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Design and synthesis of imidazole and triazole derivatives as Lp-PLA₂ inhibitors and the unexpected discovery of highly potent quaternary ammonium salts.

Abstract：

:New Lp-PLA(2) inhibitors were synthesized by the bioisosteric replacement of the amide group of Darapladib with an imidazole or a triazole. Unfortunately, the inhibitory activities of these derivatives were lower than that of Darapladib. But interestingly, a series of quaternary ammonium salts that were isolated as by-products during this synthetic work were found with high potency. Of these by-products, compound 22c showed a similar profile to Darapladib both in vitro and in vivo.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Wang K,Xu W,Liu Y,Zhang W,Wang W,Shen J,Wang Y

doi

10.1016/j.bmcl.2013.01.029

subject

Has Abstract

pub_date

2013-03-01 00:00:00

pages

1187-92

issue

5

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(13)00051-6

journal_volume

23

pub_type

杂志文章

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