development of 5-substituted n-methylmorphinan-6-ones as potent opioid analgesics with improved side-effect profile发展5-substituted n-methylmorphinan-6-ones与改进的强效阿片类止痛药的副作用.pdfVIP

Hindawi Publishing Corporation International Journal of Medicinal Chemistry Volume 2012, Article ID 208039, 10 pages doi:10.1155/2012/208039 Review Article Development of 5-Substituted N -Methylmorphinan-6-ones as Potent Opioid Analgesics with Improved Side-Effect Profile Helmut Schmidhammer and Mariana Spetea Department of Pharmaceutical Chemistry, Institute of Pharmacy and Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Innrain 52a, 6020 Innsbruck, Austria Correspondence should be addressed to Helmut Schmidhammer, helmut.schmidhammer@uibk.ac.at Received 3 February 2012; Accepted 4 April 2012 Academic Editor: Severo Salvadori Copyright © 2012 H. Schmidhammer and M. Spetea. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. One of the most important functions of the opioid system is the control of pain. Among the three main opioid receptor classes (μ, δ, κ), the μ (MOR) is the main type targeted for pharmacotherapy of pain. Opioid analgesics such as morphine, oxycodone and fentanyl are agonists at the MOR and are the mainstay for the treatment of moderate-to-severe pain. However, adverse effects related to opioid use are severe and often lead to early discontinuation and inadequate analgesia. The development of more effective and safer medications for the management of pain still remains a major direction in pharmaceutical research. Chemical approaches towards the identification of novel MOR analgesics with reduced side effects include structural modifications of 14-alkoxy-N - methylmorphinan-6-ones in key positions that are important for binding, selectivity, potency, and effic