Solid phase parallel synthesis of highly substituted thiophene derivativesand identification of novel phosphodiesterase-4 (PDE-4) inhibitors

Citation
Yx. Han et al., Solid phase parallel synthesis of highly substituted thiophene derivativesand identification of novel phosphodiesterase-4 (PDE-4) inhibitors, TETRAHEDRON, 55(39), 1999, pp. 11669-11685
Citations number
55
Categorie Soggetti
Chemistry & Analysis","Organic Chemistry/Polymer Science
Journal title
TETRAHEDRON
ISSN journal
00404020 → ACNP
Volume
55
Issue
39
Year of publication
1999
Pages
11669 - 11685
Database
ISI
SICI code
0040-4020(19990924)55:39<11669:SPPSOH>2.0.ZU;2-P
Abstract
A versatile protocol for solid phase synthesis of highly substituted thioph ene derivatives and their activity against the PDE-4 enzyme are discussed. This protocol employs 3-hydroxymethylthiophene-2-boronic acid (5) as the sc affold and sequential palladium catalyzed cross-coupling reactions as the C -C bond forming step. This methodology allows convenient modification of th e thiophene core from three directions, giving rise to structurally diverse derivatives with overall high chemical purity and yield. A novel series of potent PDE-4 inhibitors have been identified from these compounds. (C) 199 9 Published by Elsevier Science Ltd. All rights reserved.