Design, Synthesis, and Biological Evaluation of N,N-Disubstituted-4-Arylthiazole-2-Methylamine Derivatives As Cholesteryl Ester Transfer Inhibitors

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2017 Nov 8

PMID 29112169

Authors

Xinran Wang

Xuehua Lin

Xuanqi Xu

Wei Li

LiJuan Hao

Chunchi Liu

Dongmei Zhao

Maosheng Cheng

Affiliations

Soon will be listed here.

Abstract

Cholesteryl ester transfer protein (CETP) has been identified as a potential target for cardiovascular disease (CVD) for its important role in the reverse cholesteryl transfer (RCT) process. In our previous work, compound was discovered as a moderate CETP inhibitor. The replacement of the amide linker by heterocyclic aromatics and then a series of ,-substituted-4-arylthiazole-2-methylamine derivatives were designed by utilizing a conformational restriction strategy. Thirty-six compounds were synthesized and evaluated for their CETP inhibitory activities. Structure-activity relationship studies indicate that electron donor groups substituted ring A, and electron-withdrawing groups at the 4-position of ring B were critical for potency. Among these compounds, compound exhibited excellent CETP inhibitory activity (IC = 0.79 ± 0.02 μM) in vitro and showed an acceptable metabolic stability.

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