US2016229887A1PendingUtilityA1
Neuroactive steroids, compositions, and uses thereof
Est. expiryAug 23, 2033(~7.1 yrs left)· nominal 20-yr term from priority
Inventors:Gabriel Martinez BotellaBoyd L. HarrisonAlbert Jean RobichaudFrancesco G. SalituroRobert Jason HerrRobert Borbo Kargbo
A61P 9/00A61P 25/18A61P 29/02A61P 25/24A61P 25/28A61P 25/30A61P 25/04A61P 27/16A61P 25/08A61P 25/36A61P 25/20A61P 25/00A61P 23/00C07J 21/00A61K 45/06A61K 31/58C07J 43/003C07J 13/007C07J 7/007C07J 21/008C07J 7/002C07J 7/0085C07J 1/0059
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Claims
Abstract
Described herein are neuroactive steroids of the Formula (I): or a pharmaceutically acceptable salt thereof; wherein -------, R 1 , R 2 , R 5 , A and L 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.
Claims
exact text as granted — not AI-modified1 . A compound of the Formula (I):
a pharmaceutically acceptable salt thereof,
wherein:
A is an optionally substituted nitrogen-containing heteroaryl or heterocyclyl;
L is —C(R 3 )(R 3 )—, —O—, —S—, or —NR 3 —;
R 1 is hydrogen or C 1 -C 6 alkyl, C 1 -C 6 alkenyl, C 1 -C 6 alkynyl, carbocyclyl, or heterocyclyl;
R 2 is hydrogen, C 1 -C 6 alkyl (e.g., C 1 -C 6 haloalkyl), or C 1 -C 6 alkoxy;
each R 3 is independently hydrogen or C 1 -C 6 alkyl;
R 5 is absent or hydrogen; and
represents a single or double bond, wherein
when one of is a double bond, the other is a single bond; and
when one of the is a double bond, R 5 is absent.
2 - 13 . (canceled)
14 . The compound of claim 13 , wherein the compound is of the Formula (Ia-3):
wherein
R 4 is cyano, nitro, hydroxy, halo, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, —C(O)R a , —C(O)N(R b )(R c ), —C(O)OR a , —N(R b )(R c ), —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 );
each R a is hydrogen or C 1 -C 6 alkyl;
each R b and R c is independently hydrogen, C 1 -C 6 alkyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, or
R b and R c , together with the nitrogen atom to which they are bound to form a ring (e.g., a 3-7-membered ring, e.g., a 5-7-membered ring; a ring containing at least one heteroatom, e.g., a nitrogen, oxygen, or sulfur atom); and
n is 0, 1, 2, or 3.
15 . (canceled)
16 . The compound of claim 14 , wherein n is 0.
17 - 22 . (canceled)
23 . The compound of claim 14 , wherein R 1 is C 1 -C 6 alkyl.
24 - 25 . (canceled)
26 . The compound of claim 14 , wherein the compound is selected from:
27 . A compound of the Formula (Ib):
a pharmaceutically acceptable salt thereof,
wherein:
A is an optionally substituted nitrogen-containing heteroaryl or heterocyclyl;
L is —C(R 3 )(R 3 )—, —O—, —S—, or —NR 3 —;
R 1 is hydrogen or C 1 -C 6 alkyl, C 1 -C 6 alkenyl, C 1 -C 6 alkynyl, carbocyclyl, or heterocyclyl;
R 2 is C 1 -C 6 alkyl (e.g., C 1 -C 6 haloalkyl) or C 1 -C 6 alkoxy;
each R 3 is independently hydrogen or C 1 -C 6 alkyl;
R 5 is absent or hydrogen; and
represents a single or double bond, wherein
when one of is a double bond, the other is a single bond; and
when one of the is a double bond, R 5 is absent.
28 - 29 . (canceled)
30 . The compound of claim 27 , wherein the compound is of the Formula (Ib-3)
wherein
R 4 is cyano, nitro, hydroxy, halo, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, —C(O)R a , —C(O)N(R b )(R c ), —C(O)OR a , —N(R b )(R c ), —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 );
each R a is hydrogen or C 1 -C 6 alkyl;
each R b and R c is independently hydrogen, C 1 -C 6 alkyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, or
R b and R c , together with the nitrogen atom to which they are bound to form a ring (e.g., a 3-7-membered ring, e.g., a 5-7-membered ring; a ring containing at least one heteroatom, e.g., a nitrogen, oxygen, or sulfur atom); and
n is 0, 1, 2, or 3.
31 . The compound of claim 27 , wherein the compound is of the Formula (Ib-4)
wherein
R 4 is cyano, nitro, hydroxy, halo, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, —C(O)R a , —C(O)N(R b )(R c ), —C(O)OR a , —N(R b )(R c ), —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 );
each R a is hydrogen or C 1 -C 6 alkyl;
each R b and R c is independently hydrogen, C 1 -C 6 alkyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, or
R b and R c , together with the nitrogen atom to which they are bound to form a ring (e.g., a 3-7-membered ring, e.g., a 5-7-membered ring; a ring containing at least one heteroatom, e.g., a nitrogen, oxygen, or sulfur atom); and
n is 0, 1, 2, or 3.
32 . The compound of claim 27 , wherein A is monocyclic.
33 . The compound of claim 27 , wherein A is bicyclic.
34 - 36 . (canceled)
37 . The compound of claim 27 , wherein A is a 5-membered or 6-membered heteroaryl or heterocyclyl comprising 1, 2, 3, or 4 nitrogen atoms.
38 . (canceled)
39 . The compound of claim 37 , wherein A is morpholine or piperazine.
40 - 41 . (canceled)
42 . The compound of claim 27 , wherein the heteroaryl is benzotriazole, azabenzotriazole, diazabenzotriazole, benzopyrazole, azabenzopyrazole, or diazabenzopyrazole.
43 - 45 . (canceled)
46 . The compound of claim 37 , wherein A is pyrazole, triazole, or tetrazole.
47 . The compound of claim 27 , wherein R 1 is C 1 -C 6 alkyl, C 1 -C 6 alkenyl, C 1 -C 6 alkynyl, carbocyclyl, or heterocyclyl.
48 . (canceled)
49 . The compound of claim 47 , wherein R 1 is methyl, ethyl, or isopropyl.
50 . (canceled)
51 . The compound of claim 27 , wherein R 2 is methyl.
52 . The compound of claim 27 , wherein n is 0.
53 . The compound of claim 27 , wherein n is 1 or 2, and R 4 is cyano, halo, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, —C(O)R a , or —S(O) 0-2 R a .
54 - 59 . (canceled)
60 . The compound of claim 53 , wherein R a is C 1 -C 6 alkyl.
61 . The compound of claim 60 , wherein R a is methyl.
62 . The compound of claim 53 , wherein R 4 is —S(O) 2 R a .
63 . The compound of claim 62 , wherein R a is methyl.
64 . The compound of claim 27 , wherein R 1 is C 1 -C 6 alkyl and R 4 is —C(O)R a .
65 . (canceled)
66 . The compound of claim 27 , wherein n is 0 or 1; R 1 is hydrogen or C 1 -C 6 alkyl; and R 2 is methyl.
67 . The compound of claim 27 , wherein R 1 is methyl, ethyl, or isopropyl.
68 . (canceled)
69 . The compound of claim 27 , wherein R 4 is C 1 -C 6 alkyl, —C(O)R a , or —S(O) 0-2 R a .
70 - 72 . (canceled)
73 . The compound of claim 27 , wherein the compound is selected from:
74 . A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable excipient.
75 - 90 . (canceled)Join the waitlist — get patent alerts
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