Premium
Discovery of a novel class of pyridine derivatives that selectively inhibits mutant isocitrate dehydrogenase 2
Author(s) -
Wang Fangying,
Li Zhuoling,
Zhang Tao,
Yan Guoyi,
Hu Mingxing,
Zhao Lifeng,
Zhao Yinglan,
Chen Yuanwei
Publication year - 2018
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.13139
Subject(s) - isocitrate dehydrogenase , mutant , pyridine , chemistry , drug discovery , combinatorial chemistry , biochemistry , computational biology , stereochemistry , enzyme , biology , organic chemistry , gene
This paper presents synthesis and structure–activity relationship of pyridine derivatives as inhibitors of mutant isocitrate dehydrogenase 2 ( IDH 2). A series of 2,4,6‐trisubstituted pyridine derivatives have been prepared and evaluated in vitro. Among these compounds, 14n exhibited excellent inhibition activity with the IC 50 of 54.6 n m , which is approximately onefold improvement compared to drug candidate AG ‐221 (Enasidenib) that is in Phase III trial. Exquisite selectivity of 14n for IDH 2 R140Q mutant isoform was demonstrated by the poor activity against the wild‐type IDH 1 and IDH 2.
Accelerating Research
Robert Robinson Avenue,
Oxford Science Park, Oxford
OX4 4GP, United Kingdom
Address
John Eccles HouseRobert Robinson Avenue,
Oxford Science Park, Oxford
OX4 4GP, United Kingdom