Salts or co-crystals of {2-[3-cyclohexyl-3-(trans-4-propoxy-cyclohexyl)-ureido]-thiazol-5-ylsulfanyl}-acetic acid and uses thereof

Patent metadata

Field	Value
Publication number	US-12479808-B2
Application number	US-202118000907-A
Country	US
Kind code	B2
Filing date	Jun 7, 2021
Priority date	Jun 8, 2020
Publication date	Nov 25, 2025
Grant date	Nov 25, 2025

Abstract

Sodium, piperazine, and hydrochloride salts or co-crystals of {2-[3-cyclohexyl-3-(trans-4-propoxy-cyclohexyl)-ureido]-thiazol-5-ylsulfanyl}-acetic acid (“Compound 1”) are provided herein.

First claim

What is claimed is:

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.

Assignees

• Vtv Therapeutics Llc

Inventors

• Teng Jing
• Gignac Nathan E

Classifications

• C07D295/00

  Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61K31/426

  1,3-Thiazoles · CPC title

• A61K31/495

  having six-membered rings with two {or more} nitrogen atoms as the only ring heteroatoms, e.g. piperazine {or tetrazines}(A61K31/48 takes precedence {; with three nitrogen atoms A61K31/53}) · CPC title