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Identification of the three-dimensional pharmacophore of kappa-opioid receptor agonists
Noriyuki Yamaotsu1, Hideaki Fujii, Hiroshi Nagase
1School of Pharmacy, Kitasato University, Minato-ku, Tokyo 108-8641, Japan. yamaotsun@pharm.kitasato-u.ac.jp
Abstract:
A selective kappa-opioid receptor agonist might act as a powerful analgesic without the side effects of mu-opioid receptor-selective drugs such as morphine. The eight classes of known kappa-opioid receptor agonists have different chemical structures, making it difficult to construct a pharmacophore model that takes them all into account. Here we propose a new three-dimensional pharmacophore model that encompasses the kappa-activities of all classes, which utilizes conformational sampling of agonists by high-temperature molecular dynamics and pharmacophore extraction through a series of molecular superpositions.
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