Inhibitors of type I MetAPs containing pyridine-2-carboxylic acid thiazol-2-ylamide. Part 2: SAR studies on the pyridine ring 3-substituent.
Systematic SAR studies on the pyridine ring 3-substituent of PCAT, an inhibitor of EcMetAP1 and ScMetAP1, revealed that 3-substituents have different selectivity for EcMetAP1 and ScMetAP1. The selective inhibitors of type I MetAP are useful tools for investigating the detailed interactions between the enzymes and their inhibitors. In addition, these findings provide useful information for the design and discovery of more potent inhibitors of type I MetAPs.
Luo
Qun-Li
QL
Chinese National Center for Drug Screening, Chinese Academy of Sciences, 189 Guoshoujing Road, Zhangjiang Hi-Tech Park, Shanghai 201203, PR China.
Li
Jing-Ya
JY
Chen
Ling-Ling
LL
Li
Jia
J
Ye
Qi-Zhuang
QZ
Nan
Fa-Jun
FJ
D000626:Aminopeptidases / Q000037:antagonists & inhibitors*; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000494:pharmacology; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors; D004926:Escherichia coli / Q000201:enzymology; D006801:Humans; D020128:Inhibitory Concentration 50; D063208:Methionyl Aminopeptidases; D011725:Pyridines / Q000138:chemical synthesis / Q000494:pharmacology; D012486:Salmonella typhimurium / Q000201:enzymology; D013329:Structure-Activity Relationship; D013854:Thioamides / Q000138:chemical synthesis* / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D001426:Bacterial Proteins; D011725:Pyridines; D013854:Thioamides; D000626:Aminopeptidases; D063208:Methionyl Aminopeptidases