Three-dimensional pharmacophore hypotheses for the locust neuronal octopamine receptor (OAR3). Part 2: Agonists

Akinori Hirashima, Canping Pan, Eiichi Kuwano, Eiji Taniguchi, Morifusa Eto

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

Abstract

Three-dimensional pharmacophore hypotheses were built from a set of 43 agonists against octopamine receptor class 3 (OAR3) in locust nervous tissue. Among the 10 chemical-featured models generated by program Catalyst/Hypo, a hypothesis including hydrogen-bond acceptor (HBA), hydrophobic (Hp), and hydrophobic aliphatic (HpAl) features was considered to be important and predictive in evaluating OAR3 agonists. While the ideal and null hypotheses had a cost of 156.40 and 239.20, respectively, the 10 resulting hypotheses possessed costs from 169.89 to 175.81. The best hypothesis that was confirmed to have a 95% chance of true correlation yielded a low RMS of 0.757 and high regression r of 0.933. Active agonists mapped well onto all the features of the hypothesis such as HBA, Hp, and HpAl. On the other hand, inactive compounds were shown to be difficult to achieve the energetically favorable conformation which is found in the active molecules in order to fit the 3-D chemical feature pharmacophore models. Copyright (C) 1999 Elsevier Science Ltd.

Original languageEnglish
Pages (from-to)1437-1443
Number of pages7
JournalBioorganic and Medicinal Chemistry
Volume7
Issue number7
DOIs
Publication statusPublished - Jul 1999

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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