Granted Patent B2

US 12,459,917 · App. 17/607,464 · Granted Nov 4, 2025

Inventors: Yanping Zhao (Beijing, CN); Hongjun Wang (Beijing, CN); Zewang Feng (Beijing, CN); Huai Huang (Beijing, CN); Kai Liu (Beijing, CN); Xuelian Liu (Beijing, CN); Jianmei Pang (Beijing, CN); Nana Tian (Beijing, CN); Xichao Chen (Beijing, CN); Shenzhen Fu (Beijing, CN); Jie Meng (Beijing, CN); Liying Zhou (Beijing, CN); Yanan Liu (Beijing, CN)

Assignee: BEIJING TIDE PHARMACEUTICAL CO., LTD.

C07D401/12C07B2200/13

Abstract

Claims (97)

1 . A salt of Compound A,

which is Compound A hydrochloride;

the molar ratio of Compound A to hydrochloric acid is 1:1;

the Compound A hydrochloride is in crystalline form Ia;

the crystalline form Ia has an XRPD pattern comprising characteristic peaks at diffraction angles (20) of 7.8±0.2°, 10.4±0.2°, 15.7±0.2°, 20.0±0.2°, 20.7±0.2°, 22.3±0.2° and 26.0±0.2°.

2 . A salt of Compound A,

which is Compound A hydrochloride;

the molar ratio of Compound A to hydrochloric acid is 1:1;

the Compound A hydrochloride is in crystalline form Ob;

the crystalline form Ib has an XRPD pattern comprising characteristic peaks at diffraction angles (20) of 5.4±0.2°, 11.2±0.2° 13.6±0.2°, and 20.0±0.2°.

3 . A salt of Compound A,

which is Compound A hydrochloride;

the molar ratio of Compound A to hydrochloric acid is 1:2;

the Compound A hydrochloride is in crystalline form II;

the crystalline form II has an XRPD pattern comprising characteristic peaks at diffraction angles (20) of 13.3±0.2°, 14.2±0.2°, 21.9±0.2° and 27.4±0.2°.

4 . A salt of Compound A,

wherein the salt is Compound A citrate;

the molar ratio of Compound A to citric acid is 1:0.5;

the Compound A citrate is in crystalline form III;

the crystalline form III has an XRPD pattern comprising characteristic peaks at diffraction angles (20) of 6.9±0.2°, 10.8±0.2°, 14.6±0.2°, 20.3±0.2° and 22.5±0.2°;

or,

wherein the salt is Compound A sulfate;

the molar ratio of Compound A to sulfuric acid is 1:0.5;

the Compound A sulfate is in crystalline form IV;

the crystalline form IV has an XRPD pattern comprising characteristic peaks at diffraction angles (20) of 8.0±0.2°, 11.2±0.2°, 20.9±0.2°, 21.8±0.2° and 26.3±0.2°;

or,

wherein the salt is Compound A sulfate;

the molar ratio of Compound A to sulfuric acid is 1:1;

the Compound A sulfate is in crystalline form V;

the crystalline form V has an XRPD pattern comprising characteristic peaks at diffraction angles (20) of 7.9±0.2°, 11.2±0.2°, 20.3±0.2°, 21.7±0.2° and 26.3±0.2°;

or,

wherein the salt is Compound A p-toluenesulfonate;

the molar ratio of Compound A to p-toluenesulfonic acid is 1:1;

the Compound A p-toluenesulfonate is in crystalline form VI;

the crystalline form VI has an XRPD pattern comprising characteristic peaks at diffraction angles (20) of 9.2±0.2°, 10.8±0.2°, 18.0±0.2° and 19.5±0.2°;

or,

wherein the salt is Compound A mesylate;

the molar ratio of Compound A to methanesulfonic acid is 1:1;

the Compound A mesylate is in crystalline form VII;

the crystalline form VII has an XRPD pattern comprising characteristic peaks at diffraction angles (20) of 7.7±0.2°, 10.5±0.2°, 19.0±0.2°, 20.1±0.2° and 20.5±0.2°;

or,

wherein the salt is Compound A mesylate;

the molar ratio of Compound A to methanesulfonic acid is 1:2;

the Compound A mesylate is in crystalline form VIII;

the crystalline form VIII has an XRPD pattern comprising characteristic peaks at diffraction angles (20) of 11.0±0.2°, 12.2±0.2°, 13.4±0.2°, 19.9±0.2°, 20.2±0.2°, 21.4±0.2° and 25.8±0.2°;

or,

wherein the salt is Compound A phosphate;

the molar ratio of Compound A to phosphoric acid is 1:1;

the Compound A phosphate is in crystalline form IX;

the crystalline form IX has an XRPD pattern comprising characteristic peaks at diffraction angles (20) of 7.0±0.2°, 10.7±0.2°, 14.6±0.2° and 26.7±0.2°;

or,

wherein the salt is Compound A maleate;

the molar ratio of Compound A to maleic acid is 1:1;

the Compound A maleate is in crystalline form X;

the crystalline form X has an XRPD pattern comprising characteristic peaks at diffraction angles (20) of 5.4±0.2°, 5.8±0.2°, 13.7±0.2° and 17.1±0.2°;

or,

wherein the salt is Compound A L-tartrate;

the molar ratio of Compound A to L-tartaric acid is 1:1;

the Compound A L-tartrate is in crystalline form XI;

the crystalline form XI has an XRPD pattern comprising characteristic peaks at diffraction angles (20) of 6.5±0.2°, 14.3±0.2°, 20.8±0.2°, 21.5±0.2° and 25.2±0.2°;

or,

wherein the salt is Compound A fumarate;

the molar ratio of Compound A to fumaric acid is 1:1;

the Compound A fumarate is in crystalline form XII;

the crystalline form XII has an XRPD pattern comprising characteristic peaks at diffraction angles (20) of 7.2±0.2°, 10.9±0.2°, 20.9±0.2° and 27.5±0.2°.

5 . A pharmaceutical composition comprising the salt of claim 1 , and one or more pharmaceutically acceptable carriers.

6 . The salt of Compound A according to claim 1 , wherein the crystalline form Ia has an XRPD pattern comprising characteristic peaks at diffraction angles (20) of 7.8±0.2°, 10.4±0.2°, 11.1±0.2°, 15.7±0.2°, 16.2±0.2°, 20.0±0.2°, 20.7±0.2°, 22.3±0.2°, 23.7±0.2°, 24.7±0.2°, 26.0±0.2° and 28.8±0.2°.

7 . The salt of Compound A according to claim 6 , wherein the crystalline form Ia has an XRPD pattern comprising characteristic peaks at diffraction angles (20) of 7.8±0.2°, 10.4±0.2°, 11.1±0.2°, 14.5±0.2°, 14.7±0.2°, 15.7±0.2°, 16.2±0.2°, 18.0±0.2°, 20.0±0.2°, 20.7±0.2°, 22.3±0.2°, 23.0±0.2°, 23.7±0.2°, 24.7±0.2°, 25.3±0.2°, 26.0±0.2°, 26.4±0.2°, 27.0±0.2°, 28.8±0.2°, 29.7±0.2°, 33.9±0.2° and 38.3±0.2°.

8 . The salt of Compound A according to claim 2 , wherein the crystalline form Ib has an XRPD pattern comprising characteristic peaks at diffraction angles (20) of 5.4±0.2°, 9.5±0.2°, 11.2±0.2°, 13.6±0.2°, 20.0±0.2°, 20.8±0.2°, 24.9±0.2° and 25.5±0.2°.

9 . The salt of Compound A according to claim 8 , wherein the crystalline form Ib has an XRPD pattern comprising characteristic peaks at diffraction angles (20) of 5.4±0.2°, 9.5±0.2°, 11.2±0.2°, 13.6±0.2°, 15.7±0.2°, 17.6±0.2°, 20.0±0.2°, 20.8±0.2°, 22.1±0.2°, 23.2±0.2°, 23.6±0.2°, 24.1±0.2°, 24.6±0.2°, 24.9±0.2°, 25.5±0.2° and 30.5±0.2°.

10 . The salt of Compound A according to claim 3 , wherein the crystalline form II has an XRPD pattern comprising characteristic peaks at diffraction angles (20) of 8.2±0.2°, 11.9±0.2°, 13.3±0.2°, 14.2±0.2°, 16.0±0.2°, 18.3±0.2°, 19.4±0.2°, 20.0±0.2°, 21.2±0.2°, 21.9±0.2°, 22.9±0.2°, 24.6±0.2°, 26.6±0.2°, 27.4±0.2° and 28.0±0.2°.

11 . The salt of Compound A according to claim 10 , wherein the crystalline form II has an XRPD pattern comprising characteristic peaks at diffraction angles (20) of 8.2±0.2°, 11.9±0.2°, 13.3±0.2°, 14.2±0.2°, 14.8±0.2°, 16.0±0.2°, 17.8±0.2°, 18.3±0.2°, 19.4±0.2°, 20.0±0.2°, 21.2±0.2°, 21.9±0.2°, 22.6±0.2°, 22.9±0.2°, 23.5±0.2°, 24.6±0.2°, 25.6±0.2°, 26.6±0.2°, 27.4±0.2°, 28.0±0.2°, 29.7±0.2°, 31.8±0.2° and 34.0±0.2°.

12 . The salt of Compound A according to claim 4 , wherein

the crystalline form III has an XRPD pattern comprising characteristic peaks at diffraction angles (20) of 6.9±0.2°, 10.8±0.2°, 14.6±0.2°, 16.3±0.2°, 20.3±0.2°, 22.5±0.2°, 23.4±0.2° and 26.6±0.2°;

the crystalline form IV has an XRPD pattern comprising characteristic peaks at diffraction angles (20) of 8.0±0.2°, 10.5±0.2°, 11.2±0.2°, 20.9±0.2°, 21.8±0.2°, 22.5±0.2°, 23.8±0.2° and 26.3±0.2°;

the crystalline form V has an XRPD pattern comprising characteristic peaks at diffraction angles (20) of 7.9±0.2°, 11.2±0.2°, 20.3±0.2°, 21.7±0.2°, 22.5±0.2°, 23.7±0.2°, 24.8±0.2° and 26.3±0.2°;

the crystalline form VI has an XRPD pattern comprising characteristic peaks at diffraction angles (20) of 9.2±0.2°, 10.8±0.2°, 17.7±0.2°, 18.0±0.2°, 18.5±0.2°, 19.5±0.2°, 20.4±0.2°, 21.7±0.2°, 21.9±0.2°, 23.6±0.2° and 28.6±0.2°;

the crystalline form VII has an XRPD pattern comprising characteristic peaks at diffraction angles (20) of 7.7±0.2°, 10.5±0.2°, 16.2±0.2°, 16.8±0.2°, 19.0±0.2°, 19.9±0.2°, 20.1±0.2°, 20.5±0.2°, 21.0±0.2°, 22.6±0.2°, 24.0±0.2°, 25.5±0.2° and 26.5±0.2°;

the crystalline form VIIl has an XRPD pattern comprising characteristic peaks at diffraction angles (20) of 3.2±0.2°, 6.0±0.2°, 11.0±0.2°, 12.2±0.2°, 13.4±0.2°, 19.9±0.2°, 20.2±0.2°, 21.0±0.2°, 21.4±0.2°, 23.0±0.2°, 23.4±0.2°, 24.9±0.2° and 25.8±0.2°;

the crystalline form IX has an XRPD pattern comprising characteristic peaks at diffraction angles (20) of 7.0±0.2°, 10.7±0.2°, 14.6±0.2°, 15.3±0.2°, 18.4±0.2°, 22.3±0.2°, 23.4±0.2° and 26.7±0.2°;

the crystalline form X has an XRPD pattern comprising characteristic peaks at diffraction angles (20) of 5.4±0.2°, 5.8±0.2°, 8.9±0.2°, 10.0±0.2°, 13.7±0.2°, 16.0±0.2°, 17.1±0.2°, 21.7±0.2° and 21.9±0.2°;

the crystalline form XI has an XRPD pattern comprising characteristic peaks at diffraction angles (20) of 6.5±0.2°, 10.9±0.2°, 12.6±0.2°, 14.3±0.2°, 16.1±0.2°, 17.3±0.2°, 18.0±0.2°, 20.8±0.2°, 21.5±0.2°, 22.5±0.2° and 25.2±0.2°;

the crystalline form XII has an XRPD pattern comprising characteristic peaks at diffraction angles (20) of 7.2±0.2°, 10.3±0.2°, 10.9±0.2°, 15.0±0.2°, 20.9±0.2°, 21.6±0.2°, 24.2±0.2° and 27.5±0.2°.

13 . The salt of Compound A according to claim 12 , wherein

the crystalline form III has an XRPD pattern comprising characteristic peaks at diffraction angles (20) of 6.9±0.2°, 10.8±0.2°, 12.7±0.2°, 14.6±0.2°, 16.3±0.2°, 17.6±0.2°, 18.1±0.2°, 20.3±0.2°, 21.4±0.2°, 22.5±0.2°, 23.4±0.2°, 24.2±0.2°, 25.5±0.2°, 26.0±0.2°, 26.6±0.2° and 27.1±0.2°;

the crystalline form IV has an XRPD pattern comprising characteristic peaks at diffraction angles (20) of 8.0±0.2°, 10.5±0.2°, 11.2±0.2°, 13.2±0.2°, 15.3±0.2°, 15.9±0.2°, 16.8±0.2°, 19.0±0.2°, 20.9±0.2°, 21.8±0.2°, 22.5±0.2°, 23.8±0.2°, 24.9±0.2°, 26.3±0.2°, 28.3±0.2°, 29.1±0.2°, 30.1±0.2° and 37.9±0.2°

the crystalline form V has an XRPD pattern comprising characteristic peaks at diffraction angles (20) of 7.9±0.2°, 10.4±0.2°, 11.2±0.2°, 13.1±0.2°, 15.1±0.2°, 15.7±0.2°, 15.9±0.2°, 16.6±0.2°, 18.9±0.2°, 20.3±0.2°, 21.0±0.2°, 21.7±0.2°, 22.5±0.2°, 23.7±0.2°, 24.3±0.2°, 24.8±0.2°, 26.3±0.2°, 28.2±0.2°, 29.1±0.2°, 30.1±0.2° and 37.9±0.2°;

the crystalline form VI has an XRPD pattern comprising characteristic peaks at diffraction angles (20) of 9.2±0.2°, 10.8±0.2°, 14.9±0.2°, 15.4±0.2°, 17.7±0.2°, 18.0±0.2°, 18.5±0.2°, 19.5±0.2°, 20.4±0.2°, 21.2±0.2°, 21.7±0.2°, 21.9±0.2°, 23.6±0.2°, 24.5±0.2°, 26.2±0.2°, 28.6±0.2°, 32.1±0.2° and 32.7±0.2°;

the crystalline form VII has an XRPD pattern comprising characteristic peaks at diffraction angles (20) of 6.0±0.2°, 7.7±0.2°, 10.5±0.2°, 11.0±0.2°, 12.3±0.2°, 13.5±0.2°, 14.0±0.2°, 14.3±0.2°, 14.9±0.2°, 15.5±0.2°, 16.2±0.2°, 16.8±0.2°, 19.0±0.2°, 19.9±0.2°, 20.1±0.2°, 20.5±0.2°, 21.0±0.2°, 21.4±0.2°, 22.6±0.2°, 23.2±0.2°, 24.0±0.2°, 24.9±0.2°, 25.5±0.2°, 25.8±0.2°, 26.5±0.2°, 27.6±0.2° and 29.6±0.2°;

the crystalline form VIII has an XRPD pattern comprising characteristic peaks at diffraction angles (20) of 3.2±0.2°, 6.0±0.2°, 9.4±0.2°, 11.0±0.2°, 12.2±0.2°, 13.4±0.2°, 14.9±0.2°, 15.5±0.2°, 15.7±0.2°, 17.7±0.2°, 18.1±0.2°, 18.9±0.2°, 19.9±0.2°, 20.2±0.2°, 21.0±0.2°, 21.4±0.2°, 21.9±0.2°, 22.4±0.2°, 23.0±0.2°, 23.4±0.2°, 23.9±0.2°, 24.9±0.2°, 25.2±0.2°, 25.8±0.2°, 26.5±0.2°, 27.4±0.2°, 28.9±0.2°, 30.8±0.2° and 31.5±0.2°;

the crystalline form IX has an XRPD pattern comprising characteristic peaks at diffraction angles (20) of 7.0±0.2°, 10.7±0.2°, 14.0±0.2°, 14.6±0.2°, 15.3±0.2°, 16.2±0.2°, 18.4±0.2°, 20.3±0.2°, 21.5±0.2°, 22.3±0.2°, 23.4±0.2°, 24.3±0.2°, 25.7±0.2°, 26.7±0.2° and 29.5±0.2°;

the crystalline form X has an XRPD pattern comprising characteristic peaks at diffraction angles (20) of 5.4±0.2°, 5.8±0.2°, 8.9±0.2°, 10.0±0.2°, 13.7±0.2°, 16.0±0.2°, 17.1±0.2°, 21.7±0.2°, 21.9±0.2°, 24.1±0.2°, 25.8±0.2° and 27.6±0.2°;

the crystalline form XI has an XRPD pattern comprising characteristic peaks at diffraction angles (20) of 6.5±0.2°, 10.3±0.2°, 10.9±0.2°, 12.6±0.2°, 14.3±0.2°, 15.2±0.2°, 16.1±0.2°, 17.3±0.2°, 18.0±0.2°, 19.4±0.2°, 20.8±0.2°, 21.5±0.2°, 22.0±0.2°, 22.5±0.2°, 23.4±0.2°, 23.8±0.2°, 24.2±0.2°, 24.8±0.2°, 25.2±0.2°, 25.8±0.2°, 26.7±0.2°, 27.8±0.2°, 28.8±0.2°, 30.1±0.2°, 31.4±0.2°, 33.8±0.2° and 35.2±0.2°;

the crystalline form XII has an XRPD pattern comprising characteristic peaks at diffraction angles (20) of 7.2±0.2°, 7.8±0.2°, 10.3±0.2°, 10.9±0.2°, 13.0±0.2°, 14.5±0.2°, 15.0±0.2°, 17.6±0.2°, 20.9±0.2°, 21.6±0.2°, 22.9±0.2°, 24.2±0.2°, 25.9±0.2°, 27.5±0.2° and 31.0±0.2°.

14 . A pharmaceutical composition comprising the salt of claim 2 , and one or more pharmaceutically acceptable carriers.

15 . A pharmaceutical composition comprising the salt of claim 3 , and one or more pharmaceutically acceptable carriers.

16 . A pharmaceutical composition comprising the salt of claim 4 , and one or more pharmaceutically acceptable carriers.

Assignments (1)

Priority Claims (1)

Continuity (1)

References Cited (11)