2-Benzyl and 2-phenyl-3-hydroxypropyl pivalates as protein kinase C ligands

A series of 2-benzyl and 2-phenyl-3-hydroxypropyl pivalates designed to incorporate the principal pharmacophores of phorbol esters have been synthesized and tested as PKC-α ligands. Among the analogues, 13c exhibited the most potent binding affinity with a K i = 0.7 μM. The synthesized analogues wer...

Ausführliche Beschreibung

Gespeichert in:

Bibliographische Detailangaben
Veröffentlicht in:	Bioorganic & medicinal chemistry 2006-03, Vol.14 (6), p.2022-2031
Hauptverfasser:	Lee, Jeewoo, Lee, Ju-Hyun, Kim, Su Yeon, Perry, Nicholas A., Lewin, Nancy E., Ayres, Jolene A., Blumberg, Peter M.
Format:	Artikel
Sprache:	eng
Schlagworte:	Binding Sites Biological and medical sciences Diacylglycerol Ligands Medical sciences Miscellaneous Models, Molecular Molecular Structure Pentanoic Acids - chemical synthesis Pentanoic Acids - chemistry Pentanoic Acids - metabolism Pharmacology. Drug treatments Phorbol ester Phorbols - chemistry Phorbols - metabolism Protein kinase C Protein Kinase C-alpha - chemistry Protein Kinase C-alpha - drug effects Protein Kinase C-alpha - metabolism Structure-Activity Relationship
Online-Zugang:	Volltext
Tags:	Tag hinzufügen Keine Tags, Fügen Sie den ersten Tag hinzu!

Beschreibung
Zusammenfassung:	A series of 2-benzyl and 2-phenyl-3-hydroxypropyl pivalates designed to incorporate the principal pharmacophores of phorbol esters have been synthesized and tested as PKC-α ligands. Among the analogues, 13c exhibited the most potent binding affinity with a K i = 0.7 μM. The synthesized analogues were subjected to molecular modeling analysis based on two alternative models of the phorbol pharmacophore and a docking study of 13c was carried out.
ISSN:	0968-0896 1464-3391
DOI:	10.1016/j.bmc.2005.10.051