US 12,351,569 B2
ALDH-2 inhibitor compounds and methods of use
Brent Blackburn, Los Altos, CA (US)
Assigned to Amygdala Neurosciences, Inc., San Francisco, CA (US)
Filed by Amygdala Neurosciences, Inc., San Francisco, CA (US)
Filed on Jun. 13, 2023, as Appl. No. 18/209,119.
Claims priority of provisional application 63/351,997, filed on Jun. 14, 2022.
Prior Publication US 2023/0399307 A1, Dec. 14, 2023
Int. Cl. C07D 401/04 (2006.01); A61K 9/00 (2006.01); A61K 9/20 (2006.01); A61K 9/48 (2006.01); A61K 47/06 (2006.01); A61K 47/12 (2006.01); A61K 47/14 (2017.01); A61K 47/26 (2006.01); A61K 47/36 (2006.01); A61K 47/38 (2006.01); A61K 47/44 (2017.01); C07D 401/14 (2006.01); C07D 403/04 (2006.01)
CPC C07D 401/04 (2013.01) [A61K 9/0014 (2013.01); A61K 9/2009 (2013.01); A61K 9/2013 (2013.01); A61K 9/2027 (2013.01); A61K 9/2054 (2013.01); A61K 9/4825 (2013.01); A61K 9/4858 (2013.01); A61K 9/4866 (2013.01); A61K 47/06 (2013.01); A61K 47/12 (2013.01); A61K 47/14 (2013.01); A61K 47/26 (2013.01); A61K 47/36 (2013.01); A61K 47/38 (2013.01); A61K 47/44 (2013.01); C07D 401/14 (2013.01); C07D 403/04 (2013.01)] 26 Claims
 
1. A compound of structural Formula (I):

OG Complex Work Unit Chemistry
wherein:
X1 is N or CR3, X2 is N or CR4, X3 is N or CR6, with the proviso that no more than one of X1, X2, and X3 is N;
R10 is H, optionally substituted C1-6 alkyl, —CH2OH, —CH2OP(O)(OR20)(OR21);
R11 is H, halogen, optionally substituted C1-6 alkyl, or cycloalkyl;
R7 is H, or optionally substituted C1-6 alkyl;
each of R2, R3, R4, R5, R6, R8, and R9, is independently H, halogen, —CF3, —OH, —CH2OH, —CN, optionally substituted alkyl, optionally substituted alkylene, optionally substituted alkynyl, optionally substituted alkoxy, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heteroaralkyl, optionally substituted heterocyclyl, aminocarbonyl, acyl, acylamino, —O—(C1 to C6-alkyl)-O—(C1 to C6-alkyl), —CH2OP(O)(OR20)(OR21), —SO2NR24R25; or —NR24R25;
each of R20 and R21 is independently Na+, Li+, K+, hydrogen, C1-6 alkyl; or R20 and R21 can be combined to represent a single divalent cation Zn2+, Ca2+, or Mg2+; and
each of R24 and R25 is independently chosen from hydrogen or C1-6 alkyl or when combined together with the nitrogen to which they are attached form a heterocycle;
or a pharmaceutically acceptable salt, ester, single stereoisomer, mixture of stereoisomers, or a tautomer thereof.