Granted Patent B2

US 12,473,286 · App. 18/671,458 · Granted Nov 18, 2025

Inventors: Zhongjiang Jia (Kennett Square, PA); Jiacheng Zhou (Newark, DE); Qun Li (Newark, DE)

Assignee: Incyte Corporation

C07D471/14A61P35/00C07B2200/13

Abstract

Claims (19)

1 . A salt which is an acid salt of 3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-(morpholin-4-ylmethyl)-1,3,4,7-tetrahydro-2H-pyrrolo[3′,2′: 5,6]pyrido[4,3-d]pyrimidin-2-one, having the structure:

or a hydrate or solvate thereof, wherein the acid is hydrochloric acid; wherein the salt is crystalline, and wherein the salt has at least one characteristic XRPD peak selected from about 6.8, about 9.2, about 12.9, about 15.6, and about 16.1 degrees 2-theta.

2 . The salt of claim 1 which is a hydrate.

3 . The salt of claim 1 which is a solvate.

4 . A pharmaceutical composition comprising a salt of claim 1 , and a pharmaceutically acceptable carrier or excipient.

5 . A solid oral dosage form comprising the pharmaceutical composition of claim 4 .

6 . A method of inhibiting an FGFR, said method comprising: contacting the FGFR with a salt of claim 1 .

7 . A method of treating FGFR-mediated cancer comprising administering to a patient in need thereof a therapeutically effective amount of a salt of claim 1 .

8 . The method of claim 7 , wherein the cancer is selected from bladder cancer, breast cancer, cervical cancer, cancer of the small intestine, colorectal cancer, endometrial cancer, gastric cancer, head and neck cancer, kidney cancer, liver cancer, lung cancer, ovarian cancer, prostate cancer, testicular cancer, uterine cancer, vulvar cancer, esophageal cancer, gall bladder cancer, pancreatic cancer, thyroid cancer, skin cancer, brain cancer, leukemia, multiple myeloma, chronic lymphocytic lymphoma, adult T cell leukemia, B-cell lymphoma, acute myelogenous leukemia, Hodgkin's or non-Hodgkin's lymphoma, Waldenstrom's Macroglubulinemia, myeloproliferative neoplasms, chronic myelogenic lymphoma, acute lymphoblastic lymphoma, hairy cell lymphoma, Burkett's lymphoma, glioblastoma, melanoma, rhabdosarcoma, lymphosarcoma, and osteosarcoma.

9 . The method of claim 8 wherein the cancer is bladder cancer.

10 . The method of claim 8 wherein the liver cancer is cholangiocellular carcinoma.

11 . The method of claim 8 wherein the myeloproliferative neoplasm is 8p11 myeloproliferative syndrome.

12 . The salt of claim 1 , having at least two characteristic XRPD peaks selected from about 6.8, about 9.2, about 12.9, about 15.6, and about 16.1 degrees 2-theta.

13 . The salt of claim 1 , having at least three characteristic XRPD peaks selected from about 6.8, about 9.2, about 12.9, about 15.6, and about 16.1 degrees 2-theta.

14 . The salt of claim 1 , having an X-ray powder diffraction pattern with characteristic peaks as substantially shown in FIG. 13 .

15 . The salt of claim 1 , which exhibits a DSC thermogram having endothermic peaks at temperatures of about 120° C., about 189° C., and about 274° C.

16 . The salt of claim 1 , which exhibits a DSC thermogram having an endothermic peak at a temperature of about 189° C.

17 . The salt of claim 1 , which exhibits a DSC thermogram having an endothermic peak at a temperature of about 274° C.

18 . The salt of claim 1 , having a DSC thermogram substantially as depicted in FIG. 14 .

Assignments (3)

Continuity (4)

References Cited (400)