1,2-dihydro-3H-pyrazolo[3,4-d]pyrimidin-3-one derivative as Wee1 inhibitor
The present invention provides a 1,2-dihydro-3H-pyrazolo[3,4-d]pyrimidin-3-one compound having an inhibitory effect on Wee1, and includes an application of the compound in treating various types of tumors.
1. The compound represented by formula (I) or a pharmaceutically acceptable salt thereof,
wherein,
T 1 is N or CH;
R 1 is selected from H, halogen, OH, NH 2 , or selected from the group consisting of C 1-3 alkyl and
C 1-3 heteroalkyl, each of which is optionally substituted by 1, 2 or 3 R;
R 2 is H, or selected from the group consisting of C 1-3 alkyl, C 1-3 heteroalkyl and 3-6 membered heterocycloalkyl, each of which is optionally substituted by 1, 2 or 3 R;
R 3 is selected from the group consisting of C 3-5 alkenyl and
ring A is selected from the group consisting of phenyl and 5-6 membered heteroaryl, each of which is optionally substituted by 1, 2 or 3 R;
R 5 is selected from halogen, OH, NH 2 , —C(═O)NH 2 , or selected from the group consisting of C 1-6 alkyl, C 1-6 heteroalkyl, C 3-6 cycloalkyl, 3-6 membered heterocycloalkyl, C 3-6 cycloalkyl-O—, 3-6 membered heterocycloalkyl-O— and
each of which is optionally substituted by 1, 2 or 3 R;
R 4 is selected from the group consisting of C 1-6 alkyl, C 3-5 alkenyl, phenyl, and —C 1-3 alkyl -phenyl, each of which is optionally substituted by 1, 2 or 3 R;
R is selected from F, Cl, Br, I, OH, NH 2 , NH(CH 3 ), N(CH 3 ) 2 , Me, Et, CH 2 F, CHF 2 , CF 3 ,
the “hetero” in C 1-3 heteroalkyl, C 1-6 heteroalkyl, 5-6 membered heteroaryl, 3-6 membered heterocycloalkyl is selected from the group consisting of —O—, —S—, —C(═O)—, —C(═O)NH—, —C(═O)O—, —NH— and N;
In any one of the cases above, the number of the heteroatoms or the heteroatom groups is independently selected from 1, 2 or 3.
2. The compound or the pharmaceutically acceptable salt as defined in claim 1 , wherein, R 1 is selected from H, F, Cl, Br, I, OH, NH 2 , or selected from the group consisting of C 1-3 alkyl and C 1-3 alkoxyl, each of which is optionally substituted by 1, 2 or 3 R.
3. The compound or the pharmaceutically acceptable salt as defined in claim 2 , wherein R 1 is selected from the group consisting of H, F, Cl, Br, I, OH, NH 2 , Me and
4. The compound or the pharmaceutically acceptable salt as defined in claim 1 , wherein, R 2 is H, or selected from the group consisting of C 1-3 alkyl, —C(═O)—C 1-3 alkyl, —C(═O)O—C 1-3 alkyl and oxetanyl, each of which is optionally substituted by 1, 2 or 3 R.
5. The compound or the pharmaceutically acceptable salt as defined in claim 4 , wherein, R 2 is selected from the group consisting of H, Me,
6. The compound or the pharmaceutically acceptable salt as defined in claim 1 , wherein, ring A is selected from the group consisting of phenyl, pyridinyl, pyrimidyl, thienyl, thiazolyl, and isothiazolyl, each of which is optionally substituted by 1, 2 or 3 R.
7. The compound or the pharmaceutically acceptable salt as defined in claim 6 , wherein, ring A is selected from the group consisting of
each of which is optionally substituted by 1, 2 or 3 R.
8. The compound or the pharmaceutically acceptable salt as defined in claim 7 , wherein, ring A is selected from the group consisting of
9. The compound or the pharmaceutically acceptable salt as defined in claim 1 , wherein, R 5 is selected from F, Cl, Br, I, OH, NH 2 , —C(═O)NH 2 , or selected from the group consisting of C 1-3 alkyl, C 1-3 alkoxyl, —C(═O)NH—C 1-3 alkyl, C 3-6 cycloalkyl, oxetanyl, 2-pyrrolidinonyl, cyclopropyl-O—, cyclobutyl-O—, oxacyclobutyl-O—, oxacyclopentyl-O—, azocyclobutyl, 2-oxazolidinonyl, 2-imidazolidinonyl and
each of which is optionally substituted by 1, 2 or 3 R.
10. The compound or the pharmaceutically acceptable salt as defined in claim 9 , wherein, R 5 is selected from F, Cl, Br, I, OH, NH 2 , —C(═O)NH 2 , or selected from the group consisting of Me, Et,
each of which is optionally substituted by 1, 2 or 3 R.
11. The compound or the pharmaceutically acceptable salt as defined in claim 10 , wherein, R 5 is selected from the group consisting of F, Cl, Br, I, OH, NH 2 , —C(═O)NH 2 , Me,
12. The compound or the pharmaceutically acceptable salt as defined in claim 8 , wherein, said
is selected from the group consisting of
13. The compound or the pharmaceutically acceptable salt as defined in claim 12 , wherein, R 3 is selected from the group consisting of
14. The compound or the pharmaceutically acceptable salt as defined in claim 1 , wherein, R 4 is selected from the group consisting of C 1-3 alkyl, C 3-5 alkenyl, phenyl, and benzyl, each of which is optionally substituted by 1, 2 or 3 R.
15. The compound or the pharmaceutically acceptable salt as defined in claim 14 , wherein, R 4 is selected from the group consisting of Me,
each of which is optionally substituted by 1, 2 or 3 R.
16. The compound or the pharmaceutically acceptable salt as defined in claim 1 , wherein, the moiety
is selected from the group consisting of
17. The compound or the pharmaceutically acceptable salt defined in claim 1 is selected from:
wherein,
R 1 , R 2 , R 5 , T 1 and ring A are as defined in claim 1 .
18. The compound or the pharmaceutically acceptable salt as defined in claim 17 is selected from the group consisting of
wherein, R 1 , R 2 , R 5 are as defined in claim 17 .
19. The compound or the pharmaceutically acceptable salt thereof shown as below is selected from the group consisting of