Granted Patent B2

US 12,479,808 · App. 18/000,907 · Granted Nov 25, 2025

Inventors: Jing Teng (Lafayette, IN); Nathan E. Gignac (Lafayette, IN)

Assignee: VTV THERAPEUTICS LLC

C07D277/54A61P3/10C07D295/00C07B2200/13

Abstract

Claims (50)

1 . A crystalline form of the sodium salt, piperazine salt, or hydrochloride salt of {2-[3-cyclohexyl-3-(trans-4-propoxy-cyclohexyl)-ureido]-thiazol-5-ylsulfanyl}-acetic acid, wherein:

(a) the sodium salt of {2-[3-cyclohexyl-3-(trans-4-propoxy-cyclohexyl)-ureido]-thiazol-5-ylsulfanyl}-acetic acid salt is characterized as having an X-ray powder diffraction (XRPD) pattern with peaks at the following diffraction angles 4.4±0.2, 9.4±0.2, and 20.0±0.2 degrees two theta as measured using Cu, Kα radiation (Form A);

(b) the piperazine salt of {2-[3-cyclohexyl-3-(trans-4-propoxy-cyclohexyl)-ureido]-thiazol-5-ylsulfanyl}-acetic acid salt is characterized as having an XRPD pattern comprising peaks at the following diffraction angles 4.9±0.2, 12.5±0.2, and 14.9±0.2 degrees two theta as measured using Cu, Kα radiation (Form B);

(c) the piperazine salt of {2-[3-cyclohexyl-3-(trans-4-propoxy-cyclohexyl)-ureido]-thiazol-5-ylsulfanyl}-acetic acid salt is characterized as having an XRPD pattern comprising peaks at the following diffraction angles 5.1±0.2, 13.6±0.2, and 20.5±0.2 degrees two theta as measured using Cu, Kα radiation (Form C) of Formula (I);

(d) the piperazine salt of {2-[3-cyclohexyl-3-(trans-4-propoxy-cyclohexyl)-ureido]-thiazol-5-ylsulfanyl}-acetic acid salt is characterized as having an XRPD pattern comprising peaks at the following diffraction angles 5.5±0.2, 16.7±0.2, and 19.9±0.2 degrees two theta as measured using Cu, Kα radiation (Form D) of Formula (I);

(e) the piperazine salt of {2-[3-cyclohexyl-3-(trans-4-propoxy-cyclohexyl)-ureido]-thiazol-5-ylsulfanyl}-acetic acid salt is characterized as having an XRPD pattern comprising peaks at the following diffraction angles 4.9±0.2, 12.5±0.2, and 18.3±0.2 degrees two theta as measured using Cu, Kα radiation (Form E); or

(f) the hydrochloride salt of {2-[3-cyclohexyl-3-(trans-4-propoxy-cyclohexyl)-ureido]-thiazol-5-ylsulfanyl}-acetic acid salt is characterized as having an XRPD pattern comprising peaks at the following diffraction angles 4.6±0.2, 7.2°±0.2, and 17.7°±0.2 degrees two theta as measured using Cu, Kα radiation (Form F).

2 . The crystalline form of the sodium salt of claim 1 that is characterized as having an X-ray powder diffraction (XRPD) pattern with peaks at the following diffraction angles 4.4±0.2, 9.4±0.2, and 20.0±0.2 degrees two theta as measured using Cu, Kα radiation (Form A).

3 . The crystalline form of the sodium salt of claim 2 that is further characterized as having an endothermic peak with onset at 216° C.±2° C., as determined by DSC; or an IR pattern having peaks at 1358.3±2.0, 1606.1±2.0, and 1649.0±2.0 cm −1 .

4 . The crystalline form of the piperazine salt of claim 1 that is characterized as having an XRPD pattern comprising peaks at the following diffraction angles 4.9±0.2, 12.5±0.2, and 14.9±0.2 degrees two theta as measured using Cu, Kα radiation (Form B).

5 . The crystalline form of the piperazine salt of claim 4 that is further characterized as having an endothermic peak with onset at 226° C.±2° C., as determined by DSC.

6 . The crystalline form of the piperazine salt of claim 1 that is characterized as having an XRPD pattern comprising peaks at the following diffraction angles 5.1±0.2, 13.6±0.2, and 20.5±0.2 degrees two theta as measured using Cu, Kα radiation (Form C).

7 . The crystalline form of the piperazine salt of claim 6 that is further characterized as having an endothermic peak with onset at 214° C.±2° C., as determined by DSC.

8 . The crystalline form of the piperazine salt of claim 1 that is characterized as having an XRPD pattern comprising peaks at the following diffraction angles 5.5±0.2, 16.7±0.2, and 19.9±0.2 degrees two theta as measured using Cu, Kα radiation (Form D).

9 . The crystalline form of the piperazine salt of claim 1 that is characterized as having an XRPD pattern comprising peaks at the following diffraction angles 4.9±0.2, 12.5±0.2, and 18.3±0.2 degrees two theta as measured using Cu, Kα radiation (Form E).

10 . The crystalline form of the piperazine salt of claim 9 that is further characterized as having an endothermic peak with onset at 221° C.±2° C., as determined by DSC.

11 . The crystalline form of the hydrochloride salt of claim 1 that is characterized as having an XRPD pattern comprising peaks at the following diffraction angles 4.6±0.2, 7.2°±0.2, and 17.7°±0.2 degrees two theta as measured using Cu, Kα radiation (Form F).

12 . The crystalline form of the hydrochloride salt of claim 11 that is further characterized as having an IR pattern having peaks at 1119.0±2.0, 1540.2±2.0, and 1667.5±2.0 cm −1 .

13 . A crystalline form of the sodium salt, piperazine salt, or hydrochloride salt of {2-[3-cyclohexyl-3-(trans-4-propoxy-cyclohexyl)-ureido]-thiazol-5-ylsulfanyl}-acetic acid, wherein:

(a) the sodium salt of {2-[3-cyclohexyl-3-(trans-4-propoxy-cyclohexyl)-ureido]-thiazol-5-ylsulfanyl}-acetic acid salt is characterized as having an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 1 as measured using Cu, Kα radiation (Form A);

(b) the piperazine salt of {2-[3-cyclohexyl-3-(trans-4-propoxy-cyclohexyl)-ureido]-thiazol-5-ylsulfanyl}-acetic acid salt is characterized as having an XRPD pattern substantially the same as shown in FIG. 5 as measured using Cu, Kα radiation (Form B);

(c) the piperazine salt of {2-[3-cyclohexyl-3-(trans-4-propoxy-cyclohexyl)-ureido]-thiazol-5-ylsulfanyl}-acetic acid salt is characterized as having an XRPD pattern substantially the same as shown in FIG. 9 as measured using Cu, Kα radiation (Form C) of Formula (I);

(d) the piperazine salt of {2-[3-cyclohexyl-3-(trans-4-propoxy-cyclohexyl)-ureido]-thiazol-5-ylsulfanyl}-acetic acid salt is characterized as having an XRPD pattern substantially the same as shown in FIG. 12 as measured using Cu, Kα radiation (Form D) of Formula (I);

(e) the piperazine salt of {2-[3-cyclohexyl-3-(trans-4-propoxy-cyclohexyl)-ureido]-thiazol-5-ylsulfanyl}-acetic acid salt is characterized as having an XRPD pattern substantially the same as shown in FIG. 13 as measured using Cu, Kα radiation (Form E); or

(f) the hydrochloride salt of {2-[3-cyclohexyl-3-(trans-4-propoxy-cyclohexyl)-ureido]-thiazol-5-ylsulfanyl}-acetic acid salt is characterized as having an XRPD pattern substantially the same as shown in FIG. 16 as measured using Cu, Kα radiation (Form F).

14 . The crystalline form of the sodium salt of claim 13 that is characterized as having an (XRPD pattern substantially the same as shown in FIG. 1 as measured using Cu, Kα radiation (Form A).

15 . The crystalline form of the sodium salt of claim 14 that is further characterized as having an a TGA profile substantially the same as shown in FIG. 2 ; or

a DSC profile substantially the same as shown in FIG. 3 ; or

an IR pattern substantially the same as shown in FIG. 4 .

16 . The crystalline form of the piperazine salt of claim 13 that is characterized as having an XRPD pattern substantially the same as shown in FIG. as measured using Cu, Kα radiation (Form B).

17 . The crystalline form of the piperazine salt of claim 4 that is further characterized as having an a TGA profile substantially the same as shown in FIG. 6 ; or

a DSC profile substantially the same as shown in FIG. 7 ; or

a 13 C NMR substantially the same as shown in FIG. 8 .

18 . The crystalline form of the piperazine salt of claim 13 that is characterized as having an XRPD pattern substantially the same as shown in FIG. 9 as measured using Cu, Kα radiation (Form C).

19 . The crystalline form of the piperazine salt of claim 18 that is further characterized as having a TGA profile substantially the same as shown in FIG. 10 ; or

a DSC profile substantially the same as shown in FIG. 11 .

20 . The crystalline form of the piperazine salt of claim 13 that is characterized as having an XRPD pattern substantially the same as shown in FIG. 12 as measured using Cu, Kα radiation (Form D).

21 . The crystalline form of the piperazine salt of claim 13 that is characterized as having an XRPD pattern substantially the same as shown in FIG. 13 as measured using Cu, Kα radiation (Form E).

22 . The crystalline form of the piperazine salt of claim 21 that is further characterized as having

a TGA profile substantially the same as shown in FIG. 14 ; or

a DSC profile substantially the same as shown in FIG. 15 .

23 . The crystalline form of the hydrochloride salt of claim 13 that is characterized as having an XRPD pattern substantially the same as shown in FIG. 16 as measured using Cu, Kα radiation (Form F).

24 . The crystalline form of the hydrochloride salt of claim 23 that is further characterized as having

a TGA profile substantially the same as shown in FIG. 17 ; or

a DSC profile substantially the same as shown in FIG. 18 ; or

an IR pattern substantially the same as shown in FIG. 19 .

25 . A pharmaceutical composition comprising the crystalline form of claim 1 and a pharmaceutically acceptable carrier, diluent, or excipient, or a mixture thereof.

26 . A pharmaceutical composition comprising the crystalline form of claim 13 and a pharmaceutically acceptable carrier, diluent, or excipient, or a mixture thereof.

27 . A method of treating a type of diabetes mellitus type 1 or type 2 in a patient in need thereof, where the method comprises administering to the patient the pharmaceutical composition of claim 25 .

28 . A method of treating a type of diabetes mellitus type 1 or type 2 in a patient in need thereof, where the method comprises administering to the patient the pharmaceutical composition of claim 26 .

Assignments (2)

Continuity (2)

References Cited (213)