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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
4-Butyrolactone / analogs & derivatives
-
4-Butyrolactone / chemistry*
-
Diglycerides / chemical synthesis*
-
Diglycerides / chemistry
-
Drug Design
-
Hydroxamic Acids / chemistry*
-
Isoenzymes / chemistry
-
Lactones / chemical synthesis*
-
Lactones / chemistry
-
Ligands
-
Models, Molecular
-
Molecular Conformation
-
Protein Binding
-
Protein Kinase C / chemistry*
-
Structure-Activity Relationship
Substances
-
4-((N-hydroxy(tert-butylcarbonyl)amino)methyl)-4-hydroxy-3-(3-(2-methylpropyl)hexylidene)-2-oxotetrahydrofuran
-
Diglycerides
-
Hydroxamic Acids
-
Isoenzymes
-
Lactones
-
Ligands
-
Protein Kinase C
-
4-Butyrolactone