US 12,281,109 B2
Inhibitors of histone deacetylase-3 useful for the treatment of cancer, inflammation, neurodegeneration diseases and diabetes
Jian Liu, Edison, NJ (US); Younong Yu, East Brunswick, NJ (US); Joseph A. Kozlowski, Princeton, NJ (US); Deyou Sha, Yardley, PA (US); Wensheng Yu, Edison, NJ (US); Joseph M. Kelly, Parlin, NJ (US); and Scott E. Wolkenberg, Wyndmoor, PA (US)
Assigned to Merck Sharp & Dohme LLC, Rahway, NJ (US)
Appl. No. 17/598,342
Filed by Merck Sharp & Dohme LLC, Rahway, NJ (US)
PCT Filed Mar. 30, 2020, PCT No. PCT/US2020/025631
§ 371(c)(1), (2) Date Sep. 27, 2021,
PCT Pub. No. WO2020/205688, PCT Pub. Date Oct. 8, 2020.
Claims priority of provisional application 62/829,159, filed on Apr. 4, 2019.
Prior Publication US 2022/0177465 A1, Jun. 9, 2022
Int. Cl. A61P 25/28 (2006.01); A61P 29/00 (2006.01); A61P 31/18 (2006.01); A61P 35/00 (2006.01); C07D 401/14 (2006.01); C07D 405/14 (2006.01); C07D 417/12 (2006.01); C07D 417/14 (2006.01); C07D 487/04 (2006.01)
CPC C07D 417/12 (2013.01) [C07D 401/14 (2013.01); C07D 405/14 (2013.01); C07D 417/14 (2013.01); C07D 487/04 (2013.01)] 13 Claims
 
1. A compound of the formula:

OG Complex Work Unit Chemistry
wherein

OG Complex Work Unit Chemistry
is a five-membered heteroaryl ring which is optionally substituted with halo, cyano or C1-3 alkyl;

OG Complex Work Unit Chemistry
is phenyl or heteroaryl, which may be monocyclic or bicyclic, wherein said phenyl and heteroaryl groups are optionally substituted with one to three substituents independently selected from the group consisting of halo, oxo, cyano, R4, R6, OR4, NHR4, NR4R5, NO2 and SR4;
R1 is naphthalenyl or quinolinyl wherein said naphthalenyl and quinolinyl groups are optionally substituted with one to two groups independently selected from the group consisting of halo, oxo, cyano, R4 and OR4;
R2 is selected from the group consisting of NH(C═O)R6, NH(C═O)CH(CH3)R6 and NH(C═O)R4;
R3 is hydrogen or C1-6 alkyl;
or R2 and R3 can be taken together with the atoms to which they are attached to form a 5-membered heterocyclyl group which is optionally substituted with oxo;
each R4 is independently hydrogen or C1-6 alkyl, which is optionally substituted with one to three groups independently selected from the group consisting of halo, cyano and OR5;
each R5 is independently hydrogen or C1-6 alkyl;
R6 is
(a) heterocyclyl, which may be monocyclic or bicyclic,
(b) C3-6 cycloalkyl,
(c) phenyl, or
(d) heteroaryl, which may be monocyclic or bicyclic,
wherein said heterocyclyl, cycloalkyl, phenyl and heteroaryl groups are optionally substituted with one to two groups independently selected from the group consisting of oxo, R4 and OR4;
or a pharmaceutically acceptable salt thereof.