Work

Highly Specific and Broadly Potent Inhibitors of Mammalian Secreted Phospholipases A2

Year: 2008

Type: article

Abstract: We report a series of inhibitors of secreted phospholipases A2 (sPLA2s) based on substituted indoles, 6,7-benzoindoles, and indolizines derived from LY315920, a well-known indole-based sPLA2 inhibitor. Using the human group X sPLA2 crystal structure, we prepared a highly potent and selective indole-based inhibitor of this enzyme. Also, we report human and mouse group IIA and IIE specific inhibitors and a substituted 6,7-benzoindole that inhibits nearly all human and mouse sPLA2s in the low nanomolar range.

Source: Journal of Medicinal Chemistry

DOI: 10.1021/jm800422v

Authors: Rob C. Oslund, Nathan Cermak, Michael H. Gelb

Institution: University of Washington

Language: English

Topic: Synthesis and biological activity

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: green

Funder: National Heart, Lung, and Blood Institute