Neuroactive steroids, compositions, and uses thereof

Patent metadata

Field	Value
Publication number	US-10323059-B2
Application number	US-201715698151-A
Country	US
Kind code	B2
Filing date	Sep 7, 2017
Priority date	Jul 19, 2013
Publication date	Jun 18, 2019
Grant date	Jun 18, 2019

Abstract

Described herein are neuroactive steroids of the Formula (I):

or a pharmaceutically acceptable salt thereof; wherein R 1a and R 1b are as defined herein. Such compounds are envisioned, in certain embodiments, to behave as GABA modulators. The present invention also provides pharmaceutical compositions comprising a compound of the present invention and methods of use and treatment, e.g., such for inducing sedation and/or anesthesia.

First claim

What is claimed is:

1. A compound of the Formula (II):

wherein:
R a a is hydrogen, chloro, fluoro, hydroxy, alkyl, methoxy, substituted ethoxy, C 3 -C 6 alkoxy, —C(O)R a , —C(O)N(R b )(R c ), —C(O)OR a , —N(R f )(R g ), —OC(O)N(R b )(R c ), —OC(O)OR a , —OC(O)R a , —S(O) 0-2 R a , —S(O) 0-2 OR a , or —S(O) 0-2 N(R b )(R c );
R 2b is hydrogen, halo, hydroxy, alkyl, methoxy, substituted ethoxy, C 3 -C 6 alkoxy, —C(O)R a , —C(O)N(R b )(R c ), —C(O)OR a , —N(R f )(R g ), —OC(O)N(R b )(R c ), —OC(O)OR a , —OC(O)R a , —S(O) 0-2 R a , —S(O) 0-2 OR a , or —S(O) 0-2 N(R b )(R c );
wherein one of R 2a and R 2b is hydrogen;
each R a is hydrogen or C 1 -C 6 alkyl;
each R b and R c is independently hydrogen or C 1 -C 6 alkyl, or
R b and R c , taken together with the nitrogen atom to which they are attached, form a 3-7-membered heterocyclic ring; and
each R f and R g is independently hydrogen or C i -C 6 alkyl, or
R f and R g , taken together with the nitrogen atom to which they are attached, form a 3-7-membered heterocyclic ring optionally comprising one additional heteroatom selected from nitrogen and sulfur.

2. The compound of claim 1 , wherein the compound is a compound of the Formula (IIb):

wherein:
R 2a a is hydrogen, chloro, fluoro, hydroxy, alkyl, methoxy, substituted ethoxy, C 3 -C 6 alkoxy, —C(O)R a , —C(O)N(R b )(R c ), —C(O)OR a , —N(R f )(R g ), —OC(O)N(R b )(R c ), —OC(O)OR a , —OC(O)R a , —S(O) 0-2 R a , —S(O) 0-2 OR a , or —S(O) 0-2 N(R b ) c );
R 2b is hydrogen, halo, hydroxy, alkyl, methoxy, substituted ethoxy, C 3 -C 6 alkoxy, —C(O)R a , —C(O)N(R b )(R c ), —C(O)OR a , —N(R f )(R g ) , —OC(O)N(R b )(R c ), —OC(O)OR a , —OC(O)R a , —S(O) 0-2 R a , —S(O) 0-2 OR a , or —S(O) 0-2 N(R b ) c );
wherein one of R 2a and R 2b is hydrogen;
each R a is hydrogen or C 1 -C 6 alkyl;
each R b and R c is independently hydrogen or C 1 -C 6 alkyl, or
R b and R c , taken together with the nitrogen atom to which they are attached, form a 3-7-membered heterocyclic ring; and
each R f and R g is independently hydrogen or C 1 -C 6 alkyl, or
R f and R g , taken together with the nitrogen atom to which they are attached, form a 3-7-membered heterocyclic ring optionally comprising one additional heteroatom selected from nitrogen and sulfur.

3. The compound of claim 1 , wherein R 2a or R 2b is is alkyl, methoxy, substituted ethoxy, or C 3 -C 6 alkoxy.

4. The compound of claim 3 , wherein R 2a a is alkyl, methoxy, substituted ethoxy, or C 3 -C 6 alkoxy.

5. The compound of claim 2 , wherein R 2b is hydrogen.

6. The compound of claim 1 , wherein the compound is selected from:

7. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable excipient.

Assignees

• Sage Therapeutics Inc

Inventors

• Martinez Botella Gabriel
• Harrison Boyd L
• Robichaud Albert J
• Salituro Francesco G

Classifications

• A61P43/00

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

• A61P25/20

  Hypnotics; Sedatives · CPC title

• A61P25/08

  Antiepileptics; Anticonvulsants · CPC title

• A61P23/00

  Anaesthetics · CPC title

• A61P21/02

  Muscle relaxants, e.g. for tetanus or cramps · CPC title