Macrocyclic compound serving as Wee1 inhibitor and applications thereof

1. A compound represented by formula (II), an (R)-isomer thereof, an (S)-isomer or a pharmaceutically acceptable salt thereof,

wherein,

is a single bond or a double bond;

R 1 is selected from H and C 1-3 alkyl, wherein the C 1-3 alkyl is optionally substituted by R, and the number of R is 1, 2, or 3;

R 5 is selected from H and C 1-3 alkyl, wherein the C 1-3 alkyl is optionally substituted by R, and the number of R is 1, 2, or 3;

R 6 is selected from R 61 ,

r is 1 or 2;

m is 1 or 2;

D is selected from —N(R 2 )—, N + (O − )(R 2 )—, and —C(R 3 )(R 4 )—;

R 2 is selected from H and C 1-3 alkyl, wherein the C 1-3 alkyl is optionally substituted by R, and the number of R is 1, 2, or 3;

R 3 and R 4 are independently selected from H, F, Cl, Br, I, OH, NH 2 , and C 1-3 alkyl wherein the NH 2 and the C 1-3 alkyl are optionally substituted by R, and the number of R is 1, 2, or 3;

alternatively, R 3 and R 4 together with the carbon atom to which they are attached form a 5-7 membered cycloalkyl or a 5-7 membered heterocycloalkyl, wherein the 5-7 membered cycloalkyl and the 5-7 membered heterocycloalkyl are optionally substituted by R, and the number of R is 1, 2, or 3;

R 61 is selected from H, F, Cl, Br, I, OH, NH 2 , C 1-3 alkoxy, and —O—C 3-6 cycloalkyl, wherein the C 1-3 alkoxy and the —O—C 3-6 cycloalkyl are optionally substituted by R, and the number of R is 1, 2, or 3;

R 7 is selected from H, F, Cl, Br, I, OH, NH 2 , C 1-3 alkyl, C 1-3 alkoxy, and 5-6 membered heterocycloalkyl, wherein the C 1-3 alkyl, C 1-3 alkoxy, and 5-6 membered heterocycloalkyl are optionally substituted by R, and the number of R is 1, 2, or 3;

alternatively, R 6 and R 7 together with the ring atoms to which they are attached form ring A, and the moiety

and

R is independently selected from F, Cl, Br, I, OH, NH 2 , C 1-3 alkyl, C 1-3 alkoxy, and C 1-3 alkylamino, the C 1-3 alkylamino being a C 1-3 alkyl group connected to a part of the molecule via an amino; and

the 5-7 membered heterocycloalkyl contains 1, 2, 3 or 4 heteroatoms or heteroatom groups independently selected from —NH—, —S—, and N.

2. The compound the (R)-isomer thereof, the (S)-isomer thereof, or the pharmaceutically acceptable salt thereof as defined in claim 1 , wherein the R is independently selected from F, Cl, Br, I, OH, NH 2 , CH 3 , Et, —OCH 3 , and

3. The compound, the (R)-isomer thereof, the (S)-isomer thereof, or the pharmaceutically acceptable salt thereof as defined in claim 1 , wherein the R 1 is selected from H, CH 3 , and Et;

or, the R 2 is selected from H, CH 3 , and Et;

or, the R 3 and R 4 are independently selected from H, F, Cl, Br, I, OH, NH 2 , —NH(CH 3 ), —N(CH 3 ) 2 , CH 3 , and Et;

or, the R 5 is selected from H, CH 3 , and Et, wherein the CH 3 and Et are optionally substituted by R, and the number of R is 1, 2, or 3;

or, the R 61 is selected from H, F, Cl, Br, I, OH, NH 2 , —OCH 3 ,

wherein the —OCH 3 ,

are optionally substituted by R, and the number of R is 1, 2, or 3;

or, the R 6 , is selected from R 61 ,

or, the R 7 is selected from H, F, Cl, Br, I, OH, NH 2 , CH 3 , —OCH 3 ,

wherein the CH 3 , —OCH 3 ,

are optionally substituted by R, and the number of R is 1, 2, or 3;

or, the moiety

is selected from

4. The compound, the (R)-isomer thereof, the (S)-isomer thereof, or the pharmaceutically acceptable salt thereof as defined in claim 3 , wherein the R 3 is selected from H, F, Cl, Br, I, OH, NH 2 , —NH(CH 3 ), —NH(CH 3 ) 2 , CH 3 , and Et.

5. The compound, the (R)-isomer thereof, the (S)-isomer thereof, or the pharmaceutically acceptable salt thereof as defined in claim 3 , wherein the R 4 is selected from H, F, Cl, Br, I, OH, CH 3 , and Et.

6. The compound, the (R)-isomer thereof, the (S)-isomer thereof, or the pharmaceutically acceptable salt thereof as defined in claim 3 , wherein the R 5 is selected from H, CH 3 , and —CH 2 OH.

7. The compound, the (R)-isomer thereof, the (S)-isomer thereof, or the pharmaceutically acceptable salt thereof as defined in claim 3 , wherein the R 61 is selected from H, F, Cl, Br, I, OH, NH 2 , —OCH 3 ,

8. The compound, the (R)-isomer thereof, the (S)-isomer thereof, or the pharmaceutically acceptable salt thereof as defined in claim 3 , wherein the R 6 is selected from R 61 ,

9. The compound, the (R)-isomer thereof, the (S)-isomer thereof, or the pharmaceutically acceptable salt thereof as defined in claim 1 , wherein the R 3 and R 4 together with the carbon atom to which they are attached form a 5-7 membered cycloalkyl or 5-7 membered heterocycloalkyl, and the 5-7 membered cycloalkyl or 5-7 membered heterocycloalkyl is optionally substituted by R, and the number of R is 1, 2, or 3;

then the moiety

10. The compound, the (R)-isomer thereof, the (S)-isomer thereof, or the pharmaceutically acceptable salt thereof as defined in claim 1 , wherein the R 6 is selected from H, F, Cl, Br, I, OH, NH 2 , —OCH 3 ,

11. The compound, the (R)-isomer thereof, the (S)-isomer thereof, or the pharmaceutically acceptable salt thereof as defined in claim 3 , wherein the R 7 is selected from H, F, Cl, Br, I, OH, NH 2 , —OCH 3 ,

12. The compound, the (R)-isomer thereof, the (S)-isomer thereof, or the pharmaceutically acceptable salt thereof as defined in claim 1 , which is selected from

wherein,

D is selected from —N(R 2 )—, —N + (Q − )(R 2 )—, and —C(R 3 )(R 4 )—;

r, m, R 1 , R 2 , R 3 , R 4 , R 5 , R 61 , and R 7 are as defined in claim 1 ;

the carbon atom with “*” is a chiral carbon atom and exists in the form of (R) or (S) single enantiomer or enriched in one enantiomer.

13. The compound, the (R)-isomer thereof, the (S)-isomer thereof, or the pharmaceutically acceptable salt thereof as defined in claim 12 , which is selected from

wherein,

D is selected from —N(R 2 )—, —N + (Q − )(R 2 )—, and —C(R 3 )(R 4 )—;

r, R 1 , R 2 , R 3 , and R 4 are as defined in claim 12 ;

the carbon atom with “*” is a chiral carbon atom and exists in the form of (R) or (S) single enantiomer or enriched in one enantiomer.

14. The compound, the (R)-isomer thereof, the (S)-isomer thereof, or the pharmaceutically acceptable salt thereof as defined in claim 13 , which is selected from

wherein R 1 , R 2 , R 3 , and R 4 are as defined in claim 13 ;

the carbon atom with “*” is a chiral carbon atom and exists in the form of (R) or (S) single enantiomer or enriched in one enantiomer.

15. A method for treating tumors in a subject in need thereof, comprising: administering an effective amount of the compound or the pharmaceutically acceptable salt thereof as defined in claim 1 in a subject in need thereof.

16. A compound as shown below, an (R)-isomer thereof, an (S)-isomer thereof, or a pharmaceutically acceptable salt thereof, which is selected from

17. The compound, the (R)-isomer thereof, the (S)-isomer thereof, or the pharmaceutically acceptable salt thereof as defined in claim 16 , which is selected from

18. A method for treating tumors in a subject in need thereof, comprising: administering an effective amount of the compound or the pharmaceutically acceptable salt thereof as defined in claim 16 in a subject in need thereof.

19. The method for treating tumors in a subject in need thereof as defined in claim 15 , wherein the tumors are solid tumors.

20. The method for treating tumors in a subject in need thereof as defined in claim 18 , wherein the tumors are solid tumors.