US 11,939,302 B2
Compounds for the treatment of Alzheimer's disease
James A. Nieman, Sherwood Park (CA); Jack Jhamandas, Edmonton (CA); Bing Bai, Edmonton (CA); Alexandr Belovodskiy, Edmonton (CA); Wen Fu, Edmonton (CA); Mostofa Hena, Edmonton (CA); Michael Houghton, Danville, CA (US); Appan Srinivas Kandadai, Edmonton (CA); Ryoichi Kimura, Sanyo-Onoda (JP); Kamlesh Kumar Sahu, Edmonton (CA); and D. Lorne Tyrrell, Edmonton (CA)
Assigned to The Governors of the University of Alberta, Edmonton (CA)
Filed by The Governors of the University of Alberta, Edmonton (CA)
Filed on Oct. 19, 2021, as Appl. No. 17/505,250.
Claims priority of provisional application 63/094,777, filed on Oct. 21, 2020.
Prior Publication US 2022/0119356 A1, Apr. 21, 2022
Int. Cl. A61K 31/55 (2006.01); A61P 25/28 (2006.01); C07D 241/44 (2006.01); C07D 243/12 (2006.01); C07D 243/14 (2006.01); C07D 403/12 (2006.01)
CPC C07D 243/12 (2013.01) [A61P 25/28 (2018.01); C07D 241/44 (2013.01); C07D 243/14 (2013.01); C07D 403/12 (2013.01)] 20 Claims
 
1. A method of treating Alzheimer's disease, the method comprising:
administering to a subject in need thereof, a therapeutically effective amount of a compound of formula (I):

OG Complex Work Unit Chemistry
wherein:
R is selected from the group consisting of —H, C1-C6-alkyl, and substituted C1-C6-alkyl;
each R1 is independently selected from the group consisting of H, halogen, C1-C6-alkyl, substituted C1-C6-alkyl, C3-C6-cycloalkyl, substituted C3-C6-cycloalkyl, —OR2, heterocyclyl, substituted heterocyclyl, aryl, substituted aryl, heteroaryl, and substituted heteroaryl;
each R2 is independently selected from the group consisting of —H, C1-C6-alkyl, and substituted C1-C6-alkyl;
each W is selected from the group consisting of —CH2—, —CHR3— and —CR3R4—;
R3 and R4 are independently selected from the group consisting of halogen, C1-C6-alkyl, substituted C1-C6-alkyl, C3-C6-cycloalkyl, substituted C3-C6-cycloalkyl, heterocyclyl, substituted heterocyclyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, fused-heterocycle, and substituted fused-heterocycle, or together R3 and R4 comprise a carbocycle, substituted carbocycle or oxo;
m is selected from 1, 2 or 3;
Q is —C(═O)—;
X is absent;
Y is selected from the group consisting of —CH2—, and —C(═O)—;
Z is selected from the group consisting of —OR5, halogen, —CN, —NR5R5, —NHC(═O)R5, —NHC(═O)NR5R5, aryl, and heteroaryl; and
each R5 is independently selected from the group consisting of —H, C1-C6-alkyl, substituted C1-C6-alkyl, aryl, substituted aryl, heteroaryl, and substituted heteroaryl;
or an enantiomer, a mixture of enantiomers, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof;
or a pharmaceutically acceptable salt, solvate, or hydrate thereof.