Syntheses of novel high affinity ligands for opioid receptors |
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Authors: | Mark P. Wentland Rongliang Lou Qun Lu Yigong Bu Christoph Denhardt Jin Jin Rakesh Ganorkar Melissa A. VanAlstine Chengyun Guo Dana J. Cohen Jean M. Bidlack |
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Affiliation: | 1. Department of Chemistry and Chemical Biology, Rensselaer Polytechnic Institute, Troy, NY 12180, USA;2. Pharmaceutical Chemistry, Alkermes, Inc., Cambridge, MA 02139, USA;3. Department of Pharmacology and Physiology, School of Medicine and Dentistry, University of Rochester, Rochester, NY 14642, USA |
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Abstract: | A series of novel high affinity opioid receptor ligands have been made whereby the phenolic-OH group of nalbuphine, naltrexone methiodide, 6-desoxonaltrexone, hydromorphone and naltrindole was replaced by a carboxamido group and the furan ring was opened to the corresponding 4-OH derivatives. These furan ring ‘open’ derivatives display very high affinity for μ and κ receptors and much less affinity for δ. The observation that these target compounds have much higher receptor affinity than the corresponding ring ‘closed’ carboxamides significantly strengthens our underlying pharmacophore hypothesis concerning the bioactive conformation of the carboxamide group. |
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