CRYSTALLINE FORM OF OREXIN RECEPTOR ANTAGONIST, PROCESSES FOR PREPARATION THEREOF AND USE THEREOF

• US 20200190060A1
• Filed: 01/30/2020
• Published: 06/18/2020
• Est. Priority Date: 08/01/2017
• Status: Active Grant

• Current Assignee: Bergen Pharmaceutical LLC
• Original Assignee: Crystal Pharmaceutical (Suzhou) Co., Ltd. (Crystal Pharmatech Co. Ltd.)
• Inventors: Chen, Minhua, Zhang, Yanfeng, Huang, Chunxiang, Zhang, Xiaoyu
• Granted Patent: US 10,759,779 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 31/506 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives
• CPC Class Codes: C07B 2200/13 Crystalline forms, e.g. polymorphs
• CPC Class Codes: C07D 239/34 One oxygen atom
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links

Abstract

The present disclosure provides a novel crystalline form of Lemborexant and processes for preparation thereof. Pharmaceutical composition containing Lemborexant, and use of Lemborexant for preparing orexin receptor antagonist drug, and use of Lemborexant for preparing drugs treating insomnia and irregular sleep-wake rhythm disorder are also provided. The crystalline form of the present disclosure have one or more improved properties compared with crystalline forms of prior arts, and has significant values for future drug optimization and development.

Claims

1. A crystalline form CS2 of E-2006, wherein the X-ray powder diffraction pattern shows characteristic peaks at 2theta values of 7.8°

±

0.2°

, 15.6°

±

0.2° and

11.4°

±

0.2°

using CuKα

radiation.

2. The crystalline form CS2 according to claim 1, wherein the X-ray powder diffraction pattern shows one or two or three characteristic peaks at 2theta values of 12.5°

±

0.2°

, 21.3°

±

0.2° and

27.3°

±

0.2°

using CuKα

radiation.

3. The crystalline form CS2 according to claim 1, wherein the X-ray powder diffraction pattern shows one or two or three characteristic peaks at 2theta values of 24.0°

±

0.2°

, 19.4°

±

0.2° and

22.3°

±

0.2°

using CuKα

radiation.

4. A process for preparing crystalline form CS2 according to claim 1, wherein the process comprises:

(1) Dissolving compound (I) in a solvent to get a solution containing compound (I), then adding an anti-solvent to the solution slowly, stirring and crystallization to obtain crystalline form CS2;

or

(2) Dissolving compound (I) in ketones and slowly evaporating to obtain crystalline form CS2;

or

(3) Dissolving compound (I) in nitriles, adding an ionic liquid, then slowly evaporating to obtain crystalline form CS2.

5. The process for preparing crystalline form CS2 according to claim 4, wherein in method (1), said solvent is alcohol, said anti-solvent is water;

in method (2), said ketone is acetone;

in method (3), said nitrile is acetonitrile, said ionic liquid is 1-ethyl-3-methylimidazolium methyl sulfate, or 1-ethyl-3-methylimidazolium hexafluoroantimonate, or 1,3-dimethylimidazolium dimethyl phosphate.

6. The process for preparing crystalline form CS2 according to claim 5, wherein in method (1) said alcohol is methanol.

7. A pharmaceutical composition, said pharmaceutical composition comprises a therapeutically effective amount of crystalline form CS2 according to claim 1 and pharmaceutically acceptable carriers, diluents or excipients.

9. A method of treating insomnia and/or irregular sleep-wake rhythm disorder, comprising administering to a patient in need thereof a therapeutically effective amount of crystalline form CS2 according to claim 1.

8. (canceled)