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

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 5 was discovered as a moderate CETP inhibitor. The replacement of the amide linker by heterocyclic aromatics and then a series of N,N-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 30 exhibited excellent CETP inhibitory activity (IC50 = 0.79 ± 0.02 μM) in vitro and showed an acceptable metabolic stability.

• Authors: Xinran Wang, Xuehua Lin, Xuanqi Xu, Wei Li, Lijuan Hao, Chunchi Liu, Dongmei Zhao, Maosheng Cheng
• Journal: Molecules (Basel, Switzerland) (Molecules) Vol. 22 Issue 11 (Nov 07 2017) ISSN: 1420-3049 [Electronic] Switzerland
• PMID: 29112169 (Publication Type: Journal Article)

Chemical References

• Cholesterol Ester Transfer Proteins
• Methylamines

Topics

• Animals
• Cholesterol Ester Transfer Proteins (antagonists & inhibitors)
• Drug Design
• Humans
• Methylamines (chemical synthesis, chemistry, pharmacology)
• Molecular Structure
• Rats
• Structure-Activity Relationship