TLR7 AGONIST CRYSTALLINE FORM A, PREPARATION METHOD AND USE THEREOF

• US 20190040071A1
• Filed: 02/04/2017
• Published: 02/07/2019
• Est. Priority Date: 02/05/2016
• Status: Active Grant

• Current Assignee: Chia Tai Tianqing Pharmaceutical Group Co. Ltd. (SINO Biopharmaceutical Limited)
• Original Assignee: Chia Tai Tianqing Pharmaceutical Group Co. Ltd. (SINO Biopharmaceutical Limited)
• Inventors: DING, Zhaozhong, SUN, Fei, HU, Yinghu, ZHOU, Yilong, WANG, Zheng, ZHAO, Rui, YANG, Ling
• Granted Patent: US 10,442,811 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: C07B 2200/13 Crystalline forms, e.g. polymorphs
• CPC Class Codes: C07D 487/04 Ortho-condensed systems

Abstract

The present invention relates to crystalline form A of a TLR7 agonist 2-butoxy-7-(4-(pyrrolidin-1-ylmethyl)-benzyl)-5H-pyrrolo[3,2-d]pyrimidin-4-amine (formula I), a method for preparing the crystalline form A, and the use thereof.

Claims

1. A crystal form A of the compound of formula I

2. The crystal form A of the compound of formula I according to claim 1, wherein the crystal form A has the following cell parameters:

a=16.560 (3) Å

b=10.426 (2) Å

c=12.203 (2) Å

α

=90°

β

=98.54(3)°

γ

=90°

Space groups;

P21/c

Z=4.

3. The crystal form A of the compound of formula I according to claim 1, wherein when characterized by DSC, the initial temperature is 199.0°

C.±

5°

C. and the peak temperature is 200.4°

C.±

5°

C.

4. A process for preparing the crystal form A of the compound of formula I according to claim 1, comprising the following steps:

1) dissolving the compound of formula I in a crystallizing solvent, which is preferably heated to promote dissolution; and

2) cooling for crystallization, filtering, washing and drying to obtain the crystal form A.

5. The preparing process according to claim 4, wherein the crystallizing solvent in step 1) is selected from the group consisting of methanol, ethanol, propanol, isopropanol, n-butanol, isobutanol, tertiary butanol, acetone, ethyl acetate, water and mixed solvent thereof, preferably ethanol.

6. The preparing process according to claim 4, wherein in step 1), the amount of crystallizing solvent added per 1 g of the compound of formula I is 2 to 10 mL, preferably 4 to 8 mL, more preferably 5 to 7 mL.

7. The preparing process according to claim 4, wherein in step 1), the heating temperature is 40°

C. to 90°

C., preferably 50°

C. to 80°

C., more preferably 70°

C. to 80°

C.

8. A crystalline composition, wherein based on the weight of the crystalline composition, the crystal form A of the compound of formula I according to claim 1 is 50% or more, preferably 80% or more, more preferably 90% or more, and most preferably 95% or more.

9. A pharmaceutical composition, comprising the crystal form A of the compound of formula I according to claim 1 in an effective amount.

10. A method for treating Toll-like receptor 7 associated disease comprising administering a subject in need thereof the crystal form A of the compound of formula I according to claim 1.

11. A pharmaceutical composition, comprising the crystalline composition according to claim 8 in an effective amount.

12. A method for treating Toll-like receptor 7 associated disease comprising administering a subject in need thereof the crystalline composition according to claim 8.

13. A method for treating Toll-like receptor 7 associated disease comprising administering a subject in need thereof the pharmaceutical composition according to claim 9.

14. The method according to claim 10, wherein the disease is virus infection.

15. The method according to claim 12, wherein the disease is virus infection.

16. The method according to claim 13, wherein the disease is virus infection.