Chika Kikuchi

Tetrahydrothienopyridylbutyl-tetrahydrobenzindoles: New Selective Ligands of the 5-HT7 Receptor

The synthesis and the affinity for the 5-HT(7) receptor and other receptors of a novel series of fused-ring tetrahydropyridine derivatives are described. Some of the compounds showed high affinity for the 5-HT(7) receptor. Tetrahydrothienopyridylbutyl-tetrahydrobenzindoles and are potent ligands for the 5-HT(7) receptor, with high selectivity over the 5-HT(2) receptor and other receptors. These compounds should be useful tools for clarifying the biological role of the 5-HT(7) receptor.

New tetrahydrobenzindoles as potent and selective 5-HT7 antagonists with increased In vitro metabolic stability

Chemical modifications of compound 1 (DR4004), a potent, selective antagonist of the 5-HT(7) receptor, were conducted with the aim of improving its metabolic stability. Halogenation of putative sites of oxidative metabolism afforded compounds 7-10, which retained high affinity and selectivity for the 5-HT(7) receptor, and showed increased in vitro metabolic stability. Compound 10 (DR4485) showed oral bioavailability, and should be a useful tool for evaluating the therapeutic potential of 5-HT(7) antagonists.