Identification of potent type I MetAPs inhibitors by simple bioisosteric replacement. Part 2: SAR studies of 5-heteroalkyl substituted TCAT derivatives.
Systematic SAR studies on the thiazole ring 5-substituent of TCAT derivatives revealed that the introduction of a beta-alkoxy or an amino group enhanced the inhibitory activity significantly. The present compounds are representative of specific Co(II)-MetAP1 inhibitors. Before the physiologically relevant metal ions for MetAPs are established, these small molecular compounds could be used as tools for detailed biological studies.
Cui
Yong-Mei
YM
Chinese National Center for Drug Screening, Shanghai Institute of Materia Medica, Shanghai Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, 189 Guoshoujing Road, Zhangjiang Hi-Tech Park, Shanghai 201203, PR China.
Huang
Qing-Qing
QQ
Xu
Jie
J
Chen
Ling-Ling
LL
Li
Jing-Ya
JY
Ye
Qi-Zhuang
QZ
Li
Jia
J
Nan
Fa-Jun
FJ
D000478:Alkylation; D000626:Aminopeptidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020128:Inhibitory Concentration 50; D007536:Isomerism; D063208:Methionyl Aminopeptidases; D015394:Molecular Structure; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry* / Q000494:pharmacology*
D011480:Protease Inhibitors; D013844:Thiazoles; D000626:Aminopeptidases; D063208:Methionyl Aminopeptidases