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Benzoxepin derivatives: design, synthesis, and pharmacological evaluation with sedative–hypnotic effect

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Abstract

A series of novel benzoxepin-derived compounds were synthesized and evaluated for their sedative–hypnotic effect using Phenobarbital-induced sleep test in mice. Compound 6 in which the Phenobarbital moiety was incorporated into the benzoxepin nucleus was the most active one. Molecular modeling, including fitting to a 3D-pharmacophore model using Discovery Studio 2.1 programs into optimized benzodiazepine receptor (hypothesis) showed high fit values. The experimental studies for the in vivo sedative–hypnotic effect of compounds 2–6 and 11a–c were consistent with the molecular modeling.

Graphical abstract

A series of novel benzoxepin-derived compounds were synthesized and evaluated for their sedative–hypnotic effect using Phenobarbital-induced sleep test in mice. Compound 6 in which the Phenobarbital moiety was incorporated into the benzoxepin nucleus was the most active one.

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Acknowledgment

The authors express deep thanks to Dr. Nasser S.M. Ismail, Lecturer of Pharmaceutical Chemistry, Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ain Shams University for his kind help during the molecular modeling.

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Authors and Affiliations

  1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt

    Nagwa M. Abdel Gawad, Ghaneya S. Hassan & Hanan H. Georgey

  2. Department of Pharmacology, Faculty of Veterinary Medicine, Cairo University, Cairo, Egypt

    Hesham Y. El-Zorba

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  1. Nagwa M. Abdel Gawad
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  2. Ghaneya S. Hassan
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  3. Hanan H. Georgey
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  4. Hesham Y. El-Zorba
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Correspondence to Hanan H. Georgey.

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Abdel Gawad, N.M., Hassan, G.S., Georgey, H.H. et al. Benzoxepin derivatives: design, synthesis, and pharmacological evaluation with sedative–hypnotic effect. Med Chem Res 21, 747–759 (2012). https://doi.org/10.1007/s00044-011-9579-3

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  • DOI: https://doi.org/10.1007/s00044-011-9579-3

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