US 12,129,276 B2
Oxysterols and methods of use 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, INC., Cambridge, MA (US)
Filed by SAGE THERAPEUTICS, INC., Cambridge, MA (US)
Filed on Mar. 2, 2023, as Appl. No. 18/116,557.
Application 18/116,557 is a continuation of application No. 16/902,730, filed on Jun. 16, 2020, abandoned.
Application 16/902,730 is a continuation of application No. 16/028,790, filed on Jul. 6, 2018, granted, now 10,723,758, issued on Jul. 28, 2020.
Application 16/028,790 is a continuation of application No. 15/319,504, granted, now 10,259,840, issued on Apr. 16, 2019, previously published as PCT/US2015/036510, filed on Jun. 18, 2015.
Claims priority of provisional application 62/107,236, filed on Jan. 23, 2015.
Claims priority of provisional application 62/014,014, filed on Jun. 18, 2014.
Prior Publication US 2023/0348526 A1, Nov. 2, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. C07J 9/00 (2006.01); A61K 9/00 (2006.01); A61K 9/20 (2006.01); A61K 9/48 (2006.01); A61K 31/575 (2006.01); C07J 13/00 (2006.01); C07J 31/00 (2006.01)
CPC C07J 9/00 (2013.01) [A61K 9/0019 (2013.01); A61K 9/0095 (2013.01); A61K 9/2063 (2013.01); A61K 9/4866 (2013.01); A61K 31/575 (2013.01); C07J 9/005 (2013.01); C07J 13/005 (2013.01); C07J 13/007 (2013.01); C07J 31/006 (2013.01)] 20 Claims
 
1. A compound of Formula (I):

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof;
wherein:
R1 is hydrogen, 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 3-7 membered ring;
each of R4a and R4b is independently absent, hydrogen, C1-C6 alkyl, or halo;
X is —C(RX)2— or —O—, wherein RX is independently hydrogen, halo, or one RX group and R5b are joined to form a double bond;
Y is —ORY, wherein RY is hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, —C(O)RA, —C(O)ORA, —C(O)NRBRC, or —S(O)2RD;
each instance of R5a and R5b is independently hydrogen, halo, or C1-C6 alkyl;
each of R6a and R6b is independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, carbocyclyl, heterocyclyl, aryl, or heteroaryl, or
R6a and R6b, taken together with the carbon atom to which they are attached, form a 3-6 membered ring; or
R5a and R6a, together with the carbon atoms to which they are attached, form a 3-6-membered ring; and
R7 is absent or hydrogen in the alpha configuration;
R8 is hydrogen, halo, C1-6alkyl, 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 —CR7 and —CR4aR4b is a double bond, then one of R4a or R4b is absent; and
when one of the custom character is a double bond, R7 is absent;
RA is hydrogen, C1-C6 alkyl, carbocyclyl, heterocyclyl, aryl, or heteroaryl;
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 3-7-membered ring; and
RD is hydrogen, C1-C6 alkyl, carbocyclyl, heterocyclyl, aryl, or heteroaryl.