Design, Synthesis, and Biological Evaluation of N,N-Disubstituted-4-Arylthiazole-2-Methylamine Derivatives as Cholesteryl Ester Transfer Inhibitors
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 li...
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/22/11/1925 |
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doaj-b83f7b84d7504f238fa852f0b4fb52d32020-11-25T00:46:08ZengMDPI AGMolecules1420-30492017-11-012211192510.3390/molecules22111925molecules22111925Design, Synthesis, and Biological Evaluation of N,N-Disubstituted-4-Arylthiazole-2-Methylamine Derivatives as Cholesteryl Ester Transfer InhibitorsXinran Wang0Xuehua Lin1Xuanqi Xu2Wei Li3Lijuan Hao4Chunchi Liu5Dongmei Zhao6Maosheng Cheng7Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, ChinaKey Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, ChinaDepartment of Chemistry, University of Wisconsin-Madison, Madison, WI 53715, USAKey Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, ChinaKey Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, ChinaKey Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, ChinaKey Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, ChinaKey Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, ChinaCholesteryl 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.https://www.mdpi.com/1420-3049/22/11/1925synthesisN,N-disubstituted-4-arylthiazole-2-methylamine derivativesCETP inhibitors |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Xinran Wang Xuehua Lin Xuanqi Xu Wei Li Lijuan Hao Chunchi Liu Dongmei Zhao Maosheng Cheng |
| spellingShingle |
Xinran Wang Xuehua Lin Xuanqi Xu Wei Li Lijuan Hao Chunchi Liu Dongmei Zhao Maosheng Cheng Design, Synthesis, and Biological Evaluation of N,N-Disubstituted-4-Arylthiazole-2-Methylamine Derivatives as Cholesteryl Ester Transfer Inhibitors Molecules synthesis N,N-disubstituted-4-arylthiazole-2-methylamine derivatives CETP inhibitors |
| author_facet |
Xinran Wang Xuehua Lin Xuanqi Xu Wei Li Lijuan Hao Chunchi Liu Dongmei Zhao Maosheng Cheng |
| author_sort |
Xinran Wang |
| title |
Design, Synthesis, and Biological Evaluation of N,N-Disubstituted-4-Arylthiazole-2-Methylamine Derivatives as Cholesteryl Ester Transfer Inhibitors |
| title_short |
Design, Synthesis, and Biological Evaluation of N,N-Disubstituted-4-Arylthiazole-2-Methylamine Derivatives as Cholesteryl Ester Transfer Inhibitors |
| title_full |
Design, Synthesis, and Biological Evaluation of N,N-Disubstituted-4-Arylthiazole-2-Methylamine Derivatives as Cholesteryl Ester Transfer Inhibitors |
| title_fullStr |
Design, Synthesis, and Biological Evaluation of N,N-Disubstituted-4-Arylthiazole-2-Methylamine Derivatives as Cholesteryl Ester Transfer Inhibitors |
| title_full_unstemmed |
Design, Synthesis, and Biological Evaluation of N,N-Disubstituted-4-Arylthiazole-2-Methylamine Derivatives as Cholesteryl Ester Transfer Inhibitors |
| title_sort |
design, synthesis, and biological evaluation of n,n-disubstituted-4-arylthiazole-2-methylamine derivatives as cholesteryl ester transfer inhibitors |
| publisher |
MDPI AG |
| series |
Molecules |
| issn |
1420-3049 |
| publishDate |
2017-11-01 |
| description |
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. |
| topic |
synthesis N,N-disubstituted-4-arylthiazole-2-methylamine derivatives CETP inhibitors |
| url |
https://www.mdpi.com/1420-3049/22/11/1925 |
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