Document Report Card

ID: ALA1134299

Journal: J Med Chem

Title: Conformationally constrained analogues of diacylglycerol. 18. The incorporation of a hydroxamate moiety into diacylglycerol-lactones reduces lipophilicity and helps discriminate between sn-1 and sn-2 binding modes to protein kinase C (PK-C). Implications for isozyme specificity.

Authors: Lee J, Han KC, Kang JH, Pearce LL, Lewin NE, Yan S, Benzaria S, Nicklaus MC, Blumberg PM, Marquez VE.

Abstract: An approach to reduce the log P in a series of diacylglycerol (DAG)-lactones known for their high binding affinity for protein kinase C (PK-C) is presented. Branched alkyl groups with reduced lipophilicity were selected and combined with the replacement of the ester or lactone oxygens by NH or NOH groups. Compound 6a with an isosteric N-hydroxyl amide arm represents the most potent and least lipophilic DAG analogue known to date.

CiteXplore: 11728178

DOI: 10.1021/jm0103965