Patent RU-2684396-C2 (RU)
Title: Novel pyridopyrimidinone compounds for modulation of catalytic activity of histone lysine demethylases (kdms)
Inventor: KIM MYEONG-SEOP
IPC: C07D471/04
Filed: 2015-10-27
Granted: 2019-04-09
Abstract: FIELD: chemistry; pharmaceutics.SUBSTANCE: invention relates to a novel compound of formula (I), a stereoisomer thereof or a pharmaceutically acceptable salt thereof. In formula (I)X is selected from a group consisting of hydrogen, benzofuranyl, dihydrobenzofuranyl, chromanyl, dihydroindenyl, tetrahydronaphthalenyl, -CH(R)NH-Rand -CH(R)OR, where Ris hydrogen or Calkyl; where benzofuranyl can optionally be substituted with one R, where Ris C(=O)-O(R), where Ris Calkyl, or -C(=O)-N(R)(R), where Ris hydrogen and Ris Calkyl, substituted with 5-6-member heterocyclyl, having 1 N heteroatom; Y is H or -CHNH-AZ; A is selected from a group consisting of a single bond, Calkylene, Ccycloalkylene, 5-6-member heterocyclylene having 1 heteroatom N, -C(=O)- and -CHC(=O)-, where alkylene, cycloalkylene and heterocyclylene can optionally be substituted with one to three R, where Ris Calkyl, benzyl or amino; Z is selected from a group consisting of hydrogen, -N(R)(R), Calkyl, Ccycloalkyl, 4-6-member heterocyclyl, having 1 or 2 heteroatoms selected from a group consisting of N and O, 5-member heterocyclyl, having 1 heteroatom N and substituted with two adjacent substitutes R, which form 6-member heteroaryl ring having 1 N heteroatom; phenyl, benzyl and 5-6-member heteroaryl, having 1 or 2 heteroatoms selected from a group consisting of N, O and S, where alkyl, cycloalkyl, heterocyclyl, phenyl, benzyl and heteroaryl may optionally be substituted with one or two R, where Ris selected from a group consisting of halogen, Calkyl, Caminoalkyl, Chydroxyalkyl, Calkoxyalkyl, Ccycloalkyl, benzyl, oxo, C(=O)-O(R), -C(=O)-N(R)(R), -O(R), -N(R)(R), methylpiperidine and 5-6-member heterocyclyl, having 1 or 2 heteroatoms selected from a group consisting of N and O; Rselected from a group consisting of phenyl, benzyl, biphenyl, tetrahydronaphthalenyl, dihydroindenyl, 5-6-member heterocyclyl, having 1 heteroatom, selected from a group consisting of N and O, and 5-9 membered heteroaryl, having one or two heteroatoms selected from a group consisting of N or O, where each of said values Rcan optionally be substituted with one to three substitutes selected from halogen, Calkyl, Ccycloalkyl, -CF, -CN, -NO, -C(=O)-O(R), -C(=O)-N(R)(R), -O(R), -OCF, -N(R)(R), CalkoxySalkyl, -Calkyl-C(=O)R, -C(=O)R, -Calkyl-R, -NH-C(=O)R, -Calkyl-NRRand pyridinyl; Ror Ris independently selected from a group consisting of hydrogen, Calkyl, Caminoalkyl, dimethylaminopropyl, dimethylaminoethyl, Cfluoroalkyl, Chydroxyalkyl, Ccycloalkyl group(Ccycloalkyl)Calkyl, 5-6-member heterocyclyl, having 1 heteroatom O or N, phenyl, a group (5-6 membered heterocyclyl having 1 or 2 heteroatoms selected from N or CO)-Calkyl, (5-6-member heteroaryl, having 1 heteroatom N)-Calkyl and benzyl, where cycloalkyl, heterocyclyl, phenyl, cycloalkylalkyl, heterocyclylalkyl, heteroarylalkyl and benzyl can optionally be substituted with one or more substituents independently selected from R, where Ris selected from a group consisting of amino, Calkyl, Calkoxy, Calkoxyalkyl, Caminoalkyl, Cfluoroalkyl, Chydroxyalkyl, Ccycloalkyl, acetyl, benzyl, 5-6-member heterocyclyl, having one N heteroatom; or, alternatively, adjacent Rand Rform 5-6-member N-containing heterocyclyl which can additionally contain 1 heteroatom selected from N and O, and which is optionally substituted with R, where Ris selected from Calkyl, benzyl, Calkoxy, with the proviso that X is not hydrogen when Y is hydrogen; and when Y is H, X is -CH(R)OR, Ris H, and Ris phenyl, then such phenyl is substituted with one to three substitutes selected from Calkyl, Ccycloalkyl, -CF, -CN, -NO, -C(=O)-O(R), -C(=O)-N(R)(R), -O(R), -OCF, -N(R)(R), CalkoxySalkyl, -Calkyl-C(=O)R, -C(=O)R, -Calkyl-R, -NH-C(=O)R, pyridinyl and -Calkyl-NRR, and this substituted phenyl can additionally be substituted with halogen.EFFECT: compounds have histoneLysine demethylase (KDM) inhibitor activity and can be used for treating cancer or KDM dysregulated disease, in particular for treating cancer, selected from a group consisting of prostate cancer, lung cancer, breast cancer, stomach cancer, cervical cancer, melanoma, renal cell carcinoma and leukemia.9 cl, 2 dwg, 3 tbl, 241 exформула - formula