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Journal of medicinal and pharmaceutical chemistry 2008-08-14

Highly specific and broadly potent inhibitors of mammalian secreted phospholipases A2.

Rob C Oslund, Nathan Cermak, Michael H Gelb

文献索引:J. Med. Chem. 51 , 4708, (2008)

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摘要

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.

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