New tetrahydrobenzindoles as potent and selective 5-HT(7) antagonists with increased In vitro metabolic stability
Chika Kikuchi1, Hisashi Suzuki, Toyokazu Hiranuma
1Pharmaceutical Research Center, Meiji Seika Kaisha Ltd., 760Morooka-cho, Kohoku-ku, Yokohama 222-8567, Japan. chika_kikuchi@meiji.co.jp
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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