Identification of potent type I MetAP inhibitors by simple bioisosteric replacement. Part 1: Synthesis and preliminary SAR studies of thiazole-4-carboxylic acid thiazol-2-ylamide derivatives.
A series of thiazole-4-carboxylic acid thiazol-2-ylamide (TCAT, 4) derivatives were designed and synthesized according to simple bioisosteric replacement from previously reported pyridine-2-carboxylic acid thiazol-2-ylamide (PCAT) MetAP inhibitors. The preliminary SAR studies demonstrated that these TCAT series of compounds showed different activity and selectivity compared with those of the corresponding PCAT compounds. These findings provide useful information for the design and discovery of more potent inhibitors of type I MetAPs.
Chinese National Center for Drug Screening, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 201203, PR China.
Yong-Mei
YM
Cui
Qing-Qing
QQ
Huang
Jie
J
Xu
Ling-Ling
LL
Chen
Jing-Ya
JY
Li
Qi-Zhuang
QZ
Ye
Jia
J
Li
Fa-Jun
FJ
Nan
D000626:Aminopeptidases / Q000037:antagonists & inhibitors*; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D004926:Escherichia coli / Q000201:enzymology; D063208:Methionyl Aminopeptidases; D015394:Molecular Structure; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013854:Thioamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D013844:Thiazoles; D013854:Thioamides; D000626:Aminopeptidases; D063208:Methionyl Aminopeptidases