Highly Specific and Broadly Potent Inhibitors of Mammalian Secreted Phospholipases A2
- 8 July 2008
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 51 (15) , 4708-4714
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.Keywords
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