Atropisomerism in the Vaptan Class of Vasopressin Receptor Ligands: The Active Conformation Recognized by the Receptor

Authors

  • Hidetsugu Tabata,

    1. School of Pharmaceutical Sciences, Teikyo University, 1091-1 Midori-ku, Sagamihara, Kanagawa 252-5195 (Japan), Fax: (+81) 426-85-3728
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  • Jun Nakagomi,

    1. School of Pharmaceutical Sciences, Teikyo University, 1091-1 Midori-ku, Sagamihara, Kanagawa 252-5195 (Japan), Fax: (+81) 426-85-3728
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  • Daisuke Morizono,

    1. Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510 (Japan)
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  • Dr. Tetsuta Oshitari,

    1. School of Pharmaceutical Sciences, Teikyo University, 1091-1 Midori-ku, Sagamihara, Kanagawa 252-5195 (Japan), Fax: (+81) 426-85-3728
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  • Prof. Dr. Hideyo Takahashi,

    1. School of Pharmaceutical Sciences, Teikyo University, 1091-1 Midori-ku, Sagamihara, Kanagawa 252-5195 (Japan), Fax: (+81) 426-85-3728
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  • Prof. Dr. Hideaki Natsugari

    Corresponding author
    1. School of Pharmaceutical Sciences, Teikyo University, 1091-1 Midori-ku, Sagamihara, Kanagawa 252-5195 (Japan), Fax: (+81) 426-85-3728
    • School of Pharmaceutical Sciences, Teikyo University, 1091-1 Midori-ku, Sagamihara, Kanagawa 252-5195 (Japan), Fax: (+81) 426-85-3728
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  • We are grateful to Sagami Chemical Research Center for X-ray analysis. This work was supported in part by the Japan Society for the Promotion of Sciences by a Grant-in-Aid for Scientific Research (C) (21590124) and a Grant-in-Aid for Young Scientists (B) (21790025).

Abstract

original image

Verborgene Chiralität: Atropisomerie in der Vaptan-Klasse der Vasopressinrezeptorliganden mit benzanelliertem siebengliedrigem Stickstoffheterocyclus wurde nach Einfrieren der Rotation um die Molekülachse durch ortho-Substitution untersucht. Die aS,aR-Atropisomere, die an der Ar[BOND]N([DOUBLE BOND]CO)-Achse entstehen, wurden getrennt, um zu zeigen, dass der Vasopressinrezeptor die cis,aS-Konformation (siehe Bild) erkennt, wenn er den Liganden bindet.

Ancillary