N-SULFONAMIDE NITROGEN-CONTAINING FUSION HETEROCYCLIC COMPOUND AND ITS APPLICATIONS

Claims

1. A nitrogen-containing compound of formula I, an isotopically labeled compound based on it, a solvate thereof, a pharmaceutically acceptable salt thereof, or a solvate of a pharmaceutically acceptable salt thereof, , Where each of X 1 , X 2 and X 3 independently selected from CH and N; each of R 1 , R 2 , R 3 , R 4 and R 5 independently selected from hydrogen and deuterium; R 6 is -(CH2) n R 7 ; at the same time n is 0, 1, 2, or 3; R 7 selected from C1-C6 alkyl, deuterated C1-C6 alkyl, C1-C6 haloalkyl and C3-C6 cycloalkyl.

2. A compound of formula I, an isotopically labeled compound based on it, a solvate thereof, a pharmaceutically acceptable salt thereof, or a solvate of a pharmaceutically acceptable salt thereof according to claim 1, wherein the compound of formula I is represented by formula Ia .

3. A compound of formula I, an isotopically labeled compound based on it, a solvate thereof, a pharmaceutically acceptable salt thereof, or a solvate of a pharmaceutically acceptable salt thereof according to claim 1, wherein X 1 represents N; X 2 represents CH or N; X 3 represents CH; or X 1 represents N; X 2 and X 3 represent CH.

4. A compound of formula I, an isotopically labeled compound based on it, a solvate thereof, a pharmaceutically acceptable salt thereof, or a solvate of a pharmaceutically acceptable salt thereof according to claim 1, wherein R 6 is -(CH2) n R 7 ; at the same time n is 0 or 1; R 7 selected from C1-C3 alkyl, deuterated C1-C3 alkyl, C1-C3 haloalkyl and C3-C6 cycloalkyl.

5. A compound of formula I, an isotopically labeled compound based on it, a solvate thereof, a pharmaceutically acceptable salt thereof, or a solvate of a pharmaceutically acceptable salt thereof according to claim 1, wherein R 6 is -(CH2) n R 7 ; at the same time n is 0 or 1; R 7 selected from -CH3, -CD3, -CF3 and cyclopropyl.

6. A compound of formula I, an isotopically labeled compound based on it, a solvate thereof, a pharmaceutically acceptable salt thereof, or a solvate of a pharmaceutically acceptable salt thereof according to claim 1, wherein R 1 , R 2 and R 3 represent deuterium; R 4 and R 5 represent hydrogen; or R 1 , R 2 and R 3 represent hydrogen; R 4 and R 5 represent deuterium.

7. A compound of formula I, an isotopically labeled compound based on it, a solvate thereof, a pharmaceutically acceptable salt thereof, or a solvate of a pharmaceutically acceptable salt thereof according to claim 1, wherein formula I is formula Ib or Ic, , ; in formulas Ib and Ic, where represents or ; each of R 1 , R 2 , R 3 , R 4 and R 5 independently selected from hydrogen and deuterium; R 6 is -(CH2) n R 7 ; at the same time n is 0 or 1; R 7 selected from C1-C6 alkyl, C1-C6 haloalkyl and C3-C6 cycloalkyl.

8. A compound of formula I, an isotopically labeled compound based on it, a solvate thereof, a pharmaceutically acceptable salt thereof, or a solvate of a pharmaceutically acceptable salt thereof according to claim 7, wherein in formulas Ib and Ic selected from -OCH3 and -OCD3; R4 and R 5 selected from hydrogen; R 6 is -(CH2) n R 7 ; where n is 0 or 1; R 7 selected from -CH3, -CD3, -CF3 and cyclopropyl.

9. A compound of formula I, an isotopically labeled compound based on it, a solvate thereof, a pharmaceutically acceptable salt thereof, or a solvate of a pharmaceutically acceptable salt thereof according to claim 1, wherein the compound of formula I is selected from the following compounds: , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , And , their enantiomer or a mixture of two of them in any ratio.

10. A pharmaceutical composition comprising a compound of formula I, an isotopically labeled compound based on it, a solvate thereof, a pharmaceutically acceptable salt thereof, or a solvate of a pharmaceutically acceptable salt thereof according to claim 1, and a pharmaceutical excipient.

11. A method for facilitating the binding of mutant p53 characterized by Y220C to DNA, wherein the method comprises administering to a patient a therapeutically effective amount of a compound of formula I, an isotopically labeled compound thereof, a solvate thereof, a pharmaceutically acceptable salt thereof, or a solvate of a pharmaceutically acceptable salt thereof according to claim 1.

12. A method for facilitating the binding of mutant p53 characterized by Y220C to DNA, wherein the method comprises administering to a patient a therapeutically effective amount of the pharmaceutical composition of claim 10.

13. A method for treating gastric cancer, wherein the method comprises administering to the patient a therapeutically effective amount of a compound of formula I, an isotopically labeled compound thereof, a solvate thereof, a pharmaceutically acceptable salt thereof, or a solvate of a pharmaceutically acceptable salt thereof according to claim 1.

14. Compound of formula a-11 or a-32 , , where X is halogen; R 8 is a protecting group for the amino group; each of X 1 , X 2 and X 3 independently selected from CH and N; each of R 1 , R 2 and R 3 independently selected from hydrogen or deuterium; R 6 is -(CH2) n R 7 ; at the same time n is 0, 1, 2, or 3; R 7 selected from C1-C6 alkyl, deuterated C1-C6 alkyl, C1-C6 haloalkyl and C3-C6 cycloalkyl.

15. A compound of formula a-11 or a-32 according to claim 14, wherein the compound of formula a-11 or a-32 is one of the following compounds , , , or .