2. Academic Validation
  3. New tetrahydrobenzindoles as potent and selective 5-HT(7) antagonists with increased In vitro metabolic stability

New tetrahydrobenzindoles as potent and selective 5-HT(7) antagonists with increased In vitro metabolic stability

  • Bioorg Med Chem Lett. 2003 Jan 6;13(1):61-4. doi: 10.1016/s0960-894x(02)00842-9.
Chika Kikuchi 1,  Hisashi Suzuki,  Toyokazu Hiranuma,  Masao Koyama
Affiliations

Affiliation

  • 1 Pharmaceutical Research Center, Meiji Seika Kaisha Ltd., 760Morooka-cho, Kohoku-ku, Yokohama 222-8567, Japan. [email protected]
PMID: 12467617 DOI: 10.1016/s0960-894x(02)00842-9
Abstract

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.

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