5-acyloxy-5-hydroxymethyltetrahydro-2-furancarboxylate as a novel template for protein kinase C (PKC) binding.
A series of alkyl tetrahydrofuran-2-carboxylates (1-4) bearing a new set of three pharmacophoric groups were tested as protein kinase C (PKC) ligands. The compounds were synthesized from commercially available glycidyl 4-methoxyphenyl ether. The correlation between their binding affinities for PKC-alpha and a conformational fit to phorbol ester indicates they mimic a pharmacophore model comprising the C20-OH, C3-C=O and C9-OH rather than that including the C13-C=O moiety.
Lee
J
J
Laboratory of Medicinal Chemistry, College of Pharmacy, Seoul National University, Shinlim-Dong, Kwanak-Ku, Seoul 151-742, South Korea. jeewoo@snu.ac.kr
Han
K C
KC
Lee
S Y
SY
Kim
S Y
SY
Kang
J H
JH
Lewin
N E
NE
Best
L S
LS
Blumberg
P M
PM
Marquez
V E
VE
D001667:Binding, Competitive; D002264:Carboxylic Acids / Q000138:chemical synthesis* / Q000737:chemistry; D005663:Furans / Q000138:chemical synthesis* / Q000737:chemistry; D007700:Kinetics; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D015240:Phorbol 12,13-Dibutyrate; D011485:Protein Binding; D011493:Protein Kinase C / Q000378:metabolism*; D013698:Templates, Genetic
D002264:Carboxylic Acids; D005663:Furans; D008024:Ligands; D015240:Phorbol 12,13-Dibutyrate; C018674:tetrahydrofuran; D011493:Protein Kinase C