Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 51, Issue 15, Pages 4708-4714Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jm800422v
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Funding
- NHLBI NIH HHS [R37 HL036235, R37HL036235, R01 HL036235, R01 HL036235-19] Funding Source: Medline
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We report a series of inhibitors of secreted phospholipases A(2) (sPLA(2)S) based on substituted indoles, 6,7-benzoindoles, and indolizines derived from LY315920, a well-known indole-based sPLA(2) 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 HE specific inhibitors and a substituted 6,7-benzoindole that inhibits nearly all human and mouse sPLAs in the low nanomolar range.
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