Identification of potent type I MetAPs inhibitors by simple bioisosteric replacement. Part 2: SAR studies of 5-heteroalkyl substituted TCAT derivatives

Yong-Mei Cui; Qing-Qing Huang; Jie Xu; Ling-Ling Chen; Jing-Ya Li; Qi-Zhuang Ye; Jia Li; Fa-Jun Nan

doi:10.1016/j.bmcl.2005.06.005

Identification of potent type I MetAPs inhibitors by simple bioisosteric replacement. Part 2: SAR studies of 5-heteroalkyl substituted TCAT derivatives

Bioorg Med Chem Lett. 2005 Sep 15;15(18):4130-5. doi: 10.1016/j.bmcl.2005.06.005.

Authors

Yong-Mei Cui¹, Qing-Qing Huang, Jie Xu, Ling-Ling Chen, Jing-Ya Li, Qi-Zhuang Ye, Jia Li, Fa-Jun Nan

Affiliation

¹ 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.

PMID: 16005224
DOI: 10.1016/j.bmcl.2005.06.005

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alkylation
Aminopeptidases / antagonists & inhibitors*
Aminopeptidases / metabolism
Inhibitory Concentration 50
Isomerism
Methionyl Aminopeptidases
Molecular Structure
Protease Inhibitors / chemical synthesis*
Protease Inhibitors / chemistry
Protease Inhibitors / pharmacology*
Structure-Activity Relationship
Thiazoles / chemistry*
Thiazoles / pharmacology*

Substances

Protease Inhibitors
Thiazoles
Aminopeptidases
Methionyl Aminopeptidases