hz, 2H), 7.21 (d, J=8.6 Hz, 2H), 5.78 (ddt, J=16.3, 10.3, 6.1 Hz, 1H), 5.12-5.05 (m, 3H), 4.98 (dd, J=17.1, 1.3 Hz, 1H), 4.89 (d, J=6.1 Hz, 2H), 4.84 (s, 2H), 3.68 (s, 2H), 2.97-2.86 (m, 1H), 2.66 (s, 6H), 2.60-2.50 (m, 1H), 2.15 (d, J=8.6 Hz, 2H), 2.04 (d, J=9.0 Hz, 2H), 1.66-1.54 (m, 4H); ##STR00279## (I-15-2), its .sup.1H NMR (400 MHz, MeOD) is δ 8.83 (s, 1H), 8.04 (t, J=7.9 Hz, 1H), 7.92 (d, J=8.0 Hz, 1H), 7.67-7.62 (m, 1H), 7.59 (d, J=8.6 Hz, 2H), 7.29 (d, J=8.5 Hz, 2H), 5.76 (ddt, J=16.3, 10.2, 6.1 Hz, 1H), 5.10-5.02 (m, 3H), 4.96 (dd, J=17.1, 1.3 Hz, 1H), 4.87 (d, J=6.8 Hz, 2H), 4.82 (d, J=6.8 Hz, 2H), 2.73 (d, J=4.2 Hz, 1H), 2.29 (d, J=21.9 Hz, 7H), 2.04-1.90 (m, 4H), 1.66 (dd, J=15.6, 6.1 Hz, 4H); ##STR00280## (I-36-1), its .sup.1H NMR (400 MHz, CDCl.sub.3) is δ 8.88 (d, J=2.6 Hz, 1H), 8.09 (dd, J=15.0, 7.8 Hz, 1H), 7.99-7.83 (m, 2H), 7.54 (t, J=9.5 Hz, 2H), 7.39 (d, J=8.7 Hz, 1H), 7.21 (d, J=8.5 Hz, 1H), 5.74 (dq, J=10.5, 5.9 Hz, 1H), 5.12 (t, J=8.8 Hz, 3H), 4.99 (d, J=17.1 Hz, 1H), 4.80 (d, J=6.3 Hz, 2H), 4.67 (d, J=6.0 Hz, 2H), 3.39-3.24 (m, 4H), 2.60-2.34 (m, 3H), 2.14 (dt, J=14.0, 6.8 Hz, 3H), 1.96 (d, J=10.8 Hz, 4H), 1.55-1.37 (m, 2H), 1.27-1.12 (m, 2H); ##STR00281## (I-36-2), its .sup.1H NMR (400 MHz, MeOD) is δ 8.86 (s, 1H), 8.02 (dt, J=24.0, 7.9 Hz, 3H), 7.64 (dd, J=27.1, 8.1 Hz, 3H), 7.27 (t, J=8.6 Hz, 2H), 7.01-6.91 (m, 3H), 6.72-6.64 (m, 3H), 5.79 (ddd, J=16.3, 11.2, 6.1 Hz, 1H), 5.10-5.05 (m, 2H), 4.85 (d, J=6.8 Hz, 2H), 2.57 (d, J=10.7 Hz, 1H), 2.48-2.28 (m, 3H), 2.23-2.06 (m, 3H), 1.98-1.71 (m, 6H), 1.58 (dd, J=23.2, 12.9 Hz, 3H), 1.44 (ddd, J=16.1, 13.2, 3.5 Hz, 2H), 1.19-1.00 (m, 2H); ##STR00282## (I-41-1), its .sup.1H NMR (400 MHz, Chloroform-d) is δ 9.00 (s, 1H), 8.30 (d, J=8.6 Hz, 1H), 8.22 (d, J=2.4 Hz, 1H), 7.96 (t, J=7.9 Hz, 1H), 7.73 (dd, J=8.1, 0.8 Hz, 1H), 7.55 (dd, J=8.7, 2.4 Hz, 1H), 7.44 (dd, J=7.7, 0.8 Hz, 1H), 5.77-5.66 (m, 1H), 5.12-5.05 (m, 1H), 4.97 (dq, J=17.0, 1.4 Hz, 1H), 4.76 (dt, J=6.3, 1.3 Hz, 2H), 2.70 (s, 1H), 2.56 (s, 6H), 2.23 (q, J=9.5 Hz, 4H), 2.11-2.01 (m, 4H), 1.58 (t, J=10.3 Hz, 6H); ##STR00283## (I-41-2), its .sup.1H NMR (400 MHz, Chloroform-d) is δ8.99 (s, 1H), 8.54 (s, 1H), 8.32 (d, J=8.7 Hz, 1H), 8.26 (d, J=2.4 Hz, 1H), 8.10 (t, J=7.7 Hz, 1H), 7.92 (s, 1H), 7.78 (dd, J=8.1, 0.8 Hz, 1H), 7.47-7.41 (m, 1H), 5.79-5.71 (m, 1H), 5.08 (dq, J=10.1, 1.2 Hz, 1H), 4.97 (dq, J=17.0, 1.3 Hz, 1H), 4.77 (dt, J=6.2, 1.4 Hz, 2H), 3.99 (s, 1H), 2.75 (d, J=11.0 Hz, 1H), 2.52 (s, 6H), 2.32-2.18 (m, 1H), 2.09 (d, J=14.4 Hz, 4H), 1.31 (d, J=22.8 Hz, 4H); wherein, means that the cis-trans conformation is uncertain; scheme E: ##STR00284## (I-8-1), its .sup.1H NMR (400 MHz, CDCl.sub.3) has a peak of 1.23-1.08; wherein, means that the cis-trans conformation is uncertain; scheme F: ##STR00285## (I-1-1) with a retention time of 10.55 min under the following conditions: Agilent 1260 high performance liquid chromatograph; mobile phase A: water (0.1% formic acid), mobile phase B: acetonitrile; column time: 15 min; column type: Waters' Xselect, 5 μm, 4.6×250 mm; gradient elution, 5% mobile phase B.fwdarw.50% mobile phase B; ##STR00286## (I-1-2) with a retention time of 10.78 min under the following conditions: Agilent 1260 high performance liquid chromatograph; mobile phase A: water (0.1% formic acid), mobile phase B: acetonitrile; column time: 15 min; column type: Waters' Xselect, 5 μm, 4.6×250 mm; gradient elution, 5% mobile phase B.fwdarw.50% mobile phase B; ##STR00287## (I-3-1) with a retention time of 11.01 min under the following conditions: Agilent 1260 high performance liquid chromatograph; mobile phase A: water (0.1% formic acid), mobile phase B: acetonitrile; column time: 15 min; column type: Waters' Xselect, 5 μm, 4.6×250 mm; gradient elution, 5% mobile phase B.fwdarw.50% mobile phase B; ##STR00288## (I-3-2) with a retention time of 11.20 min under the following conditions: Agilent 1260 high performance liquid chromatograph; mobile phase A: water (0.1% formic acid), mobile phase B: acetonitrile; column time: 15 min; column type: Waters' Xselect, 5 μm, 4.6×250 mm; gradient elution, 5% mobile phase B.fwdarw.50% mobile phase B; ##STR00289## (I-8-1) with a retention time of 10.78 min under the following conditions: Agilent 1260 high performance liquid chromatograph; mobile phase A: water (0.1% formic acid), mobile phase B: acetonitrile; column time: 15 min; column type: Waters' Xselect, 5 μm, 4.6×250 mm; gradient elution, 5% mobile phase B.fwdarw.50% mobile phase B; ##STR00290## (I-8-2) with a retention time of 11.00 min under the following conditions: Agilent 1260 high performance liquid chromatograph; mobile phase A: water (0.1% formic acid), mobile phase B: acetonitrile; column time: 15 min; column type: Waters' Xselect, 5 μm, 4.6×250 mm; gradient elution, 5% mobile phase B.fwdarw.50% mobile phase B; ##STR00291## (I-15-1) with a retention time of 7.02 min under the following conditions: Agilent 1260 high performance liquid chromatograph; mobile phase A: water (0.1% formic acid), mobile phase B: acetonitrile; column time: 15 min; column type: Waters' Xselect, 5 μm, 4.6×250 mm; gradient elution, 5% mobile phase B.fwdarw.95% mobile phase B; ##STR00292## (I-15-2) with a retention time of 7.16 min under the following conditions: Agilent 1260 high performance liquid chromatograph; mobile phase A: water (0.1% formic acid), mobile phase B: acetonitrile; column time: 15 min; column type: Waters' Xselect, 5 μm, 4.6×250 mm; gradient elution, 5% mobile phase B.fwdarw.95% mobile phase B; ##STR00293## (I-36-1) with a retention time of 7.14 min under the following conditions: Agilent 1260 high performance liquid chromatograph; mobile phase A: water (0.1% formic acid), mobile phase B: acetonitrile; column time: 15 min; column type: Waters' Xselect, 5 μm, 4.6×250 mm; gradient elution, 5% mobile phase B.fwdarw.95% mobile phase B; ##STR00294## (I-36-2) with a retention time of 7.15 min under the following conditions: Agilent 1260 high performance liquid chromatograph; mobile phase A: water (0.1% formic acid), mobile phase B: acetonitrile; column time: 15 min; column type: Waters' Xselect, 5 μm, 4.6×250 mm; gradient elution, 5% mobile phase B-95% mobile phase B; ##STR00295## (I-41-1) with a retention time of 6.17 min under the following conditions: Agilent 1260 high performance liquid chromatograph; mobile phase A: water (0.1% formic acid), mobile phase B: acetonitrile; column time: 15 min; column type: Waters' Xselect, 5 μm, 4.6×250 mm; gradient elution, 5% mobile phase B.fwdarw.95% mobile phase B; ##STR00296## (I-41-2) with a retention time of 6.28 min under the following conditions: Agilent 1260 high performance liquid chromatograph; mobile phase A: water (0.1% formic acid), mobile phase B: acetonitrile; column time: 15 min; column type: Waters' Xselect, 5 μm, 4.6×250 mm; gradient elution, 5% mobile phase B.fwdarw.95% mobile phase B; wherein, means that the cis-trans conformation is uncertain; scheme G: ##STR00297## ##STR00298## ##STR00299## ##STR00300##

13. A preparation method of the pyrazolone-fused pyrimidine compound represented by formula II according to claim 1, the method is any of the following methods: method 1, comprising the following steps: step I, oxidizing compound II-1A by an oxidant in an organic solvent to obtain compound II-1B; step II, reacting compound II-1B with compound II-1C in an organic solvent and under alkaline conditions to obtain compound II; ##STR00301## method 2, comprising the following steps: step I, hydrolyzing compound II-2A (R.sup.1 is —(C═O)—O—C.sub.2H.sub.5) to obtain compound II-2B (R.sup.1 is —(C═O)—OH); step II, a condensation reaction is carried out between compound II-2B and an amino compound in an organic solvent to obtain compound II (R.sup.1 is —(C═O)—NR.sup.1-5-1R.sup.1-5-2); ##STR00302##

14. A compound represented by formula II-1C: ##STR00303## wherein, X is CH or N, A is as defined in claim 1.

15. A compound represented by formula II-1C: ##STR00304## wherein, X is CH or N, A is as defined in claim 1; the compound represented by formula II-1C is a compound represented by formula 1C: ##STR00305## wherein, A is C.sub.3-C.sub.20 cycloalkyl substituted by one R.sup.1, R.sup.1 is —NR.sup.1-3R.sup.1-4 or —C(═O)R.sup.1-5, and R.sup.1-3, R.sup.1-4 and R.sup.1-5 are as defined above.

16. The compound represented by formula II-1C according to claim 14, wherein, the compound is any one of the compounds described in any of the following schemes: scheme a: ##STR00306## scheme b: ##STR00307## its .sup.1H NMR (400 MHz, CDCl.sub.3) is δ 7.08-6.96 (m, 2H), 6.70-6.60 (m, 2H), 3.57 (s, 2H), 3.22 (t, J=7.0 Hz, 4H), 2.38 (tt, J=12.1, 3.2 Hz, 1H), 2.15-1.95 (m, 5H), 1.95-1.81 (m, 4H), 1.51-1.30 (m, 2H), 1.21-1.04 (m, 2H); or, ##STR00308## its .sup.1H NMR (400 MHz, MeOD) is δ 7.10-6.97 (m, 2H), 6.74-6.63 (m, 2H), 4.22-4.08 (t, J=8.0 Hz, 4H), 3.47-3.38 (m, 1H), 2.61-2.52 (m, 1H), 2.52-2.28 (m, 2H), 1.92-1.62 (m, 8H).

17. A method for inhibiting WEE1 kinase in a subject, comprising administering a therapeutically effective amount of a substance X to the subject; the substance X is the pyrazolone-fused pyrimidine compound represented by formula II according to claim 1, the pharmaceutically acceptable salt thereof, the solvate thereof, the solvate of the pharmaceutically acceptable salt thereof, the metabolite thereof or the prodrug thereof.

18. A pharmaceutical composition comprising the substance X and a pharmaceutical excipient; the substance X is the pyrazolone-fused pyrimidine compound represented by formula II according to claim 1, the pharmaceutically acceptable salt thereof, the solvate thereof, the solvate of the pharmaceutically acceptable salt thereof, the metabolite thereof or the prodrug thereof.

19. A combination comprising a substance X and an anticancer drug, the substance X is the pyrazolone-fused pyrimidine compound represented by formula II according to claim 1, the pharmaceutically acceptable salt thereof, the solvate thereof, the solvate of the pharmaceutically acceptable salt thereof, the metabolite thereof or the prodrug thereof.

20-24. (canceled)

25. A method for treating and/or preventing diseases or cancers related to WEE1 kinase comprising administering a therapeutically effective amount of the substance X to a patient; the substance X is the pyrazolone-fused pyrimidine compound represented by formula II according to claim 1, the pharmaceutically acceptable salt thereof, the solvate thereof, the solvate of the pharmaceutically acceptable salt thereof, the metabolite thereof or the prodrug thereof.

26. (canceled)

Description

DETAILED DESCRIPTION OF THE EMBODIMENT

[0634] The present disclosure will be further illustrated by way of embodiments below, but it is not limited to the scope of the embodiments. The experimental methods not specified in the specific conditions in the following embodiments are selected according to the conventional methods and conditions, or according to the commodity specifications.

[0635] The structures of all compounds of the present disclosure can be identified by nuclear magnetic resonance (.sup.1HNMR) and/or mass spectrometry (MS).

[0636] .sup.1H NMR chemical shift (6) was recorded in PPM (10.sup.−6). NMR was performed by Bruker AVANCE-400 spectrometer.

[0637] LC-MS was determined by Agilent 1200HPLC/6120 mass spectrometer.

[0638] HPLC was determined by Agilent 1260 high performance liquid chromatograph. Specific conditions of HPLC: mobile phase A: water (0.1% formic acid), mobile phase B: acetonitrile; column time: 15 min; column type: Waters' Xselect, 5 μm, 4.6×250 mm.

[0639] The thin layer silica gel plate was Liangchen silicon source HSGF254 or Qingdao GF254 silica gel plate. Column chromatography generally uses Yantai Huanghai 200-300 mesh silica gel as carrier.

Embodiment 1

[0640] ##STR00157## ##STR00158##

[0641] Step 1:

[0642] 4-Bromoaniline (I-1-a) (58.1 mmol) was dissolved in toluene (250 mL); potassium carbonate (87.2 mmol) and benzyl chloroformate (87.2 mmol) were added to the reaction mixture, and the reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was filtered, the filtrate was evaporated to dryness to obtain a crude product, and the crude product was washed with ethyl acetate to obtain the target compound benzyl (4-bromophenyl)carbamate (I-1-b)(15.2 g, 85.4%) as a gray solid. LC-MS: m/z: (M+H).sup.+=307.0.

[0643] Step 2:

[0644] Benzyl (4-bromophenyl)carbamate (16.0 mmol) (I-1-b) was dissolved in 1,2-dimethoxyethane (50 mL); and 4,4,5,5-tetramethyl-2-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)-1,3,2-dioxaborolane (represented by formula I-1-c) (16.0 mmol), sodium carbonate (42.0 mmol) and tetrakis(triphenylphosphine)palladium (1.6 mmol) were added to the reaction mixture, the reaction mixture was heated to 80° C. and stirred for 16 hours. The reaction mixture was filtered, the filtrate was evaporated to dryness to obtain a crude product, and the crude product was purified by column chromatography (dichloromethane/methanol=100/0-95/5) to obtain the target compound benzyl (4-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)phenyl)carbamate (I-1-d) (5.6 g, 94%) as a white solid. LC-MS: m/z: (M+H).sup.+=366.2.

[0645] Step 3:

[0646] Benzyl (4-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)phenyl)carbamate (I-1-d) (15 mmol) was dissolved in tetrahydrofuran (15 mL). Hydrochloric acid (30.0 mL, 4N) was added to the reaction mixture, and the reaction mixture was stirred at 50° C. for 16 hours. The pH value of the reaction mixture was adjusted to 9 with potassium carbonate, then the mixture was extracted with dichloromethane, the organic phase was washed with saturated saline, dried over anhydrous sodium sulfate, filtered and evaporated to dryness to obtain the crude target compound benzyl (4′-oxo-2′,3′,4′,5′-tetrahydro-[1,1′-biphenyl]-4-yl)carbamate (I-1-e) (4.0 g, 81%) as a yellow solid. LC-MS: m/z: (M+H).sup.+=322.1.

[0647] Step 4:

[0648] Benzyl (4′-oxo-2′,3′,4′,5′-tetrahydro-[1,1′-biphenyl]-4-yl)carbamate (I-1-e) (12.0 mmol) was dissolved in dichloromethane (25 mL), dimethylamine hydrochloride (25.0 mmol) and diisopropylethylamine (25.0 mmol) were added to the reaction mixture, and the reaction mixture was stirred at room temperature for 2 hours, and sodium triacetoxyborohydride (37.0 mmol) was added to the reaction mixture, then the reaction mixture was stirred at room temperature for 16 hours. The pH value of the mixture was adjusted to 9 by adding saturated potassium carbonate aqueous solution, and the mixture was extracted with dichloromethane; then the organic phase was washed with saturated saline, dried over anhydrous sodium sulfate, filtered and evaporated to dryness to obtain a crude product, and the crude product was purified by column chromatography (dichloromethane/methanol=100/0-95/5) to obtain the target compound benzyl (4′-(dimethylamino)-2′,3′,4′,5′-tetrahydro-[1,1′-biphenyl]-4-yl)carbamate (I-1-f) (3.5 g, 80%) as a yellow solid. LC-MS: m/z: (M+H).sup.+=351.2.

[0649] Step 5:

[0650] Benzyl (4′-(dimethylamino)-2′,3′,4′,5′-tetrahydro-[1,1′-biphenyl]-4-yl)carbamate (I-1-f) (10.0 mmol) was dissolved in methanol (20 mL), palladium carbon (0.35 g) was added thereto, and the reaction mixture was stirred under hydrogen at room temperature for 16 hours. The reaction mixture was filtered, and the filtrate was evaporated to dryness to obtain a crude product, the crude product was washed with ethyl acetate and filtered, and the filter cake was the target compound 4-(4-(dimethylamino)cyclohexyl)aniline (I-1-g)(1.20 g, 55%) as a white solid. LC-MS: m/z: (M+H).sup.+=219.2.

[0651] Step 6:

[0652] 2-(1,1-Difluoroallyl)-1-(6-(2-hydroxypropan-2-yl)pyridin-2-yl)-6-((4-(4-methylpiperazin-1-yl)phenyl)amino)-1,2-dihydro-3H-pyrazolo[3,4-d]pyrimidin-3-one (represented by formula I-1-h) (150 mg, 0.42 mmol) was dissolved in toluene (20 mL), 3-chlorophenoxyformic acid (105 mg, 0.47 mmol) was added thereto, and the reaction mixture was stirred at room temperature for 0.5 hours, then the reaction mixture was evaporated to dryness, the obtained sulfoxide intermediate was dissolved in dimethyl sulfoxide (10 mL); 4-(4-methylpiperazin-1-yl)aniline (120 mg, 0.55 mmol) and trifluoroacetic acid (0.2 mL) were added thereto, and the reaction mixture was heated to 60° C. and stirred for 24 hours. The pH value of the reaction mixture was adjusted to 9 with saturated sodium carbonate solution, water (50 mL) and dichloromethane (50 mL) were added thereto, the phases were separated, and the organic phase was washed with saturated saline, dried over anhydrous sodium sulfate, filtered, evaporated to dryness, prepared and purified in liquid phase to obtain compound I-1-1 and compound I-1-2. Compound I-1-1: HPLC retention time (RT)=10.55 min (HPLC conditions: gradient elution, 5% mobile phase B.fwdarw.50% mobile phase B), the yield of the compound was 56% (110 mg) as a white solid: .sup.1H NMR (400 MHz, MeOD) δ 8.85 (s, 1H), 8.46 (s, 2H), 7.99 (t, J=7.9 Hz, 1H), 7.79 (d, J=8.0 Hz, 1H), 7.65 (dd, J=16.6, 8.1 Hz, 3H), 7.22 (d, J=8.6 Hz, 2H), 5.73 (ddt, J=16.3, 10.2, 6.1 Hz, 1H), 5.05 (dd, J=10.3, 1.1 Hz, 1H), 4.93 (dd, J=17.1, 1.3 Hz, 1H), 4.82 (d, J=6.1 Hz, 2H), 2.90 (s, 6H), 2.60 (d, J=8.4 Hz, 1H), 2.21 (s, 2H), 2.10 (d, J=10.6 Hz, 2H), 1.70 (d, J=11.4 Hz, 4H), 1.59 (s, 6H). LC-MS: m/z: (M+H).sup.+=528.3. Compound I-1-2: HPLC retention time (RT)=10.78 min (HPLC conditions: gradient elution, 5% mobile phase B.fwdarw.50% mobile phase B), the yield of the compound was 72% (160 mg) as a white solid: .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.86 (s, 1H), 8.54 (s, 1H), 7.95 (t, J=7.9 Hz, 1H), 7.75 (d, J=8.0 Hz, 1H), 7.59 (d, J=8.5 Hz, 2H), 7.43 (d, J=7.6 Hz, 1H), 7.32 (d, J=8.5 Hz, 2H), 5.72 (ddt, J=16.5, 10.3, 6.2 Hz, 1H), 5.06 (d, J=10.2 Hz, 1H), 4.95 (dd, J=17.1, 1.0 Hz, 1H), 4.75 (d, J=6.1 Hz, 2H), 3.05 (m, 1H), 2.93 (m, 1H), 2.68 (s, 6H), 2.32 (m, 2H), 1.84 (m, 6H), 1.60 (s, 6H). LC-MS: m/z: (M+H).sup.+=528.3.

Embodiment 3

[0653] ##STR00159##

[0654] Compound (I-3-1) and compound (I-3-2) can be synthesized by the same method as in embodiment 1 using cyclopentane as a raw material. The details were as follows:

##STR00160##

[0655] Step 1:

[0656] Sodium borohydride acetate (0.85 g, 4 mmol) was added to a mixture of tert-butyl (4′-oxo-2′,3′,4′,5′-tetrahydro-[1,1′-biphenyl]-4-yl)carbamate (0.46 g, 1.6 mmol) (1-8-c) and tetrahydropyrrole (0.28 g, 3.9 mmol) in 20 mL of dichloromethane, and the mixture was stirred overnight at room temperature; the reaction mixture was washed with saturated sodium carbonate aqueous solution (20 mL), water (2*10 mL) and saturated saline sequentially; the organic phase was dried over anhydrous sodium sulfate, and the residue was mixed with silica gel and passed through a column {7M ammonia methanol: (dichloromethane:ethyl acetate=12:2)=0-15%} to obtain compound I-3-a, 200 mg of white solid. The yield was 40%. LC-MS: m/z: (M+H).sup.+=343.

[0657] Step 2:

[0658] Tert-butyl (4′-(pyrrolidin-1-yl)-2′,3′,4′,5′-tetrahydro-[1,1′-biphenyl]-4-yl)carbamate (300 mg, 0.87 mmol) (I-3-a) and 10% palladium carbon (100 mg) were added to 30 mL of methanol, the reaction flask was ventilated three times with a hydrogen balloon, and the reaction mixture was stirred overnight at room temperature in a hydrogen atmosphere. The reaction mixture was filtered and evaporated to dryness to obtain a crude product, which was separated by thin layer chromatography silica gel plate {7M ammonia methanol: (dichloromethane:ethyl acetate=9:3)=1:12} to obtain compound I-3-2-b, 70 mg of white solid (Rf=0.7), and compound I-3-1-b, 90 mg of white solid (Rf=0.5). The total yield was 52%. LC-MS: m/z: (M+H).sup.+=345.

[0659] Step 3:

[0660] Tert-butyl (4-(4-(pyrrolidin-1-yl)cyclohexyl)phenyl)carbamate (I-3-2-b) (Rf=0.7) (70 mg, 0.2 mmol) was added to 2 mL of dichloromethane, then 2 mL of trifluoroacetic acid was added thereto, and the mixture was stirred at room temperature for 2 hours. After the reaction mixture was concentrated, a brown oil (I-3-2-c) was obtained, which was directly used for the next step. LC-MS: m/z: (M+H).sup.+=245.

[0661] Tert-butyl (4-(4-(pyrrolidin-1-yl)cyclohexyl)phenyl)carbamate (I-3-1-b) (Rf=0.5) (70 mg, 0.2 mmol) was added to 2 mL of dichloromethane, then 2 mL of trifluoroacetic acid was added thereto, and the mixture was stirred at room temperature for 2 hours. After the reaction mixture was concentrated, a brown oil (I-3-1-c) was obtained, which was directly used for the next step. LC-MS: m/z: (M+H).sup.+=245.

[0662] Step 4:

[0663] m-Chloroperoxybenzoic acid (66 mg, 0.326 mmol) was added to a solution of 2-allyl-1-(6-(2-hydroxypropan-2-yl)pyridin-2-yl)-6-(methylthio)-1,2-dihydro-3H-pyrazolo[3,4-d]pyrimidin-3-one (I-1-h) (90 mg, 0.25 mmol) in 10 mL of toluene, and the obtained mixture was stirred at room temperature for 1 hour. The above reaction mixture was concentrated, and then trifluoroacetate of 4-(4-(azetidin-1-yl) cyclohexyl)aniline (I-3-1-c) (0.26 mmol), 0.15 mL of trifluoroacetic acid and 3 mL of dimethyl sulfoxide were added thereto, and the mixture was stirred at 60° C. overnight. 2 ML of saturated sodium carbonate aqueous solution and 10 mL of water were added to the above reaction mixture, and the mixture was extracted three times with dichloromethane (3*10 mL); then the organic phase was combined, washed with 5 mL of water and 5 mL of saturated sodium chloride solution, respectively, dried over anhydrous sodium sulfate, and concentrated to obtain a crude product; the crude product was separated by thin layer chromatography plate {7M ammonia methanol: (dichloromethane:ethyl acetate=5:1)=1:12} to obtain compound I-3-1, 40 mg of white solid (Rf=0.4), the yield was 28%. Compound 1-3-1: HPLC retention time (RT)=11.01 min (HPLC conditions: mobile phase A was water (containing 0.1% HCOOH), mobile phase B was acetonitrile; gradient elution: 5% mobile phase B.fwdarw.50% mobile phase B), .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.87 (s, 1H), 7.90 (t, J=7.9 Hz, 1H), 7.78 (d, J=8.0 Hz, 1H), 7.53 (d, J=8.5 Hz, 2H), 7.39 (dd, J=7.6, 0.5 Hz, 1H), 7.20 (d, J=8.5 Hz, 2H), 5.72 (ddt, J=16.4, 10.2, 6.2 Hz, 1H), 5.06 (dd, J=10.2, 1.0 Hz, 1H), 4.95 (dd, J=17.1, 1.2 Hz, 1H), 4.76 (d, J=6.2 Hz, 2H), 4.04 (s, 1H), 2.66 (m, 4H), 2.58-2.47 (m, 1H), 2.16 (m, 4H), 1.96 (m, 2H), 1.87-1.78 (m, 4H), 1.60 (s, 6H), 1.58-1.39 (m, 4H). LC-MS: m/z: (M+H).sup.+=554.

[0664] m-Chloroperoxybenzoic acid (60 mg, 0.296 mmol) was added to a solution of 2-allyl-1-(6-(2-hydroxypropan-2-yl)pyridin-2-yl)-6-(methylthio)-1,2-dihydro-3H-pyrazolo[3,4-d]pyrimidin-3-one (I-1-h) (80 mg, 0.22 mmol) in 10 mL of toluene, and the obtained mixture was stirred at room temperature for 1 hour. The above reaction mixture was concentrated, and then trifluoroacetate of 4-(4-(azetidin-1-yl) cyclohexyl)aniline (I-3-2-c) (0.2 mmol), 0.15 mL of trifluoroacetic acid and 3 mL of dimethyl sulfoxide were added thereto, and the mixture was stirred at 60° C. overnight. 2 ML of saturated sodium carbonate aqueous solution and 10 mL of water were added to the above reaction mixture, and the mixture was extracted three times with dichloromethane (3*10 mL); then the organic phase was combined, washed with 5 mL of water and 5 mL of saturated sodium chloride solution, respectively, dried over anhydrous sodium sulfate, and concentrated to obtain a crude product; the crude product was separated by thin layer chromatography plate {7M ammonia methanol: (dichloromethane:ethyl acetate=5:1)=1:12} to obtain compound I-3-2, 50 mg of white solid (Rf=0.6), the yield was 40%. Compound 1-3-2: HPLC retention time (RT)=11.20 min (HPLC conditions: mobile phase A was water (containing 0.1% HCOOH), mobile phase B was acetonitrile; gradient elution: 5% mobile phase B.fwdarw.50% mobile phase B), .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.87 (s, 1H), 7.92 (t, J=7.9 Hz, 1H), 7.80 (d, J=8.0 Hz, 1H), 7.52 (d, J=8.5 Hz, 2H), 7.38 (d, J=7.6 Hz, 1H), 7.29 (t, J=4.2 Hz, 2H), 5.79-5.66 (m, 1H), 5.06 (dd, J=10.2, 1.0 Hz, 1H), 4.96 (dd, J=17.1, 1.2 Hz, 1H), 4.77 (d, J=6.2 Hz, 2H), 4.02 (s, 1H), 2.70-2.50 (m, 5H), 2.26 (s, 1H), 1.98 (m, 4H), 1.82 (s, 4H), 1.69-1.56 (m, 10H). LC-MS: m/z: (M+H).sup.+=554.

Embodiment 4

[0665] ##STR00161##

[0666] Step 1:

[0667] 1-Bromo-4-nitrobenzene (I-4-a) (692 mg, 3.43 mmol), ethyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclohex-3-ene-1-carboxylate (I-4-b) (800 mg, 2.85 mmol), tetrakis(triphenylphosphine)palladium (330 mg, 0.286 mmol), triphenylphosphine (75 mg, 0.286 mmol) and potassium carbonate (789 mg, 5.71 mmol) were dissolved in 1,4-dioxane (20 mL), the mixture was heated to 90° C. under the protection of argon and stirred for about 16 hours. Then the reaction mixture was concentrated and purified by column chromatography (silica gel, petroleum ether/ethyl acetate=100% to 90%) to obtain 450 mg of the compound represented by formula I-4-c as a white solid. Yield: 47%. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.23-8.16 (m, 2H), 7.57-7.49 (m, 2H), 6.33 (dd, J=5.1, 2.8 Hz, 1H), 4.26-4.15 (m, 2H), 2.72-2.61 (m, 1H), 2.59-2.51 (m, 4H), 2.24 (ddd, J=9.3, 8.0, 3.9 Hz, 1H), 1.90 (dddd, J=13.1, 11.0, 8.8, 6.7 Hz, 1H), 1.31 (dd, J=9.2, 5.1 Hz, 3H).

[0668] Step 2:

[0669] Ethyl 4-(4-nitrophenyl)cyclohex-3-ene-1-carboxylate (I-4-c) (450 mg, 1.63 mmol) was dissolved in methanol (10 mL), palladium/carbon catalyst (45 mg, 10%) was added thereto, and the mixture was stirred at room temperature for about 2 days under hydrogen atmosphere, filtered, the filtrate was concentrated and purified by column chromatography (silica gel, petroleum ether/ethyl acetate=100% to 90%) to obtain 280 mg of the compound represented by formula I-4-d as a white solid. Yield: 69%. LC-MS: m/z: (M+H).sup.+=248.4.

[0670] Step 3:

[0671] 2-Allyl-1-[6-(1-hydroxy-1-methyl-ethyl)-2-pyridyl]-6-methylthiopyrazolo[3,4-d]pyrimidin-3-one (I-1-h) (428 mg, 1.20 mmol) was dissolved in toluene (20 mL), m-chloroperoxybenzoic acid (259 mg, 1.5 mmol) was added thereto, the mixture was stirred at room temperature for about 1 hour, then ethyl 4-(4-aminophenyl)cyclohexane carboxylate (247 mg, 1.0 mmol) and DIPEA (258 mg, 2.0 mmol) were added thereto, and the mixture was heated to 90° C. and stirred for about 16 hours. The reaction mixture was concentrated and purified by column chromatography (silica gel, dichloromethane/methanol=100% to 90%), preparative high performance liquid phase, and thin layer chromatography (DCM/CH.sub.3OH/NH.sub.3 CH.sub.3OH=10/1/0.15) to obtain 440 mg of the compound represented by formula I-4 as a white solid, yield: 79%. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.87 (d, J=2.1 Hz, 1H), 7.91 (td, J=7.9, 1.5 Hz, 1H), 7.78 (d, J=8.0 Hz, 1H), 7.54 (t, J=7.9 Hz, 2H), 7.39 (d, J=7.7 Hz, 1H), 7.21 (d, J=8.5 Hz, 2H), 5.72 (ddt, J=16.4, 10.2, 6.2 Hz, 1H), 5.07 (dd, J=10.2, 1.1 Hz, 1H), 4.96 (dd, J=17.1, 1.2 Hz, 1H), 4.77 (d, J=6.2 Hz, 2H), 4.25-4.10 (m, 2H), 3.95 (s, 1H), 2.73 (s, 1H), 2.56 (dt, J=15.5, 10.8 Hz, 1H), 2.28 (d, J=7.9 Hz, 1H), 2.14 (d, J=10.6 Hz, 1H), 2.05-1.97 (m, 1H), 1.78 (dd, J=19.0, 8.5 Hz, 1H), 1.67 (dt, J=10.1, 6.1 Hz, 3H), 1.61 (s, 6H), 1.59-1.44 (m, 1H), 1.34-1.26 (m, 3H). LC-MS: m/z: (M+H).sup.+=557.4.

Embodiment 5

[0672] ##STR00162##

[0673] 4-[4-[[2-Allyl-1-[6-(1-hydroxy-1-methyl-ethyl)-2-pyridyl]-3-oxo-pyrazolo[3,4-d]pyrimidin-6-ethyl[amino]phenyl]cyclohexane carboxylate (I-4) (420 mg, 0.75 mmol) was dissolved in methanol (20 mL), 2N sodium hydroxide aqueous solution (10 mL) was added, the mixture was stirred at room temperature for about 3 days, concentrated to remove methanol, extracted with dichloromethane, then the organic layer was discarded, and the pH value was adjusted to 4 by adding 1N hydrochloric acid aqueous solution to the aqueous layer, then the the aqueous layer was extracted with dichloromethane; and the organic layer was dried over anhydrous sodium sulfate, concentrated, purified by column chromatography (silica gel, dichloromethane/methanol=100% to 95%) to obtain 256 mg of the compound represented by formula I-5 as a white solid, yield: 64%. .sup.1H NMR (400 MHz, MeOD) δ 8.84 (d, J=1.4 Hz, 1H), 8.00 (td, J=7.9, 4.0 Hz, 1H), 7.83-7.76 (m, 1H), 7.67 (dd, J=7.7, 0.7 Hz, 1H), 7.60 (dd, J=8.4, 5.7 Hz, 2H), 7.19 (dd, J=13.2, 8.6 Hz, 2H), 5.73 (ddd, J=17.0, 6.1, 4.1 Hz, 1H), 5.08-5.03 (m, 1H), 4.95 (d, J=1.3 Hz, 1H), 4.86-4.79 (m, 2H), 2.72 (s, 1H), 2.58 (s, 1H), 2.27 (d, J=6.7 Hz, 1H), 2.13 (d, J=10.0 Hz, 1H), 1.96 (d, J=10.2 Hz, 1H), 1.80-1.66 (m, 4H), 1.64-1.52 (m, 7H). LC-MS: m/z: (M+H).sup.+=529.3.

Embodiment 6

[0674] ##STR00163##

[0675] 40 mg (0.076 mmol) of 4-(4-((2-allyl-1-(6-(2-hydroxypropan-2-yl)pyridin-2-yl)-3-oxo-2,3-dihydro-1H-pyrazolo[3,4-d]pyrimidin-6-yl)amino)phenyl)cyclohexane-1-carboxylic acid (I-5) was dissolved in 5 mL of dichloromethane, and 9 mg (0.11 mol) of dimethylamine hydrochloride, 17 mg (0.11 mmol) of EDCI, 15 mg (0.11 mmol) of HOBt and 19 mg (0.15 mmol) of DIPEA were added thereto, and the mixture was stirred at room temperature for about 16 hours, and then purified by thin layer chromatography (DCM/CH3OH=100/10) to obtain 15 mg of a light yellow solid (I-6), the yield was 35%. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.86 (d, J=4.2 Hz, 1H), 7.97-7.88 (m, 1H), 7.79 (d, J=8.0 Hz, 1H), 7.53 (dd, J=12.3, 8.5 Hz, 2H), 7.39 (d, J=7.6 Hz, 1H), 7.28-7.15 (m, 2H), 5.80-5.65 (m, 1H), 5.06 (d, J=10.0 Hz, 1H), 4.95 (d, J=17.1 Hz, 1H), 4.77 (d, J=6.0 Hz, 2H), 3.10 (d, J=12.1 Hz, 3H), 2.98 (s, 3H), 2.67-2.57 (m, 1H), 2.14 (dd, J=20.9, 10.3 Hz, 1H), 2.06-1.97 (m, 2H), 1.92 (d, J=14.0 Hz, 1H), 1.78-1.66 (m, 4H), 1.61 (s, 6H), 1.49 (dd, J=22.8, 12.2 Hz, 1H). LC-MS: m/z: (M+H).sup.+=556.3.

Embodiment 7

[0676] ##STR00164##

[0677] 40 mg (0.076 mmol) of 4-(4-((2-allyl-1-(6-(2-hydroxypropan-2-yl)pyridin-2-yl)-3-oxo-2,3-dihydro-1H-pyrazolo[3,4-d]pyrimidin-6-yl)amino)phenyl)cyclohexane-1-carboxylic acid (I-5) was dissolved in 5 mL of dichloromethane, and 9 mg (0.11 mol) of azetidine hydrochloride (I-7-a), 17 mg (0.11 mmol) of EDCI, 15 mg (0.11 mmol) of HOBt and 19 mg (0.15 mmol) of DIPEA were added thereto, and the mixture was stirred at room temperature for about 16 hours, and then purified by thin layer chromatography (DCM/CH3OH=100/10) to obtain 15 mg of a light yellow solid (I-7), the yield was 35%. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.85 (d, J=4.7 Hz, 1H), 7.91 (dt, J=10.7, 7.9 Hz, 1H), 7.78 (d, J=7.8 Hz, 1H), 7.53 (dd, J=12.0, 8.5 Hz, 2H), 7.39 (dd, J=7.6, 2.4 Hz, 1H), 7.22 (dd, J=19.5, 8.5 Hz, 2H), 5.71 (ddt, J=16.4, 10.2, 6.2 Hz, 1H), 5.06 (d, J=10.2 Hz, 1H), 4.95 (d, J=17.1 Hz, 1H), 4.77 (d, J=6.1 Hz, 2H), 4.21 (dd, J=16.4, 8.6 Hz, 2H), 4.10-4.02 (m, 2H), 2.63-2.52 (m, 2H), 2.35-2.20 (m, 2H), 2.15-2.07 (m, 1H), 2.00 (dd, J=13.4, 3.0 Hz, 2H), 1.92-1.83 (m, 1H), 1.79-1.63 (m, 4H), 1.60 (s, 6H), 1.48 (ddd, J=24.7, 12.5, 2.5 Hz, 1H). LC-MS: m/z: (M+H).sup.+=568.4.

Embodiment 8

[0678] ##STR00165## ##STR00166## ##STR00167##

[0679] Step 1:

[0680] 4,4,5,5-Tetramethyl-2-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)-1,3,2-dioxaborolane (I-1-c) (19 g, 71.4 mmol), tert-butyl (4-bromophenyl)carbamate (I-8-a) (18.4 g, 67.6 mmol), 2 mol/L sodium carbonate aqueous solution (75 mL) and Pd(dppf)Cl.sub.2 (3.3 g, 4.5 mmol) were added to 250 mL of 1,4-dioxane, and the reaction flask was ventilated with a nitrogen balloon for three times, and the mixture was stirred at 98° C. overnight. The reaction mixture was filtered and concentrated, and the aqueous phase was extracted with ethyl acetate (2*100 mL), the combined organic phase was washed with saturated saline, dried over anhydrous sodium sulfate and concentrated to obtain a crude product, which was purified by column (ethyl acetate:petroleum ether=0-40%) to obtain 19 g of a brown solid (I-8-b). The yield was 84.8%. LC-MS: m/z: (M-56+H).sup.+=276.

[0681] Step 2:

[0682] 1.38 Mol/L hydrochloric acid (160 mL) was added to a solution of tert-butyl (4-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)phenyl)carbamate (I-8-b) (16 g, 48 mmol) in 100 mL of tetrahydrofuran, and the mixture was stirred at room temperature overnight. Then the mixture was extracted with ethyl acetate (2*150 mL), the combined organic phase was washed three times with saturated saline, and the organic phase was dried over anhydrous sodium sulfate and concentrated to obtain 13.5 g of a yellow-brown solid (I-8-c), which was directly used for the next step. The yield was 97%. LC-MS: m/z: (M-56+H).sup.+=232.

[0683] Step 3:

[0684] N,N′-diisopropylethylamine (12 mL, 69 mmol) and sodium borohydride acetate (14 g, 71 mmol) were added to a mixture of tert-butyl (4′-oxo-2′,3′,4′,5′-tetrahydro-[1,1′-biphenyl]-4-yl)carbamate (I-8-c) (10 g, 34.8 mmol) and azetidine hydrochloride (3 g, 32 mmol) in 100 mL of dichloromethane, and the mixture was stirred at room temperature overnight; then the solvent was evaporated, and 100 mL of dichloromethane was added thereto, and the mixture was washed with saturated sodium carbonate aqueous solution (20 mL), water (2*30 mL) and saturated saline sequentially; then the organic phase was dried over anhydrous sodium sulfate and then mixed with silica gel and passed through the column {7M ammonia methanol:(dichloromethane:ethyl acetate=15:1)=0-15%} to obtain 7.3 g of white solid (I-8-d). The yield was 64%. LC-MS: m/z: (M+H).sup.+=329.

[0685] Step 4:

[0686] Tert-butyl (4′-(azetidin-1-yl)-2′,3′,4′,5′-tetrahydro-[1,1′-biphenyl]-4-yl)carbamate (I-8-d) (7.3 g, 22 mmol) and 10% palladium carbon (200 mg) were added to 150 mL of methanol, the reaction flask was ventilated three times with a hydrogen balloon, and the reaction mixture was stirred overnight at room temperature in a hydrogen atmosphere. The reaction mixture was filtered and evaporated to dryness to obtain a crude product, the crude product was washed with ethyl acetate and filtered, and the filter cake was 4.1 g of compound I-8-e (Rf=0.4) as a white solid. The total yield was 85%. LC-MS: m/z: (M+H).sup.+=331.

[0687] Step 5:

[0688] Tert-butyl (4-(4-(azetidin-1-yl)cyclohexyl)phenyl)carbamate (3 g, 9 mmol) (represented by formula I-8-e) was added to 20 mL of dichloromethane, then 20 mL of trifluoroacetic acid was added thereto, and the mixture was stirred at room temperature for 2 hours. After the reaction mixture was concentrated, 10 mL of water and 20 mL of saturated sodium carbonate solution were added thereto, and the formed solid was filtered, washed with water and drained to obtain 1.8 g of compound I-8-f as a brown solid, which was directly used in the next step. The yield was 86%. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.08-6.96 (m, 2H), 6.70-6.60 (m, 2H), 3.57 (s, 2H), 3.22 (t, J=7.0 Hz, 4H), 2.38 (tt, J=12.1, 3.2 Hz, 1H), 2.15-1.95 (m, 5H), 1.95-1.81 (m, 4H), 1.51-1.30 (m, 2H), 1.21-1.04 (m, 2H). LC-MS: m/z: (M+H).sup.+=231.

[0689] Step 6:

[0690] m-Chloroperoxybenzoic acid (1.33 g, 6.57 mmol) was added to a solution of 2-allyl-1-(6-(2-hydroxypropan-2-yl)pyridin-2-yl)-6-(methylthio)-1,2-dihydro-3H-pyrazolo[3,4-d]pyrimidin-3-one (1.86 g, 5.2 mmol) (represented by I-1-h) in 60 mL of toluene, and the obtained mixture was stirred at room temperature for 1 hour. The above reaction mixture was concentrated, and then 4-(4-(azetidin-1-yl)cyclohexyl)aniline (1.2 g, 5.2 mmol) (represented by I-8-f), 0.8 mL of trifluoroacetic acid and 20 mL of dimethyl sulfoxide were added thereto, and the mixture was stirred at 60° C. overnight. 20 ML of saturated sodium carbonate aqueous solution and 50 mL of water were added to the above reaction mixture, and the mixture was extracted three times with dichloromethane (3*150 mL); then the organic phase was combined, washed with 50 mL of water and 30 mL of saturated sodium chloride solution, respectively, dried over anhydrous sodium sulfate, and concentrated to obtain a crude product; the crude product was separated by thin layer chromatography plate {7M ammonia methanol: (dichloromethane:ethyl acetate=5:1)=1:12} to obtain compound I-8, 1.88 g of a white solid, the yield was 67%. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.86 (s, 1H), 7.93-7.85 (m, 1H), 7.78 (d, J=7.8 Hz, 1H), 7.52 (d, J=8.5 Hz, 2H), 7.39 (dd, J=7.6, 0.7 Hz, 1H), 7.19 (d, J=8.5 Hz, 2H), 5.71 (ddt, J=16.4, 10.2, 6.2 Hz, 1H), 5.05 (dd, J=10.2, 1.1 Hz, 1H), 4.94 (dd, J=17.1, 1.3 Hz, 1H), 4.77 (d, J=6.2 Hz, 2H), 4.11 (d, J=8.9 Hz, 1H), 3.24 (t, J=7.0 Hz, 4H), 2.52-2.43 (m, 1H), 2.14-2.00 (m, 3H), 1.92 (d, J=11.2 Hz, 4H), 1.60 (s, 6H), 1.45 (dt, J=14.9, 7.5 Hz, 2H), 1.23-1.08 (m, 2H). LC-MS: m/z: (M+H).sup.+=540.4.

Embodiment 8-1

[0691] The product of embodiment 8 (compound I-8) was detected by HPLC (conditions: mobile phase A was water (containing HCOOH 0.1%), mobile phase B was acetonitrile; gradient elution: 5% mobile phase B.fwdarw.50% mobile phase B) with the only retention time: HPLC retention time (RT)=10.78 min. Therefore, its cyclohexyl part was cis or trans, i.e., it was

##STR00168##

refers to cis or trans.

[0692] The reaction route was as follows:

##STR00169## ##STR00170##

Embodiment 8-2

[0693] ##STR00171##

[0694] 2-Allyl-1-(6-(2-hydroxypropan)pyridin-2-yl)-6-((4-(4-oxocyclohexyl)phenyl)amino)-1,2-dihydro-3H-pyrazolo[3,4-d]pyrimidin-3-one (I-19-d) (19.0 mmol) was dissolved in dichloromethane (500 mL), and azetidine hydrochloride (21.0 mmol), N-ethyl-N-isopropyl-2-amine (38.0 mmol) and sodium triacetoxyborohydride (57 mmol) were added to the reaction mixture, and the reaction mixture was stirred at 30° C. for 16 hours. Water (300 mL) and potassium carbonate were added to the reaction mixture, the pH value was adjusted to 9, and the mixture was extracted with dichloromethane; the organic phase was washed with saturated saline, dried over anhydrous magnesium sulfate, filtered, and the filtrate was evaporated to dryness to obtain a crude product, and the crude product was purified by column chromatography (dichloromethane/methanol=0/100-5/95) to obtain target compound I-8-1 (1.8 g, 24.7%) and target compound I-8-2 (4.7 g, 65.3%), both of which were white solids.

[0695] Compound I-8-1: HPLC: retention time (RT)=10.78 min (HPLC conditions: mobile phase A was water (containing HCOOH 0.1%), mobile phase B was acetonitrile; gradient elution: 5% mobile phase B.fwdarw.50% mobile phase B), .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.86 (s, 1H), 7.93-7.85 (m, 1H), 7.78 (d, J=7.8 Hz, 1H), 7.52 (d, J=8.5 Hz, 2H), 7.39 (dd, J=7.6, 0.7 Hz, 1H), 7.19 (d, J=8.5 Hz, 2H), 5.71 (ddt, J=16.4, 10.2, 6.2 Hz, 1H), 5.05 (dd, J=10.2, 1.1 Hz, 1H), 4.94 (dd, J=17.1, 1.3 Hz, 1H), 4.77 (d, J=6.2 Hz, 2H), 4.11 (d, J=8.9 Hz, 1H), 3.24 (t, J=7.0 Hz, 4H), 2.52-2.43 (m, 1H), 2.14-2.00 (m, 3H), 1.92 (d, J=11.2 Hz, 4H), 1.60 (s, 6H), 1.45 (dt, J=14.9, 7.5 Hz, 2H), 1.23-1.08 (m, 2H). LC-MS: m/z: (M+H).sup.+=540.4.

[0696] Compound I-8-2: HPLC: retention time (RT)=11.00 min (HPLC conditions: mobile phase A was water (containing HCOOH 0.1%), mobile phase B was acetonitrile; gradient elution: 5% mobile phase B.fwdarw.50% mobile phase B), .sup.1H NMR (400 MHz, CDCl.sub.3) δ8.87 (s, 1H), 7.92 (d, J=7.8 Hz, 1H), 7.80 (d, J=8.0 Hz, 1H), 7.52 (d, J=8.4 Hz, 2H), 7.39 (d, J=7.6 Hz, 1H), 7.29-7.25 (m, 2H), 5.82-5.63 (m, 1H), 5.12-4.91 (m, 2H), 4.78 (d, J=6.2 Hz, 2H), 4.01 (s, 1H), 3.17 (s, 4H), 2.53 (s, 1H), 2.33 (s, 1H), 2.06 (d, J=4.4 Hz, 2H), 1.89 (d, J=11.6 Hz, 2H), 1.75 (d, J=14.1 Hz, 2H), 1.59 (d, J=17.2 Hz, 8H), 1.46 (t, J=13.1 Hz, 2H). LC-MS: 540.0[M+1].sup.+.

[0697] It can be seen that there was a big difference between the cis- and trans-configuration hydrogen spectrum data, which was enough to distinguish them.

Embodiment 8-3

[0698] ##STR00172##

[0699] Step 1:

[0700] Tert-butyl (4′-(azetidin-1-yl)-2′,3′,4′,5′-tetrahydro-[1,1′-biphenyl]-4-yl)carbamate (I-8-d) (7.3 g, 22 mmol) and 10% palladium carbon (200 mg) were added to 150 mL of methanol, the reaction flask was ventilated three times with a hydrogen balloon, and the reaction mixture was stirred overnight at room temperature in a hydrogen atmosphere. The reaction mixture was filtered and evaporated to dryness to obtain a crude product, which was mixed with silica gel and passed through the column {7 M ammonia methanol:(dichloromethane:ethyl acetate=12:3)=0-15%} to obtain 2.1 g of compound I-8-e″ (Rf=0.6) as a white solid and 4.1 g of compound I-8-e′ as a white solid (Rf=0.4). The total yield was 85%. LC-MS: m/z: (M+H).sup.+=331.

[0701] Step 2:

[0702] Tert-butyl (4-(4-(azetidin-1-yl)cyclohexyl)phenyl)carbamate (2 g, 9 mmol) (represented by formula I-8-e″) was added to 20 mL of dichloromethane, then 20 mL of trifluoroacetic acid was added thereto, and the mixture was stirred at room temperature for 2 hours. After the reaction mixture was concentrated, 10 mL of water and 20 mL of saturated sodium carbonate solution were added thereto, and the formed solid was filtered, washed with water and drained to obtain 1.2 g of compound I-8-f″ as a brown solid, which was directly used in the next step. The yield was 86%. .sup.1H NMR (400 MHz, MeOD) δ 7.10-6.97 (m, 2H), 6.74-6.63 (m, 2H), 4.22-4.08 (t, J=8.0 Hz, 4H), 3.47-3.38 (m, 1H), 2.61-2.52 (m, 1H), 2.52-2.28 (m, 2H), 1.92-1.62 (m, 8H). LC-MS: m/z: (M+H).sup.+=231.

[0703] Step 3:

[0704] m-Chloroperoxybenzoic acid (1.33 g, 6.57 mmol) was added to a solution of 2-allyl-1-(6-(2-hydroxypropan-2-yl)pyridin-2-yl)-6-(methylthio)-1,2-dihydro-3H-pyrazolo[3,4-d]pyrimidin-3-one (1.86 g, 5.2 mmol) (represented by I-1-h) in 60 mL of toluene, and the obtained mixture was stirred at room temperature for 1 hour. The above reaction mixture was concentrated, and then 4-(4-(azetidin-1-yl)cyclohexyl)aniline (1.2 g, 5.2 mmol) (represented by I-8-f″), 0.8 mL of trifluoroacetic acid and 20 mL of dimethyl sulfoxide were added thereto, and the mixture was stirred at 60° C. overnight. 20 ML of saturated sodium carbonate aqueous solution and 50 mL of water were added to the above reaction mixture, and the mixture was extracted three times with dichloromethane (3*150 mL); then the organic phase was combined, washed with 50 mL of water and 30 mL of saturated sodium chloride solution, respectively, dried over anhydrous sodium sulfate, and concentrated to obtain a crude product; the crude product was separated by thin layer chromatography plate {7M ammonia methanol: (dichloromethane:ethyl acetate=5:1)=1:12} to obtain compound I-8-2, 1.88 g of a white solid, the yield was 67%. .sup.1H NMR (400 MHz, CDCl.sub.3) δ8.87 (s, 1H), 7.92 (d, J=7.8 Hz, 1H), 7.80 (d, J=8.0 Hz, 1H), 7.52 (d, J=8.4 Hz, 2H), 7.39 (d, J=7.6 Hz, 1H), 7.29-7.25 (m, 2H), 5.82-5.63 (m, 1H), 5.12-4.91 (m, 2H), 4.78 (d, J=6.2 Hz, 2H), 4.01 (s, 1H), 3.17 (s, 4H), 2.53 (s, 1H), 2.33 (s, 1H), 2.06 (d, J=4.4 Hz, 2H), 1.89 (d, J=11.6 Hz, 2H), 1.75 (d, J=14.1 Hz, 2H), 1.59 (d, J=17.2 Hz, 8H), 1.46 (t, J=13.1 Hz, 2H). LC-MS: m/z: (M+H).sup.+=540.

Embodiment 15

[0705] ##STR00173## ##STR00174##

[0706] Step 1:

[0707] 1 g (4.22 mmol) of 2,6-dibromopyridine (I-15-a) was dissolved in 30 mL of dichloromethane, the mixture was cooled to −78° C., and 1.86 mL (4.64 mmol, 2M solution of dioxane) of n-butyllithium solution was slowly added dropwise, after the mixture was stirred for about 15 min, and 0.3 g (4.22 mmol) of oxetan-3-one (represented by formula I-15-b) was added thereto, the stirring was continued for about 1 hour; and the mixture was quenched with saturated ammonium chloride aqueous solution, and then extracted with dichloromethane, the organic layer was dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography (petroleum ether/ethyl acetate=100% to 50%) to obtain 660 mg of 3-(6-bromo-2-pyridyl)oxetan-3-ol (I-15-c) as a white solid, the yield was 68%. LC-MS: m/z: (M+H).sup.+=230.1.

[0708] Step 2:

[0709] 106 mg (0.48 mmol) of 2-allyl-6-methylthio-1H-pyrazolo[3,4-d]pyrimidin-3-one (I-15-d) and 100 mg (0.43 mmol) of 3-(6-bromo-2-pyridyl)oxetan-3-ol (I-15-c) were dissolved into 10 mL of 1,4-dioxane, and then 90 mg (0.65 mmol) of potassium carbonate, 83 mg (0.43 mmol) of cuprous iodide and 77 mg (0.87 mmol) of N1,N2-dimethylethyl-1,2-diamine were added thereto, and the mixture was heated to 100° C. under the protection of argon and stirred overnight. The residue was concentrated and purified by silica gel column chromatography (UV, dichloromethane/methanol=100% to 10%) to obtain 140 mg of 2-allyl-1-[6-(3-hydroxyoxetan-3-yl)-2-pyridinyl]-6-methylthiopyrazolo[3,4-d]pyrimidin-3-one (I-15-e) as a brown oil, the yield was 86%. LC-MS: m/z: (M+H).sup.+=372.1.

[0710] Step 3:

[0711] 549 mg (1.478 mmol) of 2-allyl-1-[6-(3-hydroxyoxetan-3-yl)-2-pyridinyl]-6-methylthiopyrazolo[3,4-d]pyrimidin-3-one (represented by I-15-e) was dissolved in 30 mL of toluene, 397 mg (1.7714 mmol) of 3-chloroperoxybenzoic acid was added thereto, and the mixture was stirred at room temperature for about 1 hour, then 354 mg (1.622 mmol) of 4-(4-(dimethylamino)cyclohexyl)aniline (I-1-f) and 381 mg (2.9480 mmol) of DIPEA were added thereto, and the reaction mixture was concentrated and purified by thin layer chromatography (dichloromethane/methanol/methanol solution of ammonia=25/1/0.15) to obtain compound I-15-1 and compound I-15-2. Compound I-15-1: HPLC retention time (RT)=7.02 min (HPLC conditions: gradient elution, 5% mobile phase B.fwdarw.95% mobile phase B), the yield of the compound was 10% (80 mg) as a white solid; .sup.1H NMR (400 MHz, MeOD) δ 8.84 (s, 1H), 8.04 (t, J=7.9 Hz, 1H), 7.92 (d, J=8.1 Hz, 1H), 7.67 (d, J=7.6 Hz, 1H), 7.60 (d, J=8.6 Hz, 2H), 7.21 (d, J=8.6 Hz, 2H), 5.78 (ddt, J=16.3, 10.3, 6.1 Hz, 1H), 5.12-5.05 (m, 3H), 4.98 (dd, J=17.1, 1.3 Hz, 1H), 4.89 (d, J=6.1 Hz, 2H), 4.84 (s, 2H), 3.68 (s, 2H), 2.97-2.86 (m, 1H), 2.66 (s, 6H), 2.60-2.50 (m, 1H), 2.15 (d, J=8.6 Hz, 2H), 2.04 (d, J=9.0 Hz, 2H), 1.66-1.54 (m, 4H). LC-MS: m/z: (M+H).sup.+=542.4. Compound I-15-2: HPLC retention time (RT)=7.16 min (HPLC conditions: gradient elution, 5% mobile phase B.fwdarw.95% mobile phase B), the yield of the compound was 20% (160 mg) as a white solid: .sup.1H NMR (400 MHz, MeOD) δ 8.83 (s, 1H), 8.04 (t, J=7.9 Hz, 1H), 7.92 (d, J=8.0 Hz, 1H), 7.67-7.62 (m, 1H), 7.59 (d, J=8.6 Hz, 2H), 7.29 (d, J=8.5 Hz, 2H), 5.76 (ddt, J=16.3, 10.2, 6.1 Hz, 1H), 5.10-5.02 (m, 3H), 4.96 (dd, J=17.1, 1.3 Hz, 1H), 4.87 (d, J=6.8 Hz, 2H), 4.82 (d, J=6.8 Hz, 2H), 2.73 (d, J=4.2 Hz, 1H), 2.29 (d, J=21.9 Hz, 7H), 2.04-1.90 (m, 4H), 1.66 (dd, J=15.6, 6.1 Hz, 4H). LC-MS: m/z: (M+H).sup.+=542.3.

Embodiment 19

[0712] ##STR00175## ##STR00176##

[0713] Step 1:

[0714] 4,4,5,5-Tetramethyl-2-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)-1,3,2-dioxaborolane (0.8 g, 3 mmol) (represented by formula I-1-c), 1-bromo-4-nitrobenzene (0.606 g, 3 mmol) (I-4-a), 1 mol/L sodium carbonate aqueous solution (6 mL) and Pd(PPh.sub.3).sub.2Cl.sub.2 (106 mg, 0.15 mmol) were added to 30 mL of 1,4-dioxane, and the reaction flask was ventilated three times with a nitrogen balloon, and the mixture was stirred at 95° C. overnight. The reaction mixture was filtered and concentrated, and the aqueous phase was extracted with ethyl acetate (2×30 mL), the combined organic phase was washed with saturated saline, dried over anhydrous sodium sulfate and concentrated to obtain a crude product, which was purified by column (ethyl acetate:petroleum ether=0-30%) to obtain 0.73 g of 8-(4-nitrophenyl)-1,4-dioxaspiro[4.5]dec-7-ene (I-19-a) as a brown solid, the yield was 90%. .sup.1H NMR (400 MHz, CDCl3) δ 8.24-8.14 (m, 2H), 7.60-7.50 (m, 2H), 6.21 (td, J=4.0, 2.0 Hz, 1H), 4.06 (s, 4H), 2.71 (ddd, J=6.5, 4.2, 1.7 Hz, 2H), 2.59-2.49 (m, 2H), 1.97 (t, J=6.5 Hz, 2H). LC-MS: m/z: (M+H).sup.+=262.3.

[0715] Step 2:

[0716] 8-(4-Nitrophenyl)-1,4-dioxaspiro[4.5]dec-7-ene (I-19-a) and 10% palladium carbon (100 mg) were added to 50 mL of dichloromethane, the reaction flask was ventilated three times with a hydrogen balloon, and the reaction mixture was stirred at room temperature for 4 hours in a hydrogen atmosphere. The reaction mixture was filtered and evaporated to dryness to obtain 560 mg of 4-(1,4-dioxaspiro[4.5]decan-8-yl)aniline (I-19-b) as a brown solid, which was directly used in the next step, the yield was 96%. LC-MS: m/z: (M+H).sup.+=234.3.

[0717] Step 3:

[0718] m-Chloroperoxybenzoic acid (55 mg, 0.246 mmol) was added to a solution of 2-allyl-1-(6-(2-hydroxypropan-2-yl)pyridin-2-yl)-6-(methylthio)-1,2-dihydro-3H-pyrazolo[3,4-d]pyrimidin-3-one (72 mg, 0.2 mmol) (I-1-h) in 15 mL of toluene, and the obtained mixture was stirred at room temperature for 1 hour. The above reaction mixture was concentrated, and then 4-(1,4-dioxaspiro[4.5]decan-8-yl)aniline (I-19-b), 0.15 mL of trifluoroacetic acid and 3 mL of dimethyl sulfoxide were added thereto, and the mixture was stirred at 60° C. overnight. 10 ML of saturated sodium carbonate aqueous solution and 25 mL of water were added to the above reaction mixture, and the mixture was extracted three times with dichloromethane (3×20 mL); then the organic phase was combined, washed with 10 mL of water and 10 mL of saturated sodium chloride solution, respectively, dried over anhydrous sodium sulfate, and concentrated to obtain a crude product; the crude product was separated by thin layer chromatography plate {7M ammonia methanol: (dichloromethane:ethyl acetate=5:1)=1:12} to obtain 60 mg of 6-((4-(1,4-dioxaspiro[4.5]decan-8-yl)phenyl)amino)-2-allyl-1-(6-(2-hydroxypropan-2-yl)pyridin-2-yl)-1,2-dihydro-3H-pyrazolo[3,4-d]pyrimidin-3-one (represented by I-19-c) as a white solid, the yield was 54%. LC-MS: m/z: (M+H).sup.+=543.3.

[0719] Step 4:

[0720] 6-((4-(1,4-Dioxaspiro[4.5]decan-8-yl)phenyl)amino)-2-allyl-1-(6-(2-hydroxypropan-2-yl)pyridin-2-yl)-1,2-dihydro-3H-pyrazolo[3,4-d]pyrimidin-3-one (represented by I-19-c) was added to a mixed solution consisting of 3 mL of tetrahydrofuran and 3 mL of 2 mol/L hydrochloric acid, and the mixture was stirred at room temperature overnight. The pH of the reaction mixture was adjusted to about 10 with sodium bicarbonate, extracted with dichloromethane (2×20 mL), and the crude product was concentrated after the organic phase was dried over anhydrous sodium sulfate. The obtained crude product was separated by thin layer chromatography plate with methanol:(dichloromethane:ethyl acetate=9:3)=1:12 to obtain 50 mg of 2-allyl-1-(6-(2-hydroxypropan-2-yl)pyridin-2-yl)-6-((4-(4-oxocyclohexyl)phenyl)amino)-1,2-dihydro-3H-pyrazolo[3,4-d]pyrimidin-3-one (I-19-d) as a white solid, the yield was 90%. LC-MS: m/z: (M+H).sup.+=499.3.

[0721] Step 5:

[0722] 2-Allyl-1-(6-(2-hydroxypropan-2-yl)pyridin-2-yl)-6-((4-(4-oxocyclohexyl)phenyl)amino)-1,2-dihydro-3H-pyrazolo[3,4-d]pyrimidin-3-one (50 mg, 0.1 mmol) (I-19-d) and ammonium acetate (77 mg, 1 mmol) were added to 10 mL of methanol, the mixture was stirred at room temperature for 10 min, then sodium cyanoborohydride (30 mg, 0.5 mmol) was added thereto, and the mixture was stirred overnight at room temperature. After the reaction mixture was concentrated, 20 mL of dichloromethane was added thereto, and the mixture was washed with 10 mL of 1 mol/L sodium carbonate solution and 5 mL of water sequentially. The organic phase was dried over anhydrous sodium sulfate, and the obtained crude product was concentrated and directly used in the next step. 40 Mg of white solid (I-19-e), the yield was 80%. LC-MS: m/z: (M+H).sup.+=500.3.

[0723] Step 6:

[0724] 2-Allyl-6-((4-(4-aminocyclohexyl)phenyl)amino)-1-(6-(2-hydroxypropan-2-yl)pyridin-2-yl)-1,2-dihydro-3H-pyrazolo[3,4-d]pyrimidin-3-one (35 mg, 0.07 mmol) (I-19-e) and N,N-diisopropylethylamine (0.02 mL) were added to 10 mL of dichloromethane, then methanesulfonyl chloride (9 mg, 0.078 mmol) was added thereto, and the mixture was stirred overnight at room temperature. The reaction mixture was concentrated and then prepared by high performance liquid phase to obtain 9 mg of N-(4-(4-((2-allyl-1-(6-(2-hydroxypropan-2-yl)pyridin-2-yl)-3-oxo-2,3-dihydro-1H-pyrazolo[3,4-d]pyrimidin-6-yl)amino)phenyl)cyclohexyl)methanesulfonamide (I-19) as a white solid, the yield was 22%. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.88 (s, 1H), 7.91 (t, J=7.9 Hz, 1H), 7.77 (d, J=7.9 Hz, 1H), 7.56 (d, J=8.5 Hz, 2H), 7.40 (d, J=7.4 Hz, 1H), 7.19 (d, J=8.5 Hz, 2H), 5.78-5.66 (m, 1H), 5.07 (dd, J=10.2, 1.0 Hz, 1H), 4.96 (dd, J=17.1, 1.2 Hz, 1H), 4.77 (d, J=6.2 Hz, 2H), 4.42 (d, J=7.6 Hz, 1H), 3.49-3.35 (m, 1H), 3.04 (s, 3H), 2.57-2.46 (m, 1H), 2.29-2.17 (m, 2H), 2.05-1.96 (m, 8H), 1.56-1.65 (m, 2H), 1.41-1.50 (m, 2H). LC-MS: m/z: (M+H).sup.+=578.3.

Embodiment 20

[0725] ##STR00177##

[0726] 2-Allyl-6-((4-(4-aminocyclohexyl)phenyl)amino)-1-(6-(2-hydroxypropan-2-yl)pyridin-2-yl)-1,2-dihydro-3H-pyrazolo[3,4-d]pyrimidin-3-one (120 mg, 0.24 mmol) (compound represented by I-19-c), 1H-pyrazole-carboximidamide hydrochloride (45 mg, 0.31 mmol) and N,N-diisopropylethylamine (0.2 mL) were added to 5 mL of N,N-dimethylformamide, the mixture was stirred at 65° C. overnight. The reaction mixture was concentrated and separated by thin layer chromatography plate (7M ammonia methanol:dichloromethane=1:8) to obtain 30 mg of white solid (compound represented by I-20), the yield was 23%. LC-MS: m/z: (M+H).sup.+=542. .sup.1H NMR (400 MHz, MeOD) δ 8.84 (s, 1H), 8.02 (m, 1H), 7.80 (m, 1H), 7.72-7.58 (m, 3H), 7.25 (m, 2H), 5.73 (ddt, J=16.5, 10.3, 6.1 Hz, 1H), 5.05 (dd, J=10.2, 1.0 Hz, 1H), 4.95 (d, 1H), 4.83 (d, J=6.1 Hz, 2H), 3.54-3.42 (m, 1H), 2.59 (m, 1H), 2.14 (m, 1H), 1.98 (m, 2H), 1.83 (m, 1H), 1.68 (m, 2H), 1.60 (s, 6H), 1.50 (m, 2H).

Embodiment 23

[0727] ##STR00178##

[0728] Potassium tert-butoxide (2 equiv., 0.2006 mmol) was dissolved in dry dimethyl sulfoxide (1 mL, 100 mass %), and then a solution of tosylmethyl isocyanide (1.5 equiv., 0.1504 mmol) in dry dimethyl sulfoxide (1 mL) was added thereto at room temperature. Compound (I-19-d) (50 mg, 0.1003 mmol) was dissolved in dry methanol (0.5 mL), the solution was added to the above reaction mixture, and then the reaction was stirred at room temperature for 12 hours. The reaction was quenched with water, and extracted with ethyl acetate (2×20 mL), the the organic phase was washed with saline (1×20 mL), dried over Na.sub.2SO.sub.4, filtered and concentrated to obtain a crude product. The crude product was refined by normal phase silica gel column (elution conditions: dichloromethane/methanol system, methanol concentration from 0% to 10%, 12 column volumes) to obtain compound (I-23): (15 mg, 0.02943 mmol), the yield was 29.35%, yellow solid. .sup.1H NMR (400 MHz, DMSO) δ 10.28 (s, 1H), 8.88 (d, J=1.8 Hz, 1H), 8.09-7.97 (m, 1H), 7.75 (d, J=8.4 Hz, 1H), 7.66 (dd, J=20.6, 8.5 Hz, 3H), 7.19 (dd, J=11.1, 8.7 Hz, 2H), 5.74-5.61 (m, 1H), 5.00 (d, J=10.2 Hz, 1H), 4.82 (d, J=17.1 Hz, 1H), 4.69 (d, J=5.5 Hz, 2H), 3.23 (s, 1H), 2.74 (t, J=12.1 Hz, 1H), 2.53 (s, 1H), 2.12 (d, J=10.1 Hz, 1H), 1.98 (d, J=13.2 Hz, 1H), 1.82 (d, J=13.2 Hz, 2H), 1.77-1.57 (m, 3H), 1.49 (d, J=18.2 Hz, 6H). LC-MS: m/z: (M+H).sup.+=510.2.

Embodiment 31

[0729] ##STR00179## ##STR00180##

[0730] Step 1:

[0731] 3-(4-Bromophenyl)cyclobutanone (I-31-a) (4.40 mmol) was dissolved in dichloromethane (10 mL); triethylamine (8.9 mmol), dimethylamine hydrochloride (8.9 mmol) and sodium triacetoxyborohydride (8.9 mmol) were added to the reaction mixture, and the reaction mixture was stirred at room temperature for 16 hours. The pH value of the reaction mixture was adjusted to 9 with potassium carbonate aqueous solution, the mixture was extracted with dichloromethane, the organic phase was washed with saturated saline, dried over anhydrous sodium sulfate, filtered, and the filtrate was evaporated to dryness to obtain 1.1 g of the crude target compound 3-(4-bromophenyl)-N,N-dimethylcyclobutylamine (represented by I-31-b) as a colorless oil, the yield was 97%. LC-MS: m/z: (M+H).sup.+=255.4.

[0732] Step 2:

[0733] 3-(4-Bromophenyl)-N,N-dimethylcyclobutylamine (I-31-b) (4.30 mmol) was dissolved in toluene (20 mL); and diphenylmethylamine (I-31-c) (4.8 mmol), sodium tert-butoxide (6.9 mmol), 1,1′-binaphthyl-2,2′-bis(diphenylphosphine) (0.43 mmol) and tris(dibenzylideneacetone)dipalladium (0.13 mmol) were added to the reaction mixture, then the reaction was heated to 90° C. and stirred for 16 hours under the protection of nitrogen. The reaction mixture was cooled to room temperature, and concentrated to obtain a crude product, and the crude product was purified by column chromatography (dichloromethane/methanol=100/0-95/5) to obtain 1.5 g of target compound 3-(4-((diphenylmethylene)amino)phenyl)-N,N-dimethylcyclobutanamine (I-31-d) as a colorless oil, the yield was 98%. LC-MS: m/z: (M+H).sup.+=355.3.

[0734] Step 3:

[0735] 4-(3-Dimethylamino)cyclobutyl)aniline (I-31-d) (4.2 mmol) was dissolved in methanol (20 mL), sodium acetate (13.0 mmol) and hydroxylamine hydrochloride (8.5 mmol) were added to the reaction mixture, and the reaction mixture was stirred at 50° C. for 16 hours. The reaction mixture was evaporated to dryness to obtain a crude product, and the crude product was purified by column chromatography (dichloromethane/methanol=100/0-95/5) to obtain 0.75 g of the target compound 4-(3-dimethylamino)cyclobutyl) aniline (I-31-e), the yield was 93%. LC-MS: m/z: (M+H).sup.+=191.3.

[0736] Step 4:

[0737] 2-Allyl-1-(7-hydroxy-7-methyl-6,7-dihydro-5H-cyclopenta[b]pyridin-2-yl)-6-(methylthio)-1,2-dihydro-3H-pyrazolo[3,4-d]pyrimidin-3-one (I-1-h) (0.65 mmol) was dissolved in toluene (20 mL), and 3-chloroperoxybenzoic acid (0.62 mmol) was added thereto, and the reaction mixture was stirred for 0.5 hours at room temperature. 4-(3-Dimethylamino)cyclobutyl)aniline (I-31-e)(0.67 mmol) was added to the reaction mixture, and the reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was evaporated to dryness to obtain a crude product, the crude product was slurried with ethyl acetate and dichloromethane to obtain 92 mg of target compound 2-allyl-6-((4-(3-(dimethylamino)cyclobutyl)phenyl)amino)-1-(6-(2-hydroxypropan-2-yl)pyridin-2-yl)-1,2-dihydro-3H-pyrazolo[3,4-d]pyrimidin-3-one (I-31) as a white solid, the yield was 32.9%. .sup.1H NMR (400 MHz, DMSO) δ 10.27 (s, 1H), 8.89 (s, 1H), 8.12 (s, 1H), 7.74 (dd, J=22.6, 8.3 Hz, 3H), 7.64 (d, J=7.3 Hz, 1H), 7.37 (d, J=8.5 Hz, 2H), 5.76-5.61 (m, 1H), 5.34 (s, 1H), 5.01 (dd, J=10.3, 1.2 Hz, 1H), 4.84 (d, J=17.1 Hz, 1H), 4.70 (d, J=5.7 Hz, 2H), 3.62 (s, 1H), 3.12 (s, 1H), 2.71-2.58 (m, 8H), 2.38 (d, J=9.2 Hz, 2H), 1.47 (s, 6H), 1.32-1.24 (m, 1H). LC-MS: m/z: (M+H).sup.+=500.3.

Embodiment 32

[0738] ##STR00181##

[0739] Compound (I-19-d) (80 mg, 0.1604 mmol, 100 mass %) was dissolved in ethanol (4 mL, 100 mass %), then water (2 mL, 100 mass %) and hydroxylamine hydrochloride (3 equiv., 0.4813 mmol, 100 mass %) were added at room temperature, and the reaction was stirred at 70° C. for 12 hours. The reaction was quenched with aq. NaHCO.sub.3 and extracted with ethyl acetate (2×20 mL), the organic phase was washed with saline (1×20 mL), dried over Na.sub.2SO.sub.4, filtered and concentrated to obtain a crude product. The crude product was washed with 2 mL of methanol and filtered to obtain compound (I-32) (60 mg, 0.1137 mmol), the yield was 70.88%, white solid. .sup.1H NMR (400 MHz, DMSO) δ 10.26 (s, 1H), 8.88 (s, 1H), 8.07 (t, J=7.8 Hz, 1H), 7.76 (d, J=8.0 Hz, 1H), 7.65 (dd, J=14.5, 7.9 Hz, 2H), 7.22 (d, J=8.5 Hz, 2H), 5.74-5.60 (m, 1H), 5.35 (s, 1H), 5.00 (d, J=10.3 Hz, 1H), 4.83 (d, J=17.1 Hz, 1H), 4.69 (d, J=5.6 Hz, 2H), 3.74 (s, 3H), 3.24-3.15 (m, 1H), 2.77 (t, J=12.0 Hz, 1H), 2.37 (d, J=14.0 Hz, 1H), 2.25 (td, J=13.4, 4.6 Hz, 1H), 1.99-1.84 (m, 3H), 1.67-1.50 (m, 2H), 1.49 (d, J=14.0 Hz, 6H). LC-MS: m/z: (M+H).sup.+=528.

Embodiment 33

[0740] ##STR00182##

[0741] Step 1:

[0742] Compound (I-15-c) (400 mg, 1.077 mmol) was dissolved in toluene (20 mL), then m-CPBA (1.2 equiv., 1.292 mmol, 77 mass %) was added thereto at room temperature, and the reaction was stirred for 2 hours at room temperature. Compound (I-33-a) (1.2 equiv., 1.292 mmol) and DIPEA (2 equiv., 2.154 mmol) were added to the above reaction mixture sequentially, and the reaction was continued with stirring at room temperature for 12 hours. The reaction was quenched with water, and extracted with ethyl acetate (2×20 mL), the the organic phase was washed with saline (1×20 mL), dried over Na.sub.2SO.sub.4, filtered and concentrated to obtain a crude product. The crude product was refined by normal phase silica gel column (elution conditions: ethyl acetate/dichloromethane system, ethyl acetate concentration from 0% to 10%, 24 column volumes) to obtain compound (I-33-b): (120 mg, 0.2341 mmol), the yield was 21.74%, yellow solid. .sup.1H NMR (400 MHz, DMSO) δ 8.91 (d, J=2.4 Hz, 1H), 8.11 (t, J=7.9 Hz, 1H), 7.89 (d, J=8.3 Hz, 1H), 7.68 (d, J=8.2 Hz, 2H), 7.57 (d, J=7.7 Hz, 1H), 7.28 (d, J=8.6 Hz, 2H), 5.72 (ddd, J=23.0, 10.3, 5.9 Hz, 1H), 5.02 (dd, J=10.3, 1.3 Hz, 1H), 4.95-4.89 (m, 2H), 4.87 (d, J=1.4 Hz, 1H), 4.75 (d, J=5.8 Hz, 1H), 4.70 (t, J=6.2 Hz, 2H), 3.04 (t, J=11.9 Hz, 1H), 2.67-2.53 (m, 2H), 2.30 (t, J=15.0 Hz, 2H), 2.08 (d, J=10.0 Hz, 2H), 1.96-1.81 (m, 2H).

[0743] Step 2:

[0744] Compound (I-33-b) (100 mg, 0.1951 mmol) was dissolved in methanol (3 mL); and DIPEA (5 equiv., 0.9754 mmol) was added thereto, and the reaction was stirred for 5 min at room temperature. Then, Na(OAc).sub.3BH (3 equiv., 0.5853 mmol) was added, and the reaction was continued with stirring at room temperature for 12 hours. The reaction was quenched with aq. NaHCO.sub.3, and extracted with ethyl acetate (2×20 mL), the the organic phase was washed with saline (1×20 mL), dried over Na.sub.2SO.sub.4, filtered and concentrated to obtain a crude product. The crude product was refined by normal phase silica gel column (elution conditions: dichloromethane/methanol (1% ammonia methanol) system, methanol concentration from 0% to 10%, 12 column volumes) to obtain compound (I-33): (80 mg, 0.15 mmol), the yield was 77.3%, white solid. .sup.1H NMR (400 MHz, MeOD) δ 8.86 (s, 0H), 8.11-8.01 (m, 1H), 7.94 (d, J=7.9 Hz, 2H), 7.67 (d, J=7.6 Hz, 2H), 7.62 (d, J=8.6 Hz, 2H), 7.28 (d, J=8.5 Hz, 2H), 5.83-5.74 (m, 1H), 5.09 (dd, J=7.9, 4.4 Hz, 3H), 4.98 (dd, J=17.1, 1.3 Hz, 2H), 4.85 (d, J=6.7 Hz, 2H), 2.87 (s, 1H), 2.64 (s, 1H), 2.47 (s, 3H), 1.97-1.67 (m, 8H). LC-MS: m/z: (M+H).sup.+=529.2.

Embodiment 34

[0745] ##STR00183##

[0746] Compound (I-33) (40 mg, 0.07582 mmol), cyclopropylacetic acid (1.1 eq., 73 mg) were dissolved in dichloromethane (2 mL), then DIPEA (2 equiv., 0.1516 mmol) and HATU (1 equiv., 0.07582 mmol) were added sequentially, and the reaction was stirred for 6 hours at room temperature. The reaction was quenched with water, and extracted with dichloromethane (2×20 mL), the the organic phase was washed with saline (1×20 mL), dried over Na.sub.2SO.sub.4, filtered and concentrated to obtain a crude product. The crude product was refined by normal phase silica gel column (elution conditions: dichloromethane/methanol system, methanol concentration from 0% to 10%, 12 column volumes) to obtain compound (I-34): (10 mg, 0.01679 mmol), the yield was 22.14%, yellow solid. .sup.1H NMR (400 MHz, MeOD) δ 8.87 (d, J=6.6 Hz, 1H), 8.06 (t, J=7.9 Hz, 1H), 7.95 (d, J=7.9 Hz, 1H), 7.68 (dd, J=7.8, 5.4 Hz, 2H), 7.61 (d, J=8.6 Hz, 1H), 7.41 (d, J=8.4 Hz, 1H), 7.24 (t, J=8.7 Hz, 1H), 5.84-5.72 (m, 1H), 5.09 (d, J=6.2 Hz, 2H), 5.07 (d, J=1.3 Hz, 1H), 5.02-4.94 (m, 2H), 4.90 (s, 2H), 4.84 (d, J=6.7 Hz, 2H), 3.15 (d, J=2.6 Hz, 1H), 3.08 (s, 1H), 2.95 (s, 1H), 2.71 (s, 1H), 2.43 (s, 1H), 1.93-2.03 (m, 3H), 1.76 (s, 2H), 1.51 (s, 1H), 1.31 (d, J=4.3 Hz, 3H), 0.89 (dd, J=20.1, 9.0 Hz, 4H). LC-MS: m/z: (M+H).sup.+=596.2.

Embodiment 35

[0747] ##STR00184##

[0748] Step 1:

[0749] Compound (I-35-a) (100 mg, 0.3444 mmol) was dissolved in tetrahydrofuran (5 mL), and TEA (5 equiv., 1.722 mmol) and compound (I-35-b) (2 equiv., 0.6887 mmol) were added, and the reaction was stirred for 8 hours at room temperature. The reaction was quenched with water, and extracted with ethyl acetate (2×20 mL), the the organic phase was washed with saline (1×20 mL), dried over Na.sub.2SO.sub.4, filtered and concentrated to obtain a crude product. The crude product was refined by normal phase silica gel column (elution conditions: petroleum ether/ethyl acetate system, ethyl acetate concentration from 10% to 60%, 12 column volumes) to obtain compound (I-35-c): (100 mg, 0.2532 mmol), the yield was 73.54%, white solid. LC-MS: m/z: (M+H-tBu).sup.+=339.1.

[0750] Step 2:

[0751] Compound (I-35-c) (200 mg, 0.5065 mmol) was dissolved in tetrahydrofuran (5 mL), then sodium hydride (2 equiv., 1.013 mmol, 60 mass %) was added thereto, and the reaction was stirred for 2 hours at 50° C. The reaction was quenched with water, and extracted with ethyl acetate (2×20 mL), the the organic phase was washed with saline (1×20 mL), dried over Na.sub.2SO.sub.4, filtered and concentrated to obtain compound (I-35-d): (180 mg, 0.502 mmol), the yield was 99.14%, white solid. .sup.1H NMR (400 MHz, MeOD) δ7.31 (dt, J=11.6, 8.5 Hz, 3H), 7.15 (d, J=8.5 Hz, 1H), 4.07-3.92 (m, 1H), 3.47 (dt, J=29.5, 7.2 Hz, 2H), 2.39 (dt, J=16.3, 8.1 Hz, 2H), 2.22 (d, J=10.1 Hz, 1H), 2.03 (s, 4H), 1.84-1.57 (m, 6H), 1.53 (d, J=2.8 Hz, 9H). LC-MS: m/z: (M+H).sup.+=359.1.

[0752] Step 3:

[0753] Compound (I-35-d) (180 mg, 0.669 mmol) was dissolved in dichloromethane (4 mL), then trifluoroacetic acid (1 mL) was added thereto, and the reaction was stirred for 12 hours at room temperature. After the reaction mixture was concentrated, aq. NaHCO.sub.3 was added thereto, and the mixture was extracted with ethyl acetate (2×20 mL); the organic phase was washed with saline (1×20 mL), dried over Na.sub.2SO.sub.4, filtered and concentrated to obtain compound (I-35-e): (120 mg, 0.464 mmol), the yield was 100%, yellow solid. LC-MS: m/z: (M+H).sup.+=259.1.

[0754] Step 4:

[0755] Compound (I-15-c) (100 mg, 0.2693 mmol) was dissolved in toluene (2 mL), then m-CPBA (1.2 equiv., 0.3231 mmol, 77 mass %) was added thereto at room temperature, and the reaction was stirred for 2 hours at room temperature. Compound (I-35-e) (1.2 equiv., 0.3231 mmol) and DIPEA (2 equiv., 0.5385 mmol) were added to the above reaction mixture at room temperature sequentially, and the reaction was continued with stirring at room temperature for 12 hours. The reaction was quenched with water, and extracted with ethyl acetate (2×20 mL), the the organic phase was washed with saline (1×20 mL), dried over Na.sub.2SO.sub.4, filtered and concentrated to obtain a crude product. The crude product was refined by normal phase silica gel column (elution conditions: dichloromethane/tetrahydrofuran system, tetrahydrofuran concentration from 0% to 30%, 12 column volumes) to obtain compound (I-35): (40 mg, 0.06876 mmol), the yield was 25.54%, white solid. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.87-8.79 (m, 1H), 8.14-8.07 (m, 1H), 8.04-7.96 (m, 1H), 7.89-7.80 (m, 1H), 7.61-7.50 (m, 2H), 7.38-7.32 (m, 1H), 7.25-7.19 (m, 1H), 7.01 (t, J=3.4 Hz, 1H), 5.72 (ddd, J=16.6, 11.1, 8.6 Hz, 1H), 5.17-5.09 (m, 2H), 5.04-4.98 (m, 1H), 4.98-4.92 (m, 1H), 4.87-4.77 (m, 2H), 4.73-4.64 (m, 2H), 4.20-4.06 (m, 1H), 3.47-3.38 (m, 1H), 3.38-3.29 (m, 1H), 3.05-2.98 (m, 1H), 2.49-2.35 (m, 2H), 2.27-2.17 (m, 1H), 2.07-1.86 (m, 4H), 1.75-1.60 (m, 3H). LC-MS: m/z: (M+H).sup.+=582.2.

Embodiment 36

[0756] ##STR00185## ##STR00186##

[0757] 2-Allyl-1-(6-(3-hydroxyoxetan-3-yl)pyridin-2-yl)-6-(methylthio)-1,2-dihydro-3H-pyrazolo[3,4-d]pyrimidin-3-one (represented by formula 1-15-c) (200 mg, 0.538 mmol) was dissolved in 5 mL of toluene, and 3-chloroperoxybenzoic acid (140 mg, 0.69 mmol) was added thereto, and the reaction mixture was stirred at 20° C. for 2 hours. The reaction mixture was concentrated to dryness under reduced pressure. The obtained solid was dissolved in 5 mL of DMSO, and trifluoroacetic acid (20 mg, 0.2 mmol) and 4-(4-(azetidin-1-yl)cyclohexyl)aniline (represented by formula I-36-a) (140 mg, 0.64 mmol) were added, and the reaction mixture was stirred at 65° C. for 16 hours. The reaction was quenched with water and then extracted with dichloromethane (30 mL*3), the organic layer was dried over anhydrous sodium sulfate, concentrated and purified by column chromatography (methanol/dichloromethane/ethyl acetate=0.5:10:4 to 1:10:4) to obtain a yellow solid (I-36-2) (22 mg, 7.4%) and a yellow solid (I-36-1) (64 mg, 21.4%). Compound I-36-1: HPLC retention time (RT)=7.14 min (HPLC conditions: mobile phase A was water (containing HCOOH 0.1%), mobile phase B was acetonitrile; gradient elution: 5% mobile phase B.fwdarw.95% mobile phase B), .sup.1H NMR (400 MHz, CDCl.sub.3) δ8.88 (d, J=2.6 Hz, 1H), 8.09 (dd, J=15.0, 7.8 Hz, 1H), 7.99-7.83 (m, 2H), 7.54 (t, J=9.5 Hz, 2H), 7.39 (d, J=8.7 Hz, 1H), 7.21 (d, J=8.5 Hz, 1H), 5.74 (dq, J=10.5, 5.9 Hz, 1H), 5.12 (t, J=8.8 Hz, 3H), 4.99 (d, J=17.1 Hz, 1H), 4.80 (d, J=6.3 Hz, 2H), 4.67 (d, J=6.0 Hz, 2H), 3.39-3.24 (m, 4H), 2.60-2.34 (m, 3H), 2.14 (dt, J=14.0, 6.8 Hz, 3H), 1.96 (d, J=10.8 Hz, 4H), 1.55-1.37 (m, 2H), 1.27-1.12 (m, 2H); LC-MS: m/z: (M+H).sup.+=554.1. Compound I-36-2: HPLC retention time (RT)=7.15 min (HPLC conditions: mobile phase A was water (containing HCOOH 0.1%), mobile phase B was acetonitrile; gradient elution: 5% mobile phase B.fwdarw.95% mobile phase B), .sup.1H NMR (400 MHz, MeOD) δ8.86 (s, 1H), 8.02 (dt, J=24.0, 7.9 Hz, 3H), 7.64 (dd, J=27.1, 8.1 Hz, 3H), 7.27 (t, J=8.6 Hz, 2H), 7.01-6.91 (m, 3H), 6.72-6.64 (m, 3H), 5.79 (ddd, J=16.3, 11.2, 6.1 Hz, 1H), 5.10-5.05 (m, 2H), 4.85 (d, J=6.8 Hz, 2H), 2.57 (d, J=10.7 Hz, 1H), 2.48-2.28 (m, 3H), 2.23-2.06 (m, 3H), 1.98-1.71 (m, 6H), 1.58 (dd, J=23.2, 12.9 Hz, 3H), 1.44 (ddd, J=16.1, 13.2, 3.5 Hz, 2H), 1.19-1.00 (m, 2H); LC-MS: m/z: (M+H).sup.+=554.1.

Embodiment 37

[0758] ##STR00187##

[0759] Step 1:

[0760] Compound (I-35-a) (150 mg, 0.5165 mmol) was dissolved in tetrahydrofuran (6 mL), and DIPEA (5 equiv., 2.583 mmol) and compound (I-35-a) (3 equiv., 1.550 mmol) were added thereto, and the reaction was stirred for 12 hours at room temperature. The reaction was quenched with water, and extracted with ethyl acetate (2×20 mL), the the organic phase was washed with saline (1×20 mL), dried over Na.sub.2SO.sub.4, filtered and concentrated to obtain a crude product. The crude product was refined by normal phase silica gel column (elution conditions: petroleum ether/ethyl acetate system, ethyl acetate concentration from 0% to 40%, 12 column volumes) to obtain compound (I-37-b): (120 mg, 0.3023 mmol), the yield was 58.53%, white solid. .sup.1H NMR (400 MHz, MeOD) δ 7.38-7.27 (m, 2H), 7.24-7.18 (m, 1H), 7.18-7.09 (m, 1H), 4.38-4.23 (m, 2H), 3.83-3.67 (m, 2H), 2.63 (td, J=14.1, 6.0 Hz, 1H), 2.52-2.37 (m, 1H), 2.31 (s, 1H), 2.25-2.13 (m, 1H), 2.00-1.84 (m, 3H), 1.82-1.63 (m, 3H), 1.53 (s, 9H).

[0761] Step 2:

[0762] Compound (I-37-b) (120 mg, 0.30 mmol) was dissolved in tetrahydrofuran (5 mL), then sodium hydride (2 equiv., 0.607 mmol, 60 mass %) was added thereto, and the reaction was stirred for 2 hours at 50° C. The reaction was quenched with water, and extracted with ethyl acetate (2×20 mL), the the organic phase was washed with saline (1×20 mL), dried over Na.sub.2SO.sub.4, filtered and concentrated to obtain compound (I-37-c): (80 mg, 0.22 mmol), the yield was 73.4%, white solid. .sup.1H NMR (400 MHz, MeOD) δ7.31 (dt, J=18.7, 8.6 Hz, 3H), 7.15 (d, J=8.5 Hz, 1H), 4.42-4.26 (m, 2H), 3.66 (ddd, J=16.1, 12.2, 5.9 Hz, 2H), 2.50 (s, 1H), 2.15 (dd, J=17.3, 6.4 Hz, 2H), 1.99-1.79 (m, 4H), 1.77-1.61 (m, 3H), 1.53 (d, J=1.7 Hz, 9H). LC-MS: m/z: (M+H).sup.+=305.1.

[0763] Step 3:

[0764] Compound (I-37-c) (80 mg, 0.22 mmol) was dissolved in dichloromethane (2 mL), then trifluoroacetic acid (1 mL) was added thereto, and the reaction was stirred for 12 hours at room temperature. The reaction mixture was concentrated, then aq. NaHCO.sub.3 was added thereto, and the mixture was extracted with ethyl acetate (2×20 mL), the the organic phase was washed with saline (1×20 mL), dried over Na.sub.2SO.sub.4, filtered and concentrated to obtain a crude product. The crude product was refined by normal phase silica gel column (elution conditions: petroleum ether/ethyl acetate system, ethyl acetate concentration from 0% to 50%, 12 column volumes) to obtain compound (I-37-d): (60 mg, 0.2305 mmol), the yield was 100%, yellow solid. .sup.1H NMR (400 MHz, MeOD) δ 7.11 (d, J=8.1 Hz, 1H), 7.00 (d, J=8.3 Hz, 1H), 6.78-6.66 (m, 2H), 4.40-4.29 (m, 2H), 3.70-3.57 (m, 4H), 2.10 (d, J=17.5 Hz, 1H), 1.97-1.81 (m, 4H), 1.72-1.57 (m, 3H). LC-MS: m/z: (M+H).sup.+=261.1.

[0765] Step 4:

[0766] Compound (I-15-c) (60 mg, 0.1616 mmol) was dissolved in toluene (2 mL), then m-CPBA (1.2 equiv., 0.1939 mmol, 77 mass %) was added thereto at room temperature, and the reaction was stirred for 2 hours at room temperature. Compound (I-37-d) (1.4 equiv., 0.2262 mmol) and DIPEA (2 equiv., 0.3231 mmol) were added to the above reaction mixture at room temperature sequentially, and the reaction was continued with stirring at room temperature for 12 hours. The reaction was quenched with water, and extracted with ethyl acetate (2×20 mL), the the organic phase was washed with saline (1×20 mL), dried over Na.sub.2SO.sub.4, filtered and concentrated to obtain a crude product. The crude product was refined by normal phase silica gel column (elution conditions: dichloromethane/tetrahydrofuran system, tetrahydrofuran concentration from 0% to 50%, 12 column volumes) to obtain compound (I-37): (15 mg, 0.02570 mmol), the yield was 15.91%, yellow solid. .sup.1H NMR (400 MHz, CDCl.sub.3) δ8.77 (s, 1H), 8.16-8.07 (m, 1H), 8.03 (d, J=7.6 Hz, 1H), 7.83-7.75 (m, 1H), 7.56 (dd, J=12.6, 6.1 Hz, 2H), 7.33 (d, J=8.5 Hz, 1H), 7.21 (d, J=8.5 Hz, 1H), 5.72 (dd, J=17.0, 10.3 Hz, 1H), 5.13 (dd, J=9.1, 6.1 Hz, 2H), 4.96 (d, J=17.0 Hz, 2H), 4.81 (d, J=7.2 Hz, 2H), 4.69 (d, J=6.2 Hz, 2H), 4.41-4.28 (m, 2H), 3.86 (s, 1H), 3.77 (t, J=6.6 Hz, 1H), 3.63-3.50 (m, 2H), 2.98 (m, 1H), 2.15 (m, 1H), 1.97 (dd, J=18.9, 9.6 Hz, 2H), 1.78 (d, J=5.0 Hz, 2H), 1.65 (d, J=8.7 Hz, 2H). LC-MS: m/z: (M+H).sup.+=584.1.

Embodiment 38

[0767] ##STR00188##

[0768] Step 1:

[0769] Compound (I-33-a) (150 mg, 0.79260 mmol) was dissolved in dichloromethane (2 mL), and then (Boc).sub.2O (1.2 equiv., 0.95112 mmol) and DIPEA (2 equiv., 1.5852 mmol) were added thereto, and the reaction was stirred at room temperature for 12 hours. The reaction was quenched with water and extracted with dichloromethane (2×20 mL), the organic phase was washed with saline (1×20 mL), dried over Na.sub.2SO.sub.4, filtered and concentrated to obtain compound (I-38-a): (250 mg, 0.8639 mmol), the yield was 100.0%, yellow solid. .sup.1H NMR (400 MHz, DMSO) δ 9.25 (s, 1H), 7.37 (d, J=8.4 Hz, 2H), 7.17 (d, J=8.6 Hz, 2H), 2.98 (ddd, J=12.0, 8.7, 3.3 Hz, 1H), 2.65-2.52 (m, 2H), 2.25 (dd, J=12.5, 2.0 Hz, 2H), 2.11-1.97 (m, 2H), 1.83 (ddd, J=25.9, 13.2, 4.0 Hz, 2H), 1.47 (s, 9H).

[0770] Step 2:

[0771] Potassium tert-butoxide (3 equiv., 1.866 mmol) was dissolved in dry tetrahydrofuran (1 mL), and then a solution of tosylmethyl isocyanide (1.5 equiv., 0.933 mmol) in dry tetrahydrofuran (1 mL) was added thereto at room temperature. Compound (I-38-a) (180 mg, 0.6220 mmol) was dissolved in dry methanol (0.5 mL), the solution was added to the above reaction mixture, and then the reaction was stirred at room temperature for 12 hours. The reaction was quenched with water, and extracted with ethyl acetate (2×20 mL), the the organic phase was washed with saline (1×20 mL), dried over Na.sub.2SO.sub.4, filtered and concentrated to obtain a crude product. The crude product was refined by normal phase silica gel column (elution conditions: dichloromethane/methanol system, methanol concentration from 0% to 10%, 12 column volumes) to obtain compound (I-38-b): (60 mg, 0.1997 mmol), the yield was 32.11%, yellow solid. LC-MS: m/z: (M+H).sup.+=244.7.

[0772] Step 3:

[0773] Compound (I-38-b) (50 mg, 0.16 mmol) was dissolved in dichloromethane (2 mL), then trifluoroacetic acid (1 mL) was added thereto, and the reaction was stirred for 12 hours at room temperature. After the reaction mixture was concentrated, aq. NaHCO.sub.3 was added thereto, and the mixture was extracted with ethyl acetate (2×20 mL); the organic phase was washed with saline (1×20 mL), dried over Na.sub.2SO.sub.4, filtered and concentrated to obtain compound (I-38-c): (50 mg, 0.159 mmol), the yield was 96%, yellow solid. LC-MS: m/z: (M+H).sup.+=201.1.

[0774] Step 4:

[0775] Compound (I-15-c) (50 mg, 0.1346 mmol) was dissolved in toluene (2 mL), then m-CPBA (1.2 equiv., 0.1616 mmol, 77 mass %) was added thereto at room temperature, and the reaction was stirred for 2 hours at room temperature. Compound (I-38-c) (50 mg, 0.1346 mmol) and DIPEA (2 equiv., 0.2693 mmol) were added to the above reaction mixture at room temperature sequentially, and the reaction was continued with stirring at room temperature for 12 hours. The reaction was quenched with water, and extracted with ethyl acetate (2×20 mL), the the organic phase was washed with saline (1×20 mL), dried over Na.sub.2SO.sub.4, filtered and concentrated to obtain a crude product. The crude product was refined by normal phase silica gel column (elution conditions: dichloromethane/tetrahydrofuran system, tetrahydrofuran concentration from 0% to 30%, 12 column volumes) to obtain compound (I-38): (10 mg, 0.01910 mmol), the yield was 14.19%, white solid. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.69 (s, 1H), 8.18 (d, J=8.0 Hz, 1H), 8.10 (dd, J=17.9, 7.6 Hz, 1H), 7.81-7.72 (m, 1H), 7.63-7.49 (m, 2H), 7.25 (d, J=8.4 Hz, 1H), 7.19 (d, J=8.3 Hz, 1H), 5.70 (d, J=6.8 Hz, 1H), 5.15 (d, J=10.1 Hz, 1H), 5.14-5.07 (m, 1H), 4.95 (d, J=16.6 Hz, 1H), 4.83 (t, J=6.7 Hz, 2H), 4.71 (s, 2H), 2.54 (dd, J=24.9, 12.6 Hz, 2H), 2.30 (d, J=11.2 Hz, 1H), 2.18 (d, J=13.5 Hz, 1H), 2.02 (d, J=12.9 Hz, 1H), 1.96-1.80 (m, 2H), 1.78 (d, J=16.1 Hz, 1H), 1.49 (dd, J=26.4, 11.2 Hz, 2H). LC-MS: m/z: (M+H).sup.+=524.1.

Embodiment 40

[0776] ##STR00189##

[0777] Compound (I-39) (70 mg, 0.12 mmol) was dissolved in a mixture of ethanol (2 mL), tetrahydrofuran (2 mL) and water (2 mL), then lithium hydroxide monohydrate (15 mg, 0.36 mmol) was added thereto, and the reaction mixture was concentrated after stirring at room temperature for 16 hours; the reaction mixture was purified by thin layer chromatography (dichloromethane: ammonia methanol (7 M): ethyl acetate=7:1:1) to obtain a white solid (I-40) (40 mg, 60%). .sup.1H NMR (400 MHz, Methanol-d.sub.4) δ 8.84 (s, 1H), 8.05 (t, J=7.9 Hz, 1H), 7.92 (d, J=8.1 Hz, 1H), 7.66 (dd, J=7.6, 0.9 Hz, 1H), 7.63-7.53 (m, 2H), 7.22-7.14 (m, 2H), 5.84-5.74 (m, 1H), 5.10-5.07 (m, 2H), 5.06 (q, J=1.3 Hz, 1H), 4.98 (dq, J=17.0, 1.4 Hz, 1H), 4.89 (dt, J=6.1, 1.4 Hz, 2H), 2.71 (d, J=6.9 Hz, 1H), 2.59 (s, 1H), 2.24 (dd, J=16.4, 7.8 Hz, 2H), 2.04 (d, J=8.5 Hz, 1H), 1.73 (td, J=10.9, 6.8 Hz, 6H). LC-MS: m/z: [M+1]+=543.0.

Embodiment 41

[0778] ##STR00190##

[0779] Compound (I-41-1) and compound (I-41-2) can be synthesized by the same method as in embodiment 1 using 5-bromo-2-nitropyridine as raw material. Compound 1-41-1: HPLC retention time (RT)=6.17 min (HPLC conditions: mobile phase A was water (containing HCOOH 0.1%), mobile phase B was acetonitrile; gradient elution: 5% mobile phase B.fwdarw.95% mobile phase B), .sup.1H NMR (400 MHz, Chloroform-d) δ 9.00 (s, 1H), 8.30 (d, J=8.6 Hz, 1H), 8.22 (d, J=2.4 Hz, 1H), 7.96 (t, J=7.9 Hz, 1H), 7.73 (dd, J=8.1, 0.8 Hz, 1H), 7.55 (dd, J=8.7, 2.4 Hz, 1H), 7.44 (dd, J=7.7, 0.8 Hz, 1H), 5.77-5.66 (m, 1H), 5.12-5.05 (m, 1H), 4.97 (dq, J=17.0, 1.4 Hz, 1H), 4.76 (dt, J=6.3, 1.3 Hz, 2H), 2.70 (s, 1H), 2.56 (s, 6H), 2.23 (q, J=9.5 Hz, 4H), 2.11-2.01 (m, 4H), 1.58 (t, J=10.3 Hz, 6H). LC-MS: m/z: [M+1].sup.+=529.1. Compound 1-41-2: HPLC retention time (RT)=6.28 min (HPLC conditions: mobile phase A was water (containing HCOOH 0.1%), mobile phase B was acetonitrile; gradient elution: 5% mobile phase B.fwdarw.95% mobile phase B), .sup.1H NMR (400 MHz, Chloroform-d) δ8.99 (s, 1H), 8.54 (s, 1H), 8.32 (d, J=8.7 Hz, 1H), 8.26 (d, J=2.4 Hz, 1H), 8.10 (t, J=7.7 Hz, 1H), 7.92 (s, 1H), 7.78 (dd, J=8.1, 0.8 Hz, 1H), 7.47-7.41 (m, 1H), 5.79-5.71 (m, 1H), 5.08 (dq, J=10.1, 1.2 Hz, 1H), 4.97 (dq, J=17.0, 1.3 Hz, 1H), 4.77 (dt, J=6.2, 1.4 Hz, 2H), 3.99 (s, 1H), 2.75 (d, J=11.0 Hz, 1H), 2.52 (s, 6H), 2.32-2.18 (m, 1H), 2.09 (d, J=14.4 Hz, 4H), 1.31 (d, J=22.8 Hz, 4H). LC-MS: m/z: [M+1].sup.+=529.1.

[0780] With reference to the above embodiments, the compounds shown in Table 1 were prepared, and their structural characteristics were as follows:

TABLE-US-00001 TABLE 1 List of compounds Compound Structure Characterization data Method I-2 [00191] .sup.1H NMR (400 MHz, MeOD) δ 8.85 (s, 1H), 8.00 (t, J = 7.9 Hz, 1H), 7.80 (d, J = 8.1 Hz, 1H), 7.68 (d, J = 7.7 Hz, 1H), 7.62 (d, J = 8.6 Hz, 2H), 7.28 (d, J = 8.6 Hz, 2H), 5.78-5.68 (m, 1H), 5.06 (d, J = 10.3 Hz, 1H), 4.95 (s, 1H), 4.82 (s, 2H), 3.82-3.76 (m, 1H), 2.81 (s, 1H), 2.71 (s, 3H), 2.49 (s, 1H), 2.08 (d, J = 10.9 Hz, 3H), 1.94 (d, J = 15.0 Hz, 3H), 1.72 (s, 4H), 1.59 (d, J = 7.0 Hz, 6H). LC-MS: m/z: (M + H).sup.+ = 570.3. I-1 I-8 [00192] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.86 (s, 1H), 7.93-7.85 (m, 1H), 7.78 (d, J = 7.8 Hz, 1H), 7.52 (d, J = 8.5 Hz, 2H), 7.39 (dd, J = 7.6, 0.7 Hz, 1H), 7.19 (d, J = 8.5 Hz, 2H), 5.71 (ddt, J = 16.4, 10.2, 6.2 Hz, 1H), 5.05 (dd, J = 10.2, 1.1 Hz, 1H), 4.94 (dd, J = 17.1, 1.3 Hz, 1H), 4.77 (d, J = 6.2 Hz, 2H), 4.11 (d, J = 8.9 Hz, 1H), 3.24 (t, J = 7.0 Hz, 4H), 2.52-2.43 (m, 1H), 2.14-2.00 (m, 3H), 1.92 (d, J = 11.2 Hz, 4H), 1.60 (s, 6H), 1.45 (dt, J = 14.9, 7.5 Hz, 2H) 1.23-1.08 (m, 2H). LC-MS: m/z: (M + H).sup.+ = 540.4. I-1 See embodiment 8 for details I-8-1 [00193] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.86 (s, 1H), 7.93-7.85 (m, 1H), 7.78 (d, J = 7.8 Hz, 1H), 7.52 (d, J = 8.5 Hz, 2H), 7.39 (dd, J = 7.6, 0.7 Hz, 1H), 7.19 (d, J = 8.5 Hz, 2H), 5.71 (ddt, J = 16.4, 10.2, 6.2 Hz, 1H), 5.05 (dd, J = 10.2, 1.1 Hz, 1H), 4.94 (dd, J = 17.1, 1.3 Hz, 1H), 4.77 (d, J = 6.2 Hz, 2H), 4.11 (d, J = 8.9 Hz, 1H), 3.24 (t, J = 7.0 Hz, 4H), 2.52-2.43 (m, 1H), 2.14-2.00 (m, 3H), 1.92 (d, J = 11.2 Hz, 4H), 1.60 (s, 6H), 1.45 (dt, J = 14.9, 7.5 Hz, 2H) 1.23-1.08 (m, 2H). LC-MS: m/z: (M + H).sup.+ = 540.4. After testing, its retention time was unique: HPLC retention time (RT) = 10.78 min (HPLC conditions: mobile phase A was water (containing HCOOH 0.1%), mobile phase B was acetonitrile; gradient elution: 5% mobile phase B.fwdarw.50% mobile phase B). Therefore, its cyclohexyl moiety was cis or trans. This can be further corroborated by together embodiment 8-2. I-1 See embodiment 8-1 for details I-8-2 [00194] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.87 (s, 1H), 7.92 (d, J = 7.8 Hz, 1H), 7.80 (d, J = 8.0 Hz, 1H), 7.52 (d, J = 8.4 Hz, 2H), 7.39 (d, J = 7.6 Hz, 1H), 7.29-7.25 (m, 2H), 5.82-5.63 (m, 1H), 5.12-4.91 (m, 2H), 4.78 (d, J = 6.2 Hz, 2H), 4.01 (s, 1H), 3.17 (s, 4H), 2.53 (s, 1H), 2.33 (s, 1H), 2.06 (d, J = 4.4 Hz, 2H), 1.89 (d, J = 11.6 Hz, 2H), 1.75 (d, J = 14.1 Hz, 2H), 1.59 (d, J = 17.2 Hz, 8H), 1.46 (t, J = 13.1 Hz, 2H). LC-MS: 540.0 [M + H].sup.+. HPLC retention time (RT) = 10.997 min (HPLC conditions: mobile phase A was water (containing HCOOH 0.1%), mobile phase B was acetonitrile; gradient elution: 5% mobile phase B.fwdarw.50% mobile phase B). See embodiment 8-2 or embodiment 8-3 I-17 [00195] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.84 (d, J = 3.7 Hz, 1H), 7.94 (dd, J = 14.8, 6.9 Hz, 1H), 7.76 (d, J = 7.9 Hz, 1H), 7.58-7.50 (m, 2H), 7.42 (dd, J = 7.5, 4.1 Hz, 1H), 7.22 (dd, J = 15.8, 8.5 Hz, 2H), 5.71 (dd, J = 11.5, 5.4 Hz, 2H), 5.07 (d, J = 10.2 Hz, 1H), 4.95 (d, J = 17.1 Hz, 1H), 4.77 (d, J = 6.1 Hz, 2H), 2.82-2.72 (m, 1H), 2.60 (s, 1H), 2.12-2.01 (m, 3H), 1.92 (d, J = 12.5 Hz, 1H), 1.81-1.67 (m, 3H), 1.62 (s, 6H), 1.54-1.43 (m, 1H), 0.93-0.78 (m, 3H), 0.52 (s, 2H). LC-MS: m/z: (M + H).sup.+ = 568.4. I-7 I-39 [00196] .sup.1H NMR (400 MHz, Methanol-d.sub.4) δ 8.85 (d, J = 1.1 Hz, 1H), 8.05 (td, J = 7.9, 4.8 Hz, 1H), 7.96-7.86 (m, 1H), 7.67 (d, J = 7.6 Hz, 1H), 7.59 (ddd, J = 9.2, 4.6, 2.3 Hz, 2H), 7.25-7.19 (m, 1H), 7.19-7.11 (m, 1H), 5.78 (ddt, J = 16.5, 10.1, 6.1 Hz, 1H), 5.12-5.07 (m, 2H), 5.06 (t, J = 1.3 Hz, 1H), 4.98 (dd, J = 17.0, 1.4 Hz, 1H), 4.90 (d, J = 1.4 Hz, 2H), 4.25-4.19 (m, 1H), 4.14 (dd, J = 14.1, 7.1 Hz, 1H), 2.34-2.12 (m, 2H), 2.07 (dd, J = 17.0, 4.1 Hz, 1H), 1.99-1.82 (m, 1H), 1.74-1.65 (m, 2H), 1.65-1.53 (m, 2H) 1.31 (d, J = 4.2 Hz, 3H) 1.29-1.25 (m, 2H). LC-MS: m/z: [M + H].sup.+ = 571.1. I-4

Effect Embodiment 1

[0781] I. Inhibitory Effect of Compound on WEE1 Kinase In Vitro

[0782] Test Method:

[0783] The tested compounds were screened on WEE1 kinase with ATP concentration of K.sub.m by ELISA. Compounds were screened on WEE1 kinase to evaluate the kinase inhibitory activity of the tested compounds. In the detection process, the initial concentration of the tested compounds was all selected as 100 nM, and each compound was selected with 6 gradient dilution concentrations, the gradient dilution ratio was 4-fold, and two replicate wells were detected for each concentration, MK1775 was used as the standard control.

[0784] WEE1, purchased from CarnaBiosciences, Inc., Item No. 05-177; dimethyl sulfoxide, purchased from Sigma-Aldrich, Item No. D8418; ATP, purchased from Sigma-Aldrich, Item No. A7699; DTT solution, purchased from Sigma-Aldrich, Item No. 43816; protein tyrosine kinase (PTK) substrate (poly-Glu-Tyr), purchased from Sigma-Aldrich, Item No. P4476; P-Tyr (PY99), purchased from Santa Cruz, Item No. sc-7020; Anti-mouse IgG HRP-linked Antibody, purchased from Santa Cruz, Item No. 7076S; TMB liquid Substrate System, purchased from Sigma-Aldrich, Item No. T0440; Costar Stripwell Microplate No Lid 1×8 Flat Bottom, Certified High Binding, purchased from Sigma-Aldrich, Item No. 42592; 96-well compound plate, purchased from Thermo Scientific, Item No. 267245.

[0785] Test Steps:

[0786] 1. Coating substrate: 1) An appropriate volume of substrate storage solution protein tyrosine kinase (PTK) substrate (poly-Glu-Tyr) was taken, diluted 10 times with PBS, and the concentration was diluted from 250 mg/mL to 25 mg/mL. The mixture was added to a high adsorption 96-well plate at 125 μL per well. The plate was placed in an incubator at 37° C. for overnight coating. 2) After 24 hours, the 96-well plate was taken out, the liquid in the 96-well plate was poured out, cleaned with washing buffer for 3 times, and the incubator at 37° C. was inverted and dried for 2 hours.

[0787] 2. Compound preparation and transfer: 1) compound dilution: 10 mM of the test compound storage solution was taken, the compound in 96-well compound plate was diluted with DMSO in multiple steps to obtain the initial concentration of 100× compound as the first concentration, and then DMSO was used for 4-fold gradient dilution, for a total of 6 concentrations; after that, 2 μL of the gradient dilution solution was added to 48 μL of 1× reaction buffer respectively to prepare 4× compound; 2) 4× compounds were transferred: 10 μL of 4× compounds from the 96-well compound plate configured in the previous step were transferred into the dried high adsorption 96-well plate; 10 μL of the following liquids were added to the compound-free control wells and ATP-control wells: 2 μL of DMSO was added to 48 μL of 1× reaction buffer.

[0788] 3. Enzyme reaction stage: 1) WEE1 kinase and ATP were prepared into 2× enzyme solution and 4×ATP solution respectively with 1× reaction buffer. In this screening, the final concentration of WEE1 kinase was: 0.15 ng/μL and the final concentration of ATP was: 12 M; 2) 20 μL of enzyme solution of 2 was added to the high adsorption 96-well plate; 3) 10 μL of 4×ATP solution was added to the high adsorption 96-well plate and 10 μL of 1× reaction buffer was added to the ATP-control group; 4) the plate was placed in HERAEUS Multifuge X1R centrifuge at 2000 rpm for 20 s and then placed at room temperature and reacted for 60 min.

[0789] 4. Reaction termination stage: 1) the reaction mixture in the plate was poured out, 200 μL of washing buffer was added to each well, and washed for 5 times; the primary antibody P-Tyr (PY99) (dilution ratio 1:2000) was added, 100 μL per well, at room temperature for 30 min. 2) The primary antibody in the plate was poured out, 200 μL of washing buffer was added to each well, and washed for 5 times; the second antibody Anti-mouse IgG HRP-linked Antibody (dilution ratio 1:2000) was added, 100 μL per well, at room temperature for 30 min. 3) The secondary antibody in the plate was poured out, washed 5 times with washing buffer, and TMB was added, 100 μL per well, and colored for 10-30 min, depending on the color depth. The reaction was terminated with 1N sulfuric acid before reading.

[0790] 5. Detection and data processing: 1) The light absorption at 450 nM was read on ThermoScientific MultiScan GO, and the background was read at 650 nM at the same time. 2) Graphpad Prism 5.0 was used to fit Log(inhibitor) vs. response-Variable slope (four parameters) curves to the data, and the corresponding IC.sub.50 (half maximal inhibitory concentration) was calculated.

[0791] II. The Data of the Test Result.

[0792] The structure of the control samples used in the tests was shown in Table 2.

TABLE-US-00002 TABLE 2 Structure of control sample Control sample number Chemical structure Control 1 (AZD1775/MK1775) [00197] Control 2 (WO 2019/096322 Al Patent Compound) [00198]

[0793] The test results were detailed in Table 3.

TABLE-US-00003 TABLE 3 Test results of WEEE 1 enzyme inhibitory activity and cell inhibitory activity Compound WEE1 Compound WEE1 number IC.sub.50, nM number IC.sub.50, nM Control 1 2.57 Control 2 1.98 I-1-1 1.90 I-1-2 2.08 I-2 2.57 I-3-1 0.35 I-3-2 0.66 I-5 7.15 I-6 6.76 I-7 6.53 I-8 1.52 I-8-1 1.52 I-8-2 3.52 I-15-1 1.52 I-15-2 1.68 I-17 4.05 I-19 3.89 I-20 3.45 I-23 0.71 I-31 2.05 I-32 7.39 I-33 4.22 I-34 3.30 I-36-2 2.92 I-37 1.99 I-38 1.68 I-39 2.08 I-40 4.58 I-41-1 2.11 I-41-2 2.74

[0794] Conclusion: As shown in Table 3, the compounds of the present disclosure have a good inhibitory effect on Wee1 kinase.

Effect Embodiment 2 Bioavailability Test In Vivo in Mice

[0795] I. Experimental Animals and Test Products

[0796] 1. Experimental Animal

TABLE-US-00004 Species Strain Certificate number Weight (g) Number (pcs) Mice ICR 20180006002806 20 60

[0797] All the above were provided by Shanghai Sino-British SIPPR Lab. Animal Ltd.

[0798] 2. Preparation of Test Products

[0799] 2.1 Preparation of Mother Liquor

[0800] 404.6 μL of DMSO was added to the compound powder of the present disclosure until the compound was completely dissolved, and 50 mg/mL mother liquor was prepared in a clarified state.

[0801] 2.2 Preparation of Administration Solution

[0802] The compound of the present disclosure: 24 μL of mother liquor was accurately measured, diluted to 4 mL according to the ratio of 0.9% normal saline: PEG400=8:2, the preparation concentration was 0.3 mg/mL, the solution was in a clarified state, and it was used as intravenous administration solution. In addition, 80 μL mother liquor was accurately measured, and 0.5% CMC-Na was added to 8 mL to grind it into a uniform suspension with a concentration of 0.5 mg/mL, which was used as intragastric administration solution.

[0803] II. Animal Experiments

[0804] Intravenous group: 24 ICR mice, 20±2 g, were given the intravenous administration solution of the compound of the present disclosure by intravenous injection, with the volume of 10 mL/kg, with the dose of 3 mg/kg, the blood was taken from the fundus venous plexus of mice, 2, 5, 15, 30, 60, 90, 120, 240, 360, 480, 600 and 1440 minutes before and after administration.

[0805] Intragastric group: 24 ICR mice, 20±2 g, were given the intragastric administration solution of the compound of the present disclosure by intragastric injection, with the volume of 20 mL/kg, with the dose of 10 mg/kg, the blood was taken from the fundus venous plexus of mice, 5, 15, 30, 60, 90, 120, 240, 360, 480, 600 and 1440 minutes before and after administration.

[0806] Blood sample was centrifuged at 8000 rpm for 5 min, and the plasma was stored in a centrifuge tube at −20° C. for later use.

[0807] III. Treatment of Plasma Samples

[0808] 1. Preparation of Standard Curve

[0809] The concentration range of standard working solution was 60, 20, 6, 2, 0.6, 0.2, 0.1, 0.04 μg/mL.

[0810] 47.5 μL of blank mouse plasma was taken and 2.5 μL of standard curve working solution was added to prepare samples with a series of concentrations of 3, 1, 0.3, 0.1, 0.03, 0.01, 0.005, 0.002 and 0.001 g/mL; the samples were vortexed evenly, and 300 μL of acetonitrile containing internal standard (Propranolol, 25 ng/mL) was added to precipitate protein, the samples were vortexed for 10 min, 6000 g, 4° C., centrifuged for 10 min, and the supernatant was injected into a 96-well plate.

[0811] 2. Treatment of QC Sample

[0812] The concentration range of QC working solution: Low: 0.06 μg/mL; Middle: 1.6 μg/mL; High: 48 μg/mL.

[0813] 47.5 μL of blank mouse plasma was taken and 2.5 μL of QC working solution was added to prepare samples with a series of concentrations of 2.4, 0.08, 0.003 μg/mL; the samples were vortexed evenly, and 300 μL of acetonitrile containing internal standard (Propranolol, 25 ng/mL) was added to precipitate protein, the samples were vortexed for 10 min, 6000 g, 4° C., centrifuged for 10 min, and the supernatant was injected into a 96-well plate.

[0814] 3. Treatment of Plasma Samples

[0815] 300 μL of acetonitrile containing internal standard (Propranolol, 25 ng/mL) was added to 50 μL of plasma samples to precipitate protein, vortexed for 10 min, 6000 g, 4° C., centrifuged for 10 min; the supernatant before intravenous injection for 1 hour was taken, diluted 10 times with acetonitrile containing internal standard, the rest supernatant was kept undiluted, centrifuged for 10 min again at 6000 g, 4° C., and the supernatant was taken and then injected into a 96-well plate.

[0816] IV. Experimental Results of Bioavailability in Mice

[0817] 1. Test Parameters

[0818] Dose; peak concentration: C.sub.max; peak time: T.sub.max; area under the drug-time curve from AUC.sub.last 0 to time t; half-life: T.sub.1/2; mean retention time: MRT; clearance: Cl; apparent distribution volume: V.sub.z; steady-state distributed volume: V.sub.ss; absolute bioavailability: F.

[0819] 2. Pharmacokinetics Data of Mice

[0820] The pharmacokinetic parameters of the compound in mice after intravenous injection or intragastric administration were shown in Table 4 and Table 5 below.

TABLE-US-00005 TABLE 4 Pharmacokinetic parameters of compounds in mice Control 1 (MK1775) Control 2 I-1-1 I-8 iv po iv po iv po iv po Dose mg/kg 3 10    3    10    3 10    3 10    C.sub.max ng/mL 773.8 ± 53.79 205.2 ± 124.5 646.4 ± 76.85 27.79 ± 4.76 700.8 ± 142.5 245.2 ± 220.3 644.0 ± 132.2 58.08 ± 1.09  T.sub.max h 0.05 ± 0.03 0.33 ± 0.14 0.03  1.67 ± 2.02 0.03 2.50 ± 1.32 0.03 AUC.sub.last (h) * (ng/mL) 273.1 ± 21.34 151.7 ± 62.14 261.52 ± 26.93 80.15 ± 9.62 372.5 ± 24.38 528.6 ± 331.1 317.5 ± 34.41 637.9 ± 302.3 T.sub.1/2 h 0.65 ± 0.03 3.10 ± 0.22  1.37 ± 0.33  2.51 ± 1.85 4.31 ± 1.51 3.10 ± 9.02 1.22 ± 0.10 1.57 ± 0.39 MRT h 0.42 ± 0.02 4.33 ± 0.28  0.86 ± 0.16  3.78 ± 1.56 1.75 ± 0.46 4.33 ± 9.02 1.11 ± 0.08 3.47 ± 1.22 Cl L/kg * h 10.99 ± 0.87  /  11.3 ± 1.20 / 7.74 ± 0.36 / 9.29 ± 0.85 / Vz L/kg 10.31 ± 1.12  /  22.2 ± 3.29 / 48.52 ± 18.38 / 16.33 ± 2.48  / Vss L/kg 4.58 ± 0.44 /  9.69 ± 0.96 / 13.61 ± 3.95  / 10.32 ± 0.86  / F % 16.67  9.19 42.57 60.27

TABLE-US-00006 TABLE 5 Pharmacokinetic parameters of compounds in mice I-8-1 iv po Dose mg/kg 3 10 C.sub.max ng/mL 644.0 ± 132.2 58.08 ± 7.09  T.sub.max h 0.03 1.67 ± 0.29 AUC.sub.last (h)*(ng/mL) 317.5 ± 34.41 637.9 ± 302.3 T.sub.1/2 h 1.22 ± 0.10 1.57 ± 0.39 MRT h 1.11 ± 0.08 3.47 ± 1.22 Cl L/kg*h 9.29 ± 0.85 / Vz L/kg 16.33 ± 2.48  / Vss L/kg 10.32 ± 0.86  / F % 60.27

[0821] Conclusion: The compound of the present disclosure can significantly improve the pharmacokinetics of mice.

Effect Embodiment 3 Bioavailability Test In Vivo in Cynomolgus Monkey

[0822] I. Experimental Animals and Subjects

[0823] Twelve male Non-Naïve cynomolgus monkeys were purchased from GuangxiGuidong Primate Development Experiment Co. LTD.

TABLE-US-00007 Administration Administration Number Dose concentration volume Administration Sample Grouping Subjects Male (mg/kg) (mg/mL) (mL/kg) mode collection 1 I-8-1 3 3 1.5 2 IV Plasma 2 3 20 4 5 PO* Plasma 3 AZD1775 3 3 1.5 2 IV Plasma 4 3 20 4 5 PO* Plasma Note: *indicates the oral fasting, the food was withdrawn from 16:00-17:00 p.m. the day before the administration, and the food was added about 4 hours after the administration in the morning of the administration.

[0824] II. Preparation of Subjects

[0825] The test product was prepared with free alkali concentration, and the purity was not converted.

[0826] III. Preparation of Administration Solution

[0827] I. Preparation of I-8-1:

[0828] 54.31 mg of I-8-1 was accurately weighed, and 1.08 mL of DMSO was added, then the mixture was vortexed for 1 min, sonicated for 15 min, and then diluted to 36 mL according to the ratio of 10% HP-β-cyclodextrin (prepared by normal saline): PEG=8:2, vortexed for 1 min. A colorless clarified administration solution (the pH value was about 7) at a concentration of 1.5 mg/mL was prepared for intravenous administration to Group 1.

[0829] 300.9 mg of I-8-1 was accurately weighed, and 75 mL of 0.5% CMC-Na was added, the mixture was fully ground and stirred for 5 min. A white suspension (the pH value was about 7) at a concentration of 4 mg/mL was prepared for oral administration to Group 2.

[0830] 2. Preparation of AZD1775:

[0831] 54.05 mg of AZD1775 was accurately weighed, and 1.08 mL of DMSO was added, then he mixture was vortexed for 1 min, sonicated for 15 min, and then diluted to 36 mL according to the ratio of 10%-D-cyclodextrin (prepared by normal saline): PEG=8:2, vortexed for 1 min. A yellow clarified administration solution (the pH value was about 7) at a concentration of 1.5 mg/mL was prepared for intravenous administration to Group 3.

[0832] 300.7 mg of AZD1775 was accurately weighed, and 75 mL of 0.5% CMC-Na was added, the mixture was fully ground and stirred for 5 min. A yellow suspension (the pH value was about 7) at a concentration of 4 mg/mL was prepared for oral administration to Group 4.

[0833] IV. Animal Experiments

[0834] 1. Dose and Mode of Administration

[0835] Before administration, all animals were fasted overnight (approximately 12 hours) and fed as required and administered according to the table below.

TABLE-US-00008 Subjects Subjects Solution Administration Weight Dose concentration* volume Dose Route of Grouping Gender Subjects (kg) (mg/kg) (mg/ml) (mL/kg) (mL) administration 1 M I-8-1 2.30 3 1.5 2 4.6 IV 1 M I-8-1 2.30 3 1.5 2 4.6 IV 1 M I-8-1 2.45 3 1.5 2 5.0 IV 2 M I-8-1 2.50 20 4 5 13 PO 2 M I-8-1 2.85 20 4 5 14 PO 2 M I-8-1 2.45 20 4 5 12 PO 3 M AZD1775 2.35 3 1.5 2 4.8 IV 3 M AZD1775 2.55 3 1.5 2 5.2 IV 3 M AZD1775 2.35 3 1.5 2 4.8 IV 4 M AZD1775 2.20 20 4 5 11 PO 4 M AZD1775 2.30 20 4 5 12 PO 4 M AZD1775 2.50 20 4 5 13 PO *Drug concentration was calculated according to free base. **All animals were fasted overnight before administration (withdrawn at 16:00-17:00 pm approximately the day before administration) and fed 4 hours after administration on the morning of the day of administration.

[0836] 2. Collection and Treatment of Plasma Samples

[0837] Intravenous group: before administration (0 h), 0.033 h, 0.083 h, 0.25 h, 0.5 h, 1 h, 1.5 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h after administration.

[0838] Oral group: before administration (0 h), 0.083 h, 0.25 h, 0.5 h, 1.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h after administration.

[0839] Blood samples were collected by puncture through lower limb vein or other suitable blood vessels at 1 mL/time point (3 mL of blood samples were collected from each animal before administration), anticoagulated with heparin sodium, and placed on ice after collection. Plasma was separated at 2200 g/min, 10 min, 2-8° C., plasma samples were stored in a −80° C. refrigerator before being transferred to the client. Plasma samples are stored in dry ice and transferred to the client. The final treatment of the sample will be recorded in the experimental record.

[0840] V. Treatment of Plasma Samples

[0841] I. Preparation of Standard Curve

[0842] The concentration range of standard working solution was 60, 20, 6, 2, 0.6, 0.2, 0.1, 0.04, 0.02 μg/mL.

[0843] 47.5 μL of blank cynomolgus monkey plasma was taken and 2.5 μL of standard curve working solution was added to prepare samples with a series of concentrations of 3, 1, 0.3, 0.1, 0.03, 0.01, 0.005, 0.002 and 0.001 g/mL; the samples were vortexed evenly, and 300 μL of acetonitrile containing internal standard (Propranolol, 25 ng/mL) was added to precipitate protein, the samples were vortexed at 6000 g, centrifuged for 10 min. 80 μL of supernatant was injected into a 96-well plate.

[0844] 2. Treatment of QC Sample

[0845] The concentration range of QC working fluid: Low: 0.06 μg/mL; Middle: 1.6 μg/mL; High: 48 g/mL.

[0846] 47.5 μL of blank cynomolgus monkey plasma was taken and 2.5 μL of standard curve working solution was added to prepare samples with a series of concentrations of 2.4, 0.08 and 0.003 μg/mL; the samples were vortexed evenly, and 300 μL of acetonitrile containing internal standard (Propranolol, 25 ng/mL) was added, the samples were vortexed at 6000 g, centrifuged for 10 min. 80 μL of supernatant was injected into a 96-well plate.

[0847] 3. Treatment of Plasma Samples

[0848] 300 μL of acetonitrile was added to 50 μL of plasma samples containing internal standard (Propranolol, 25 ng/mL) to precipitate protein, vortexed for 10 min, centrifuged at 6000 g for 10 min, after I-8-1&AZD1775 intravenous injection group was diluted 10 times with internal standard acetonitrile (Propranolol, 25 ng/mL) at the time point before 1 hour, the remaining supernatant was not diluted, centrifuged again at 6000 g at 4° C. for 10 min, and the supernatant was taken and injected into a 96 well plate.

[0849] VI. Experimental Results of Bioavailability in Cynomolgus Monkeys

[0850] 1. Test Parameters

[0851] Dose; peak concentration: C.sub.max; peak time: T.sub.max; area under the drug-time curve from AUC.sub.last 0 to time t; half-life: T.sub.1/2; mean retention time: MRT; clearance: Cl; apparent distribution volume: V.sub.z; steady-state distributed volume: V.sub.ss; absolute bioavailability: F.

[0852] 2. Pharmacokinetics Data

[0853] The pharmacokinetic parameters of the compound in cynomolgus monkeys after intravenous injection or intragastric administration were shown in Table 6 below.

TABLE-US-00009 TABLE 6 Pharmacokinetic parameters of compounds in cynomolgus monkeys Parameters AZD1775-iv AZD1775-po I-8-1-iv I-8-1-po Dose mg/kg 3 20 3 20 C.sub.max ng/mL  1202 ± 134.2 1627. ± 243.7 838.4 ± 190.0 720.8 ± 260.4 T.sub.max h 2.69 ± 4.60 2.00 0.03 4.50 ± 2.60 AUC.sub.last (h)*(ng/mL) 4494 ± 1719  8155 ± 818.2 957.6 ± 126.3 6548 ± 3043 AUC.sub.extra (h)*(ng/mL) 47.62 ± 58.18 8.46 ± 1.91 16.11 ± 9.34  187.03 ± 166.00 AUCtot (h)*(ng/mL) 4542 ± 1777  8163 ± 819.7 973.8 ± 131.4 6735 ± 3201 thalf h 2.78 ± 0.26 2.03 ± 1.22 2.05 ± 1.24 3.71 ± 0.72 MRT h 6.53 ± 2.51 3.58 ± 0.07 3.17 ± 0.82 7.91 ± 2.00 Clearance L/h/kg 0.72 ± 0.23 / 3.12 ± 0.43 / Vz L/kg 2.84 ± 0.76 / 8.78 ± 4.22 / Vss L/kg 4.33 ± 0.74 / 9.67 ± 1.32 / BA % 27.22 102.56

[0854] Conclusion: The compound of the present disclosure can significantly improve the pharmacokinetics of cynomolgus monkeys.

[0855] Although the specific embodiments of the present disclosure have been described above, those skilled in the art should understand that these are only examples, various changes or modifications can be made to these embodiments without departing from the principle and essence of the present invention. Therefore, the protection scope of the present disclosure is defined by the appended claims.