US 12,065,407 B2
Dual acting FKBP12 and FKBP52 inhibitors
Surya Kanta De, San Diego, CA (US); Sridhar G. Prasad, San Diego, CA (US); and Marshall C. Peterman, Oceanside, CA (US)
Assigned to PLEX PHARMACEUTICALS, INC., San Diego, CA (US)
Appl. No. 16/640,919
Filed by PLEX PHARMACEUTICALS, INC., San Diego, CA (US)
PCT Filed Aug. 21, 2018, PCT No. PCT/US2018/047274
§ 371(c)(1), (2) Date Feb. 21, 2020,
PCT Pub. No. WO2019/040463, PCT Pub. Date Feb. 28, 2019.
Claims priority of provisional application 62/547,976, filed on Aug. 21, 2017.
Claims priority of provisional application 62/547,977, filed on Aug. 21, 2017.
Prior Publication US 2020/0399219 A1, Dec. 24, 2020
Int. Cl. C07D 213/30 (2006.01); A61K 31/4184 (2006.01); A61K 47/30 (2006.01); C07C 237/22 (2006.01); C07D 209/42 (2006.01); C07D 231/56 (2006.01); C07D 235/08 (2006.01); C07D 235/10 (2006.01); C07D 235/14 (2006.01); C07D 235/30 (2006.01); A61K 9/00 (2006.01)
CPC C07D 213/30 (2013.01) [A61K 47/30 (2013.01); C07C 237/22 (2013.01); C07D 209/42 (2013.01); C07D 231/56 (2013.01); C07D 235/10 (2013.01); C07D 235/14 (2013.01); C07D 235/30 (2013.01); A61K 9/0043 (2013.01)] 9 Claims
 
1. A pharmaceutical composition comprising a compound or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, wherein the compound is of Formula (II):

OG Complex Work Unit Chemistry
wherein R1 is selected from hydrogen; halogen; nitro; cyano; amino; hydroxy; carboxy; (C1-C6)alky; halo(C1-C6)alkyl; (C1-C6)alkoxy; halo(C1-C6)alkoxy; (C3-C10)cycloalkyl; halo(C3-C10)cycloalkyl; (C3-C10)cycloalkylthio; halo(C3-C10)cycloalkythio; (C3-C10)heterocycloalkyl; halo(C3-C10)heterocycloalky; (C1-C6)alkylamino; di(C1-C6)alkylamino; (C1-C6)alkylthio; halo(C1-C6)alkylthio; (C1-C6)alkylsulfinyl; halo(C1-C6)alkylsulfinyl; (C1-C6)alkylsulfonyl; halo(C1-C6)alkylsulfonyl; (C3-C10)cycloalkylsulfinyl; halo(C3-C10)cycloalkylsulfinyl; (C3-C10)cycloalkylsulfonyl; halo(C3-C10)cycloalkylsulfonyl; aryl, heteroaryl, arylamine, or heterocyclyl, optionally substituted with halogen, nitro, cyano, amino, hydroxy, carboxy, (C1-C6)alkyl, halo(C1-C6)alkyl, (C1-C6)alkoxy, or halo(C1-C6)alkoxy; and an aryl ring fused to the relevant phenyl ring, either ring being optionally substituted with halogen, nitro, cyano, amino, hydroxy, carboxy, (C1-C6)alkyl, halo(C1-C6)alkyl, (C1-C6)alkoxy, halo(C1-C6)alkoxy or arylamine;
R3 is selected from halogen; nitro; cyano; amino; hydroxy; carboxy; (C1-C6)alkyl; halo(C1-C6)alkyl; (C1-C6)alkoxy; halo(C1-C6)alkoxy; (C3-C10)cycloalkyl; halo(C3-C10)cycloalkyl; (C3-C10)cycloalkylthio; halo(C3-C10)cycloalkylthio; (C3-C10)heterocycloalkyl; halo(C3-C10)heterocycloalkyl; (C1-C6)alkylamino; di(C1-C6)alkylamino; (C1-C6)alkylthio; halo(C1-C6)alkylthio; (C1-C6)alkylsulfinyl; halo(C1-C6)alkylsulfinyl; (C1-C6)alkylsulfonyl; halo(C1-C6)alkylsulfonyl; (C3-C10)cycloalkylsulfinyl; halo(C3-C10)cycloalkylsulfinyl; (C3-C10)cycloalkylsulfonyl; halo(C3-C10)cycloalkylsulfonyl; aryl, heteroaryl, arylamine, or heterocyclyl, optionally substituted with halogen, nitro, cyano, amino, hydroxy, carboxy, (C1-C6)alkyl, halo(C1-C6)alkyl, (C1-C6)alkoxy, or halo(C1-C6)alkoxy; and an aryl ring fused to the relevant phenyl ring, either ring being optionally substituted with halogen, nitro, cyano, amino, hydroxy, carboxy, (C1-C6)alkyl, halo(C1-C6)alkyl, (C1-C6)alkoxy, halo(C1-C6)alkoxy or arylamine;
X—Y is CH═CH, C≡C, or N═N;
R2 is selected from (C1-C6)alkyl; halo(C1-C6)alkyl; (C2-C6)alkenyl; halo(C2-C6)alkenyl;
(C2-C6)alkynyl; halo(C2-C6)alkynyl; (C3-C10)cycloalkyl; halo(C3-C10)cycloalkyl; heterocyclyl, aryl, or heteroaryl, each optionally substituted with one or more groups independently selected from halogen, nitro, cyano, amino, hydroxy, carboxy, (C1-C6)alkyl, halo(C1-C6)alkyl, (C1-C6)alkoxy, or halo(C1-C6)alkoxy; and
m is 0 to 4.
 
7. A compound of Formula (II):

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof,
wherein R1 is selected from hydrogen; halogen; nitro; cyano; amino; hydroxy; carboxy; (C1-C6)alky; halo(C1-C6)alkyl; (C1-C6)alkoxy; halo(C1-C6)alkoxy; (C3-C10)cycloalkyl; halo(C3-C10)cycloalkyl; (C3-C10)cycloalkylthio; halo(C3-C10)cycloalkythio; (C3-C10)heterocycloalkyl; halo(C3-C10)heterocycloalky; (C1-C6)alkylamino; di(C1-C6)alkylamino; (C1-C6)alkylthio; halo(C1-C6)alkylthio; (C1-C6)alkylsulfinyl; halo(C1-C6)alkylsulfinyl; (C1-C6)alkylsulfonyl; halo(C1-C6)alkylsulfonyl; (C3-C10)cycloalkylsulfinyl; halo(C3-C10)cycloalkylsulfinyl; (C3-C10)cycloalkylsulfonyl; halo(C3-C10)cycloalkylsulfonyl; aryl, heteroaryl, arylamine, or heterocyclyl, optionally substituted with halogen, nitro, cyano, amino, hydroxy, carboxy, (C1-C6)alkyl, halo(C1-C6)alkyl, (C1-C6)alkoxy, or halo(C1-C6)alkoxy; and an aryl ring fused to the relevant phenyl ring, either ring being optionally substituted with halogen, nitro, cyano, amino, hydroxy, carboxy, (C1-C6)alkyl, halo(C1-C6)alkyl, (C1-C6)alkoxy, halo(C1-C6)alkoxy or arylamine;
R3 is selected from halogen; nitro; cyano; amino; hydroxy; carboxy; (C1-C6)alkyl; halo(C1-C6)alkyl; (C1-C6)alkoxy; halo(C1-C6)alkoxy; (C3-C10)cycloalkyl; halo(C3-C10)cycloalkyl; (C3-C10)cycloalkylthio; halo(C3-C10)cycloalkylthio; (C3-C10)heterocycloalkyl; halo(C3-C10)heterocycloalkyl; (C1-C6)alkylamino; di(C1-C6)alkylamino; (C1-C6)alkylthio; halo(C1-C6)alkylthio; (C1-C6)alkylsulfinyl; halo(C1-C6)alkylsulfinyl; (C1-C6)alkylsulfonyl; halo(C1-C6)alkylsulfonyl; (C3-C10)cycloalkylsulfinyl; halo(C3-C10)cycloalkylsulfinyl; (C3-C10)cycloalkylsulfonyl; halo(C3-C10)cycloalkylsulfonyl; aryl, heteroaryl, arylamine, or heterocyclyl, optionally substituted with halogen, nitro, cyano, amino, hydroxy, carboxy, (C1-C6)alkyl, halo(C1-C6)alkyl, (C1-C6)alkoxy, or halo(C1-C6)alkoxy; and an aryl ring fused to the relevant phenyl ring, either ring being optionally substituted with halogen, nitro, cyano, amino, hydroxy, carboxy, (C1-C6)alkyl, halo(C1-C6)alkyl, (C1-C6)alkoxy, halo(C1-C6)alkoxy or arylamine;
X—Y is C≡C;
R2 is a (C2-C6)alkenyl or a (C2-C6)alkynyl; and
m is 1.