Solid forms of a toll-like receptor modulator

Patent metadata

Field	Value
Publication number	US-9738646-B2
Application number	US-201514853855-A
Country	US
Kind code	B2
Filing date	Sep 14, 2015
Priority date	Sep 16, 2014
Publication date	Aug 22, 2017
Grant date	Aug 22, 2017

Abstract

The present invention provides crystalline forms, solvates and hydrates of 4-amino-2-butoxy-8-(3-(pyrrolidin-1-ylmethyl)benzyl)-7,8-dihydropteridin-6(5H)-one, and methods of making.

First claim

What is claimed is:

1. A crystalline form of Compound I having the structure:

characterized by an XRPD pattern comprising three peaks at 5.8, 11.4, 11.6, 17.7, 20.1, 20.9, 22.3, 23.9, 26.0 or 26.8 degrees 2θ (±0.2 degrees 2θ), wherein the XRPD is made using CuK α1 radiation.

2. The crystalline form of claim 1 , characterized by an X-ray powder diffraction (XRPD) pattern further comprising four peaks at 5.8, 11.4, 11.6, 17.7, 20.1, 20.9, 22.3, 23.9, 26.0 or 26.8 degrees 2θ (±0.2 degrees 2θ) wherein the XRPD is made using CuK α1 radiation.

3. The crystalline form of claim 1 , characterized by an XRPD pattern comprising peaks at 5.8, 11.4, 11.6, 17.7, 20.1, 20.9, 22.3, 23.9, 26.0 and 26.8 degrees 2θ (±0.2 degrees 2θ), wherein the XRPD is made using CuK α1 radiation.

4. The crystalline form of claim 1 , characterized by the XRPD pattern substantially in accordance with that of FIG. 1 .

5. The crystalline form of claim 1 , characterized by one or more differential scanning calorimetry (DSC) endotherms at about 133° C. or about 170° C.

6. The crystalline form of any of claim 1 , characterized by DSC endotherms at about 133° C. and about 170° C.

7. A method of preparing the crystalline form of Compound I of claim 1 , comprising:
forming a mixture comprising Compound I, and a solvent comprising a C 1 -C 3 alcohol and dichloromethane, and evaporating the solvent, thereby forming the crystalline form of Compound I of claim 1 .

8. The method of claim 7 , wherein the solvent comprises one of methanol, ethanol, or isopropanol.

9. The method of claim 7 , wherein the solvent comprises methanol and dichloromethane.

10. A pharmaceutical composition comprising a therapeutically effective amount of the crystalline form of Compound I of claim 1 , and a pharmaceutically acceptable carrier or excipient.

11. The crystalline form of claim 1 , characterized by an X-ray powder diffraction (XRPD) pattern comprising five peaks at 5.8, 11.4, 11.6, 17.7, 20.1, 20.9, 22.3, 23.9, 26.0 or 26.8 degrees 2θ (±0.2 degrees 2θ) wherein the XRPD is made using CuK α1 radiation.

12. The crystalline form of claim 1 , characterized by an X-ray powder diffraction (XRPD) pattern comprising six peaks at 5.8, 11.4, 11.6, 17.7, 20.1, 20.9, 22.3, 23.9, 26.0 or 26.8 degrees 2θ (±0.2 degrees 2θ) wherein the XRPD is made using CuK α1 radiation.

13. A crystalline form of Compound I having the structure:

characterized by an XRPD pattern comprising peaks at 5.8, 11.6 and 22.3 degrees 2θ (±0.2 degrees 2θ), wherein the XRPD is made using CuK α1 radiation.

14. The crystalline form of claim 13 , characterized by an X-ray powder diffraction (XRPD) pattern further comprising an additional peak at 17.7, 23.9 or 26.0 degrees 2θ (±0.2 degrees 2θ), wherein the XRPD is made using CuK α1 radiation.

15. The crystalline form of claim 13 , characterized by an X-ray powder diffraction (XRPD) pattern further comprising two additional peaks at 17.7, 23.9 or 26.0 degrees 2θ (±0.2 degrees 2θ), wherein the XRPD is made using CuK α1 radiation.

16. The crystalline form of claim 13 , characterized by an XRPD pattern comprising peaks at 5.8, 11.6, 17.7, 20.1, 20.9, 22.3, 23.9, 26.0 and 26.8 degrees 2θ (±0.2 degrees 2θ), wherein the XRPD is made using CuK α1 radiation.

17. A pharmaceutical composition comprising a therapeutically effective amount of the crystalline form of Compound I of claim 13 , and a pharmaceutically acceptable carrier or excipient.

18. A crystalline form of Compound I having the structure:

characterized by an XRPD pattern comprising peaks at 5.8, 11.6, 22.3, and 23.9 degrees 2θ (±0.2 degrees 2θ), wherein the XRPD is made using CuK α1 radiation.

19. The crystalline form of claim 18 , characterized by an XRPD pattern comprising peaks at 5.8, 11.6, 17.7, 22.3, 23.9, 26.0 and 26.8 degrees 2θ (±0.2 degrees 2θ), wherein the XRPD is made using CuK α1 radiation.

20. A pharmaceutical composition comprising a therapeutically effective amount of the crystalline form of Compound I of claim 18 , and a pharmaceutically acceptable carrier or excipient.

Assignees

• Gilead Sciences Inc

Inventors

• Brown Brandon Heath
• Roethle Paul

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P31/20

  for DNA viruses · CPC title

• A61P31/18

  for HIV · CPC title

• A61P31/14

  for RNA viruses · CPC title

• A61P37/04

  Immunostimulants · CPC title