Pyrazolopyrimidines as Potent Stimulators for Transient Receptor Potential Canonical 3/6/7 Channels.
Pyrazolopyrimidines as Potent Stimulators for Transient Receptor Potential Canonical 3/6/7 Channels.
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吡唑并嘧啶作为瞬时受体电位规范 3/6/7 通道的有效刺激剂
DOI：
10.1021/acs.jmedchem.7b00304
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发表时间：
2017-06-08
影响因子：
7.3
通讯作者：
Hong X
中科院分区：
文献类型：
--
作者：
Qu C;Ding M;Zhu Y;Lu Y;Du J;Miller M;Tian J;Zhu J;Xu J;Wen M;Er-Bu A;Wang J;Xiao Y;Wu M;McManus OB;Li M;Wu J;Luo HR;Cao Z;Shen B;Wang H;Zhu MX;Hong X
Transient receptor potential canonical 3/6/7 (TRPC3/6/7) are highly homologous receptor-operated non-selective cation channels. Despite their physiological significance, very few selective and potent agonists are available for functional examination of these channels. Using a cell-based high throughput screening approach, a lead compound with the pyrazolopyrimidine skeleton was identified as a TRPC6 agonist. Synthetic schemes for the lead and its analogues were established, and structural–activity relationship studies were carried out. A series of potent and direct agonists of TRPC3/6/ 7 channels were identified, and among them, 4m–4p have a potency order of TRPC3 > C7 > C6, with 4n being the most potent with an EC50 of <20 nM on TRPC3. Importantly, these compounds exhibited no stimulatory activity on related TRP channels. The potent and selective compounds described here should be suitable for evaluation of the roles of TRPC channels in the physiology and pathogenesis of diseases, including glomerulosclerosis and cancer.
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DOI：
10.1002/anie.201411511
发表时间：
2015-03-16
期刊：
Angewandte Chemie (International ed. in English)
影响因子：
--
作者：
Akbulut Y;Gaunt HJ;Muraki K;Ludlow MJ;Amer MS;Bruns A;Vasudev NS;Radtke L;Willot M;Hahn S;Seitz T;Ziegler S;Christmann M;Beech DJ;Waldmann H
通讯作者：
Waldmann H
影响因子：
7.3
作者：
Maier, T.;Follmann, M.;Struebing, C.
通讯作者：
Struebing, C.
影响因子：
4.8
作者：
Miller, Melissa;Shi, Jie;Zhu, Michael X.
通讯作者：
Zhu, Michael X.
影响因子：
2.7
作者：
Harada, H;Yamazaki, H;Kato, S
通讯作者：
Kato, S
影响因子：
30.8
作者：
Reiser, J;Polu, KR;Pollak, MR
通讯作者：
Pollak, MR