一系列四取代咪唑作为 P2X(7)拮抗剂的合成及生物活性。

Synthesis and biological activity of a series of tetrasubstituted-imidazoles as P2X(7) antagonists.

机构信息

Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, UK.

出版信息

Bioorg Med Chem Lett. 2010 Aug 15;20(16):4951-4. doi: 10.1016/j.bmcl.2010.05.018. Epub 2010 Jun 25.

DOI:10.1016/j.bmcl.2010.05.018

PMID:20634071

Abstract

A series of analogues of the pyrazole lead 1 were synthesized in which the heterocyclic core was replaced with an imidazole. A number of potent antagonists were identified and structure-activity relationships (SAR) were investigated both with respect to activity at the P2X(7) receptor and in vitro metabolic stability. Compound 10 was identified as a potent P2X(7) antagonist with reduced in vitro metabolism and high solubility.

摘要

一系列吡唑先导化合物 1 的类似物被合成，其中杂环核心被咪唑取代。鉴定出了一些有效的拮抗剂，并研究了它们在 P2X(7)受体上的活性以及体外代谢稳定性方面的构效关系（SAR）。化合物 10 被鉴定为一种有效的 P2X(7)拮抗剂，具有降低的体外代谢和高溶解度。

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一系列四取代咪唑作为 P2X(7)拮抗剂的合成及生物活性。

Synthesis and biological activity of a series of tetrasubstituted-imidazoles as P2X(7) antagonists.

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