Crystalline forms of a neuroactive steroid

Patent metadata

Field	Value
Publication number	US-2024218012-A1
Application number	US-202418597990-A
Country	US
Kind code	A1
Filing date	Mar 7, 2024
Priority date	Jul 28, 2021
Publication date	Jul 4, 2024
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 8.9±0.3, 14.6±0.3, 16.4±0.3, 18.0±0.3, and 20.0±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 11.6±0.3, 15.0±0.3, 17.4±0.3, 21.2±0.3 and 29.0±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 160° C. to about 166° 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 200.2±0.3 ppm, 199.1±0.3 ppm, 162.8±0.3 ppm, 82.9±0.3 ppm, 82.1±0.3, and 12.6±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 70.4±0.3 ppm, 63.6±0.3 ppm, 49.7±0.3 ppm, 35.5±0.3 ppm, and 15.5±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 62.9±0.3 ppm, 61.4±0.3 ppm, 60.6±0.3 ppm, 45.4±0.3 ppm, and 37.9±0.3 ppm in a 13 C SSNMR spectrum.

42 . A pharmaceutical composition comprising a crystalline form of claim 36 , and a pharmaceutically acceptable excipient.

Assignees

• Sage Therapeutics Inc

Inventors

• Kuang Shanming
• Li Tianrui

Classifications

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• A61P25/30

  for treating abuse or dependence · CPC title

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title

• A61P25/20

  Hypnotics; Sedatives · CPC title

• A61P25/04

  Centrally acting analgesics, e.g. opioids · CPC title