US 12,473,327 B2
Neuroactive steroids, compositions and uses thereof
Boyd L. Harrison, Princeton Junction, NJ (US); Gabriel Martinez Botella, Wayland, MA (US); Albert Jean Robichaud, Boston, MA (US); and Francesco G. Salituro, Marlborough, MA (US)
Assigned to Sage Therapeutics, LLP, Rockville, MD (US)
Filed by Sage Therapeutics, Inc., Cambridge, MA (US)
Filed on Aug. 24, 2023, as Appl. No. 18/455,007.
Application 18/455,007 is a division of application No. 17/472,744, filed on Sep. 13, 2021, granted, now 11,780,875.
Application 17/472,744 is a division of application No. 16/924,814, filed on Jul. 9, 2020, granted, now 11,149,057, issued on Oct. 19, 2021.
Application 16/924,814 is a division of application No. 16/269,779, filed on Feb. 7, 2019, granted, now 10,745,436, issued on Aug. 18, 2020.
Application 16/269,779 is a division of application No. 15/319,503, granted, now 10,246,482, issued on Apr. 2, 2019, previously published as PCT/US2015/036500, filed on Jun. 18, 2015.
Claims priority of provisional application 62/014,010, filed on Jun. 18, 2014.
Prior Publication US 2023/0391816 A1, Dec. 7, 2023
Int. Cl. C07J 41/00 (2006.01); C07J 1/00 (2006.01); C07J 5/00 (2006.01); C07J 7/00 (2006.01); C07J 13/00 (2006.01); C07J 17/00 (2006.01); C07J 21/00 (2006.01)
CPC C07J 41/005 (2013.01) [C07J 5/0015 (2013.01); C07J 7/002 (2013.01); C07J 7/009 (2013.01); C07J 17/00 (2013.01); C07J 1/0011 (2013.01); C07J 7/007 (2013.01); C07J 7/0085 (2013.01); C07J 13/007 (2013.01); C07J 21/00 (2013.01); C07J 21/006 (2013.01); C07J 21/008 (2013.01)] 16 Claims
 
1. A method for treating a CNS-related disorder, wherein the CNS-related disorder is a traumatic brain injury in a human subject in need thereof comprising administering to the human subject a therapeutically effective amount of a) a compound of Formula (I) or a pharmaceutically acceptable salt thereof or b) a pharmaceutical composition comprising a compound of Formula (I) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient, wherein:

OG Complex Work Unit Chemistry
R1 is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, carbocyclyl, or heterocyclyl;
each of R2a and R2b is independently hydrogen, C1-C6 alkyl, halo, cyano, —ORA, or —NRBRC, or
R2a and R2b together with the carbon atom to which they are attached form a ring;
R3 is hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, —C(O)RA, —C(O)ORA, or —C(O) NRBRC;
R4 is hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, carbocyclyl, or —ORA,
custom character represents a single or double bond, wherein when one custom character is a double bond, the other custom character is a single bond;
wherein when the custom character between CR6 and CR5aR5b is a double bond, then one of R5a or R5b is absent; and
when one of the custom character is a double bond, R6 is absent;
each of R5a and R5b is independently absent, hydrogen, C1-C6 alkyl, or halo;
R6 is absent or hydrogen;
Z is —CR7aR7b—, wherein each of R7a and R7b is independently hydrogen or C1-C6 alkyl, or R7a and R7b, together with the carbon atom to which they are attached, form a ring;
RA is hydrogen, C1-C6 alkyl, carbocyclyl, heterocyclyl, aryl, or heteroaryl; and
each of RB and RC is independently hydrogen, C1-C6 alkyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, or taken together with the atom to which they are attached form a ring.