Neuroactive steroids, compositions, and uses thereof
View Patent ↗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.
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.