5-Acyloxy-5-hydroxymethyltetrahydro-2-furancarboxylate as a novel template for protein kinase C (PKC) binding

• Published in: Farmaco (Società chimica italiana : 1989) Vol. 56; no. 3; pp. 203 - 210
• Main Authors: Lee, Jeewoo, Han, Kee-Chung, Lee, Sang-Yoon, Kim, Su-Yeon, Kang, Ji-Hye, Lewin, Nancy E., Best, Lionel S., Blumberg, Peter M., Marquez, Victor E.
• Format: Journal Article
• Language: English
• Published: Lausanne Elsevier SAS 01-03-2001; Elsevier Science
• Subjects: Binding, Competitive; Biological and medical sciences; Carboxylic Acids - chemical synthesis; Carboxylic Acids - chemistry; Diacylglycerol–lactones; Furans - chemical synthesis; Furans - chemistry; Kinetics; Ligands; Medical sciences; Miscellaneous; Models, Molecular; Molecular Conformation; Pharmacology. Drug treatments; Pharmacophore model; Phorbol 12,13-Dibutyrate; Phorbol ester; PKC ligands; Protein Binding; Protein kinase C; Protein Kinase C - metabolism; Templates, Genetic; Protein kinase C; Diacylglycerol–lactones; Pharmacophore model; Phorbol ester; PKC ligands; Stereoisomer; Five membered ring; Enzyme; Transferases; Oxygen heterocycle; In vitro; Biological activity; Primary alcohol; Signal transduction; Biological fixation; Chemical synthesis; Acylate
• ISSN: 0014-827X; 1879-0569
• DOI: 10.1016/S0014-827X(01)01077-1

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-α and a conformational fit to phorbol ester indicates they mimic a pharmacophore model comprising the C
20–OH, C
3–CO and C
9–OH rather than that including the C
13–CO moiety.