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
- 9 November 2001
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 44 (25), 4309-4312
- https://doi.org/10.1021/jm0103965
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.Keywords
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