Synthesis of 4-phenoxy quinoline mevalonolactones and evaluation of their HMG CoA reductase inhibition activities

Abstract

Abstract: A series of 4-phenoxy quinoline-based mevalonolactone derivatives have been synthesized and evaluated as 3-hydroxy-3-methylglutaryl CoA reductase (HMG CoA reductase) inhibitors. One member of this series, (4R,6S)-6-{(E)-2-[6-fluoro-7-chloro-4-(4-fluorophenoxy-quinoline)-3-yl-]-ethenyl}-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one (3d), showed more potent activity than rosuvastatin or pitavastatin to inhibit the rat HMG CoA reductase in vitro. This compound was selected for the extensive preclinical development as a potential hypocholesterolemic candidate.

Key words: HMG CoA reductase inhibitors, 4-Phenoxy quinolines, Synthesis

CLC Number:

R916.41

Supporting:

Zheng-Yan Cai^*, Jing Pan, Qun Hao, Wei-Cheng Zhou, Lu-Yong Zhang. Synthesis of 4-phenoxy quinoline mevalonolactones and evaluation of their HMG CoA reductase inhibition activities [J]. .

[1]	Yuxia Zhu, Lingjian Zhang, Yiming Hu, Weihua Liu, Liping Guan, Lin Lin. Study on synthesis of naringenin derivatives and cholinesterase inhibitory activity in marine Chinese medicine [J]. Journal of Chinese Pharmaceutical Sciences, 2023, 32(8): 636-644.
[2]	Ao Sun, Zipeng Li, Ting Liu, Xiangbao Meng, Shuchun Li, Zhongjun Li. Improvement of Kdo's efficient large-scale chemical synthesis method [J]. Journal of Chinese Pharmaceutical Sciences, 2022, 31(2): 97-107.
[3]	Huijie Lv, Tuo Xv, Jun Peng, Gang Luo, Jianqin He, Sisi Yang, Tiancheng Zhang, Shuidong Feng, Hongyan Ling. Dihydromyricetin improves liver fat deposition in high-fat diet-induced obese mice [J]. Journal of Chinese Pharmaceutical Sciences, 2022, 31(11): 824-839.
[4]	Yuehua Liu, Zhangqin Xue, Jianming Wei, Ruomeng Wei, Baodong Yin, Aiqin Liu. Study on drug synthesis and activity of sodium olpadronate [J]. Journal of Chinese Pharmaceutical Sciences, 2022, 31(11): 883-892.
[5]	Lijuan Jiang, Tingting Cao, Ruoyi Yang, Ying Li, Lin Dong, Shufan Yin. Design, synthesis, and biological evaluation of a series of novel cordycepin derivatives [J]. Journal of Chinese Pharmaceutical Sciences, 2022, 31(1): 55-67.
[6]	Shiqi Xu, Liyan Zhu, Chao Hao, Wenqian Liu, Chenglong Chen, Yongyi Chen, Aiqin Liu. Synthesis of a novel series of amino acid prodrugs based on tegafur and evaluation of their antitumor activity [J]. Journal of Chinese Pharmaceutical Sciences, 2021, 30(9): 743-753.
[7]	State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Health Science Center. Cyclic peptide molecular biosynthesis-the group of Professor Ming Ma discovered the first catalytic isomerization/cyclic bifunctional thioesterase and analyzed its crystal structure [J]. Journal of Chinese Pharmaceutical Sciences, 2021, 30(9): 778-779.
[8]	Xueni Cai, Ge Fu, Martin Lepšík, Emanuele Paci, Yuan Guo, Zhongjun Li, Qing Li. Synthesis of a series of novel homo- and hetero-glycoclusters and their binding activities to DC-SIGN [J]. Journal of Chinese Pharmaceutical Sciences, 2021, 30(11): 859-873.
[9]	Beidou Zhou, Jiali Li, Baocheng Huang, Zihan Yu, Zetong Ma, Zhipeng Ruan, Qihong Cai, Dongbao Hu. Syntheses of phenyl benzoate compounds and their bioactivity investigation [J]. Journal of Chinese Pharmaceutical Sciences, 2021, 30(11): 874-882.
[10]	Wanjun Yan, Wenming Li, Decai Xiong, Xinshan Ye. Design, synthesis and evaluation of carbamate-containing sialyltransferase inhibitors [J]. Journal of Chinese Pharmaceutical Sciences, 2020, 29(1): 29-44.
[11]	Zhongyi Zhang, Hanxuan Wang, Guiyang Wang, Xueyang Ma, Tan Liu, Tongtong Geng, Xiaoxu Sun, Donghui Yang, Suwei Dong, Ming Ma. Synthesis of two substrate mimics of thioesterase in the biosynthesis of cyclic depsipeptide WS9326A [J]. Journal of Chinese Pharmaceutical Sciences, 2019, 28(9): 605-614.
[12]	Xupeng Yang, Zhenzhen Yang, Lu Zhang, Qi Sun, Xianrong Qi. Tunable gold nanostar synthesis with surfactant-free system [J]. Journal of Chinese Pharmaceutical Sciences, 2019, 28(9): 641-649.
[13]	Weihao Ma, Zhi Huang, Yanxing Jia. Improved synthesis of key intermediate of grayanotoxin III [J]. Journal of Chinese Pharmaceutical Sciences, 2019, 28(6): 402-407.
[14]	Hui Liu, Lei Liang, Lan Yuan, Fengrong Xu, Yan Niu, Chao Wang, Ping Xu. Design and synthesis of nitrogen-fused pyridazinone fluorescent probes and their application in biological imaging [J]. Journal of Chinese Pharmaceutical Sciences, 2019, 28(5): 298-315.
[15]	Beidou Zhou, Xin Wang, Zhimin Weng, Baocheng Huang, Zetong Ma, Bo Yu, Liqin Ruan, Dongbao Hu. Synthesis and antitumor, antityrosinase, and antiplatelet aggregation activities of xanthone [J]. Journal of Chinese Pharmaceutical Sciences, 2019, 28(4): 247-256.

Synthesis of 4-phenoxy quinoline mevalonolactones and evaluation of their HMG CoA reductase inhibition activities

PDF (PC)

Knowledge

Cited

Abstract

Cite this article

share this article

References

Related Articles 15

Recommended Articles

Metrics

Comments