Salt forms and polymorphs of (R)-1-(4-(6-(2-(4-(3,3-difluorocyclobutoxy)-6-methylpyrdin-2-yl)acetamido) pyridazin-3-yl)-2-fluorobutyl)-N-methyl-1H-1,2,3-triazole-4-carboxamide

Patent metadata

Field	Value
Publication number	US-10150753-B2
Application number	US-201615387560-A
Country	US
Kind code	B2
Filing date	Dec 21, 2016
Priority date	Dec 22, 2015
Publication date	Dec 11, 2018
Grant date	Dec 11, 2018

Abstract

Disclosed herein is the compound (R)-1-(4-(6-(2-(4-(3,3-difluorocyclobutoxy)-6-methylpyridin-2-yl)acetamido)pyridazin-3-yl)-2-fluorobutyl)-N-methyl-1H-1,2,3-triazole-4-carboxamide, and salt forms and polymorphs thereof demonstrating improved exposure after oral dosing. Methods of inhibition GLS1 activity in a human or animal subject are also provided.

First claim

What is claimed is:

1. The compound

or a salt, solvate, or polymorph thereof.

2. A salt as recited in claim 1 , of structural Formula I:

or a polymorph thereof, wherein:
R − is chosen from C1 − , Br − , I − ,HSO 4 − , SO 4 2− , NO 3 − , CH 3 SO 3 − , PhSO 3 − , 4-MePhSO 3 − , NaphthaleneSO 3 − ;
n is an integer from 0 to 2; and
Y is an optional solvate.

3. The solid compound

or a polymorph thereof.

4. The solid compound as recited in claim 3 , which is crystalline.

5. Polymorph A of the solid compound as recited in claim 3 .

6. Polymorph B of the solid compound as recited in claim 3 .

7. Polymorph C of the solid compound as recited in claim 3 .

8. Polymorph D of the solid compound as recited in claim 3 .

9. The polymorph D as recited in claim 8 , having one or more x-ray powder diffraction peaks chosen from about 4.0, about 8.0, about 11.6, about 11.9, about 14.9, about 15.9, about 17.6, about 19.9, about 20.2, about 22.4, about 23.7, and about 23.9 degress 2-theta.

10. The Polymorph D as recited in claim 9 , which comprises three or more of the peaks.

11. The Polymorph D as recited in claim 9 , which comprises five or more of the peaks.

12. The Polymorph D as recited in claim 8 , wherein said polymorph displays an endothermic peak in DSC with onset of 197° C.±1° C.

13. The Polymorph D as recited in claim 8 , wherein said polymorph is anhydrous.

14. The Polymorph D as recited in claim 8 , wherein said polymorph displays weight loss in DSC of less than 1% from 30° C. to 200° C.

15. A composition comprising a compound or polymorph of claim 3 , and a pharmaceutically acceptable carrier, adjuvant, or vehicle.

Assignees

• Univ Texas

Inventors

• Jones Philip
• Soth Michael J
• Burke Jason P
• Le Kang
• Liu Gang

Classifications

• A61K31/501 Primary

  not condensed and containing further heterocyclic rings · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61K31/337

  having four-membered rings, e.g. taxol · CPC title