Crystalline forms of a neuroactive steroid

Patent metadata

Field	Value
Publication number	US-2023374061-A1
Application number	US-202318363942-A
Country	US
Kind code	A1
Filing date	Aug 2, 2023
Priority date	Jul 28, 2021
Publication date	Nov 23, 2023
Grant date	—

Abstract

This invention relates to crystalline forms of anhydrous Compound (1) and pharmaceutical compositions thereof. Also disclosed herein are methods of making crystalline solid forms of Compound (1), and methods of using the crystalline forms of Compound (1) and pharmaceutical compositions thereof for modulating GABA activity (e.g., positive allosteric modulation of GABA activity) and treating CNS-related disorders.

First claim

1 - 35 . (canceled)

36 . A crystalline form of Compound (1), wherein Compound (1) is represented by the following structural formula:

wherein the crystalline form is crystalline anhydrous Compound (1), and wherein the crystalline form is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 15.4±0.3, 15.6±0.3, 18.1±0.3, 18.8±0.3, and 22.6±0.3 in an X-ray powder diffraction pattern.

37 . The crystalline form of claim 36 , wherein the crystalline form is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 9.4±0.3, 11.9±0.3, 22.2±0.3, and 23.4±0.3 in an X-ray powder diffraction pattern.

38 . The crystalline form of claim 36 , wherein the crystalline form has an endotherm at a T onset from about 146° C. to about 157° C. when heated at a rate of 10° C./min starting at a temperature of about 30° C.

39 . The crystalline form of claim 36 , wherein the crystalline form is characterized by one or more peaks corresponding to 200.0±0.3 ppm, 164.3±0.3 ppm, 81.3±0.3 ppm, 70.5±0.3 ppm, and 62.2±0.3 ppm in a 13 C SSNMR spectrum.

40 . The crystalline form of claim 39 , wherein the crystalline form is further characterized by one or more peaks corresponding to 60.9±0.3 ppm, 60.0±0.3 ppm, 56.7±0.3 ppm, 47.8±0.3 ppm, and 45.9±0.3 ppm in a 13 C SSNMR spectrum.

41 . The crystalline form of claim 40 , wherein the crystalline form is further characterized by one or more peaks corresponding to 42.6±0.3 ppm, 39.3±0.3 ppm, 38.3±0.3 ppm, 35.5±0.3 ppm, 25.8±0.3 ppm, and 22.9±0.3 ppm in a 13 C SSNMR spectrum.

42 . A pharmaceutical composition comprising a crystalline form of any one of claims 36 - 41 , and a pharmaceutically acceptable excipient.

Assignees

• Sage Therapeutics Inc

Inventors

• Kuang Shanming
• Li Tianrui

Classifications

• C07J43/003 Primary

  not condensed · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• A61P25/00 Primary

  Drugs for disorders of the nervous system · CPC title

• A61P25/18

  Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia · CPC title

• A61P25/08

  Antiepileptics; Anticonvulsants · CPC title