US 11,725,001 B2
Bicyclic compound and use thereof
Yong Je Shin, Gyeonggi-do (KR); Jin Hee Kim, Gyeonggi-do (KR); Jun Lee, Gyeonggi-do (KR); Sook Kyung Park, Gyeonggi-do (KR); Ho Yeon Lee, Gyeonggi-do (KR); Hyun Suk Choi, Gyeonggi-do (KR); Se Hyuk Kim, Gyeonggi-do (KR); Eun Ji Kang, Gyeonggi-do (KR); Ho Youl Lee, Gyeonggi-do (KR); and Soo Yeon Jung, Gyeonggi-do (KR)
Assigned to SK BIOPHARMACEUTICALS CO., LTD., Gyeonggi-do (KR)
Filed by SK BIOPHARMACEUTICALS CO., LTD., Gyeonggi-do (KR)
Filed on Jul. 19, 2021, as Appl. No. 17/378,957.
Application 17/378,957 is a continuation of application No. 17/102,871, filed on Nov. 24, 2020, granted, now 11,111,237.
Application 17/102,871 is a continuation of application No. PCT/KR2020/013424, filed on Sep. 29, 2020.
Claims priority of application No. 10-2019-0122177 (KR), filed on Oct. 2, 2019.
Prior Publication US 2022/0402902 A1, Dec. 22, 2022
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 413/06 (2006.01); C07D 413/14 (2006.01); C07D 491/08 (2006.01); C07D 491/107 (2006.01); C07D 401/06 (2006.01)
CPC C07D 413/06 (2013.01) [C07D 401/06 (2013.01); C07D 413/14 (2013.01); C07D 491/08 (2013.01); C07D 491/107 (2013.01)] 20 Claims
 
1. A method for treating a disease associated with protein arginine methyltransferase 5 (PRMT5) inhibition, comprising:
administering to a subject in need thereof a therapeutically effective amount of the compound of Formula 1 or a pharmaceutically acceptable salt thereof:

OG Complex Work Unit Chemistry
wherein
X1 and X2 are each independently carbon or nitrogen;
Y is carbon, oxygen or nitrogen;
Z is carbon;
n is an integer of 0 or 1;
m is an integer of 0 to 2;
custom character is a single bond or a double bond;
R1 is -D-R10; wherein D is a direct bond, —O—, —C(═O)—, —C≡C— or —CR11R12—; R10 is hydrogen, halo, hydroxy, cyano, alkyl, hydroxyalkyl, haloalkyl, haloalkylsulfonate, dialkylamino, alkylaminoalkyl, dialkylaminoalkyl, dialkylaminocarbonylalkyl, saturated or unsaturated carbocyclyl, saturated or unsaturated heterocyclyl, saturated or unsaturated carbocyclyl-alkyl, or saturated or unsaturated heterocyclyl-alkyl; R11 and R12 are each independently hydrogen, hydroxy or alkyl; the carbocycle or heterocycle is optionally substituted with one or more substituents selected from hydroxy, halo, oxo, formyl (—CHO), nitrile, alkyl, alkoxy, hydroxyalkyl, hydroxyhaloalkyl, alkoxyalkyl, haloalkyl, nitrilealkyl, alkylcarbonyl, alkylthiocarbonyl, alkoxycarbonyl, haloalkylcarbonyl, carbocyclyl, carbocyclylcarbonyl, (alkyl)(haloalkyl)amino, (alkyl)(heterocyclyl)amino, heterocyclyl and heterocyclyl-alkyl;
R2 is hydrogen or alkyl;
R3 is hydrogen or alkyl;
R4, R5, R6 and R7 are each independently hydrogen or alkyl;
R8 is hydrogen, halo, alkyl, alkoxy or amino; and
R9 is hydrogen, halo or alkyl; and
wherein the disease associated with PRMT5 inhibition is selected from the group consisting of blood disease, autoimmune disease, inflammatory disease and neurodegenerative disease.