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
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.