Design, synthesis and preliminary evaluation of novel pyrrolidine derivatives as matrix metalloproteinase inhibitors

Xian-Chao Cheng; Qiang Wang; Hao Fang; Wei Tang; Wen-Fang Xu

doi:10.1016/j.ejmech.2007.12.020

Design, synthesis and preliminary evaluation of novel pyrrolidine derivatives as matrix metalloproteinase inhibitors

Eur J Med Chem. 2008 Oct;43(10):2130-9. doi: 10.1016/j.ejmech.2007.12.020. Epub 2007 Dec 31.

Authors

Xian-Chao Cheng¹, Qiang Wang, Hao Fang, Wei Tang, Wen-Fang Xu

Affiliation

¹ Institute of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, No. 44 Wenhuaxi Road, Jinan 250012, China. chengxianchao2000@yahoo.com.cn

PMID: 18362041
DOI: 10.1016/j.ejmech.2007.12.020

Abstract

A series of novel pyrrolidine derivatives were designed, synthesized and assayed for their inhibitory activities on matrix metalloproteinase 2 (MMP-2) and aminopeptidase N (AP-N). The results showed that these pyrrolidine derivatives exhibited highly selective inhibition against MMP-2 as compared with AP-N. The hydroxamates 8a-c were equally or more potent MMP-2 inhibitors than the positive control LY52. The binding mode of the most potent compound 8a with MMP-2 was proposed. Structure-activity relationships were also briefly discussed.

Publication types

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

MeSH terms

Amino Acid Sequence
CD13 Antigens / antagonists & inhibitors
CD13 Antigens / chemistry
Drug Design*
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
Matrix Metalloproteinase 2 / chemistry
Matrix Metalloproteinase Inhibitors*
Matrix Metalloproteinases / chemistry
Models, Molecular
Molecular Conformation
Pyrrolidines / chemical synthesis*
Pyrrolidines / chemistry
Pyrrolidines / pharmacology*

Substances

Enzyme Inhibitors
Matrix Metalloproteinase Inhibitors
Pyrrolidines
CD13 Antigens
Matrix Metalloproteinases
Matrix Metalloproteinase 2
pyrrolidine