US 11,731,966 B2
Compounds and their methods of use
Kiran Reddy, Boston, MA (US); Andrew Mark Griffin, L'lle Bizard (CA); Brian Edward Marron, Durham, NC (US); and Gabriel Martinez Botella, Wayland, MA (US)
Assigned to PRAXIS PRECISION MEDICINES, INC., Boston, MA (US)
Appl. No. 16/500,795
Filed by Praxis Precision Medicines, Inc., Cambridge, MA (US)
PCT Filed Apr. 4, 2018, PCT No. PCT/US2018/026099
§ 371(c)(1), (2) Date Oct. 3, 2019,
PCT Pub. No. WO2018/187480, PCT Pub. Date Oct. 11, 2018.
Claims priority of provisional application 62/481,463, filed on Apr. 4, 2017.
Prior Publication US 2021/0355118 A1, Nov. 18, 2021
Int. Cl. C07D 471/04 (2006.01); C07D 249/18 (2006.01); C07D 487/04 (2006.01); C07D 401/04 (2006.01); C07D 413/06 (2006.01)
CPC C07D 471/04 (2013.01) [C07D 249/18 (2013.01); C07D 401/04 (2013.01); C07D 413/06 (2013.01); C07D 487/04 (2013.01)] 14 Claims
 
1. A compound of Formula (II), (III) or (IV), wherein the compound of Formula (II) is:

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof, wherein:
each of X, Y, and Z is independently N or CR2;
R1 is independently alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, or heteroaryl, wherein alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, and heteroaryl are optionally substituted with one or more R4;
R2 is hydrogen, alkyl or halogen;
each R3 is independently alkyl, halo, cyano, nitro, carbocyclyl, heterocyclyl, —ORc, —N(Rd)2, —C(O)Rc, —C(O)ORc, or —C(O)N(Rd)2, wherein alkyl, carbocyclyl, and heterocyclyl are optionally substituted with one or more R5;
each R4 and R5 is independently alkyl, halo, cyano, nitro, 5 or 6-membered heteroaryl, or —ORc, wherein the 5 or 6 membered heteroaryl is optionally substituted with alkyl;
each Rc is independently hydrogen, alkyl, aryl, carbocyclyl, or heteroaryl, wherein alkyl, aryl, carbocyclyl, and heteroaryl is optionally substituted by one or more R6;
each Rd is independently hydrogen or alkyl;
each R6 is independently alkyl, carbocyclyl, heterocyclyl, halo, cyano, nitro, or —OH, and
n is 0, 1, 2, or 3;
wherein the compound is not a compound selected from the group consisting of:

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof;
wherein the compound of Formula (III) is:

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof, wherein:
each of X, Y, and Z is independently N or CR2;
R1 is independently hydrogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, or heteroaryl, wherein alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl are optionally substituted with one or more R4;
R2 is hydrogen, alkyl or halogen;
R7 is carbocyclyl optionally substituted with one or more R5;
each R3 is independently alkyl, halo, cyano, nitro, carbocyclyl, heterocyclyl, —ORc, —N(Rd)2, —C(O)Rc, —C(O)ORc, or —C(O)N(Rd)2, wherein alkyl, carbocyclyl, and heterocyclyl are optionally substituted with one or more R5;
each R4 and R5 is independently alkyl, halo, cyano, nitro, 5 or 6-membered heteroaryl, or —ORc, wherein the 5 or 6 membered heteroaryl is optionally substituted with alkyl;
each Rc is independently hydrogen, alkyl, aryl, carbocyclyl, or heteroaryl, wherein alkyl, aryl, carbocyclyl, and heteroaryl is optionally substituted by one or more R6;
each Rd is independently hydrogen or alkyl;
each R6 is independently alkyl, carbocyclyl, heterocyclyl, halo, cyano, nitro, or —OH, and
n is 0, 1, 2, or 3; or
wherein the compound of Formula (IV) is:

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof, wherein:
each of X, Y, and Z is independently N or CR2;
R1 is independently hydrogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, or heteroaryl, wherein alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl are optionally substituted with one or more R4;
R2 is hydrogen, alkyl or halogen;
each R3 is independently alkyl, halo, cyano, nitro, carbocyclyl, heterocyclyl, —ORc, —N(Rd)2, —C(O)Rc, —C(O)ORc, or —C(O)N(Rd)2, wherein alkyl, carbocyclyl, and heterocyclyl are optionally substituted with one or more R5;
each R4 and R5 is independently alkyl, halo, cyano, nitro, 5 or 6-membered heteroaryl, or —ORc, wherein the 5 or 6 membered heteroaryl is optionally substituted with alkyl;
each Rc is independently hydrogen, alkyl, aryl, carbocyclyl, or heteroaryl, wherein alkyl, aryl, carbocyclyl, and heteroaryl is optionally substituted by one or more R6;
each Rd is independently hydrogen or alkyl;
each R6 is independently alkyl, carbocyclyl, heterocyclyl, halo, cyano, nitro, or —OH, and
n is 0, 1, 2, or 3;
wherein the compound is not a compound selected from the group consisting of:

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof.