当前位置： SCI文献检索 > JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > 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.

Abstract：

:Transient receptor potential canonical 3/6/7 (TRPC3/6/7) are highly homologous receptor-operated nonselective 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.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

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

doi

10.1021/acs.jmedchem.7b00304

subject

Has Abstract

pub_date

2017-06-08 00:00:00

pages

4680-4692

issue

11

eissn

0022-2623

issn

1520-4804

journal_volume

60

pub_type

杂志文章

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