Benzhydrylquinazolinediones: Novel cytosolic phospholipase A 2 α inhibitors with improved physicochemical properties
SJ Kirincich, J Xiang, N Green, S Tam, HY Yang…
Index: Kirincich, Steven J.; Xiang, Jason; Green, Neal; Tam, Steve; Yang, Hui Y.; Shim, Jaechul; Shen, Marina W.H.; Clark, James D.; McKew, John C. Bioorganic and Medicinal Chemistry, 2009 , vol. 17, # 13 p. 4383 - 4405
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Citation Number: 23
Abstract
The synthesis and optimization of a class of trisubstituted quinazoline-2, 4 (1H, 3H)-dione cPLA2α inhibitors are described. Utilizing pharmacophores that were found to be important in our indole series, we discovered inhibitors with reduced lipophilicity and improved aqueous solubility. These compounds are active in whole blood assays, and cell-based assay results indicate that prevention of arachidonic acid release arises from selective ...
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