Design, synthesis, and biological evaluation of 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-[(4'-pyridyl)carboxamido]morphinan derivatives as peripheral selective μ opioid receptor Agents.
作者： Yunyun Yuan , Orgil Elbegdorj , Jianyang Chen , Shashidhar K. Akubathini , Feng Zhang
DOI: 10.1021/JM301247N
关键词:
摘要: Peripheral selective μ opioid receptor (MOR) antagonists could alleviate the symptoms of opioid-induced constipation (OIC) without compromising analgesic effect opioids. However, a variety adverse effects were associated with them, partially due to their relatively low MOR selectivity. NAP, 6β-N-4′-pyridyl substituted naltrexamine derivative, was identified previously as potent and highly antagonist mainly acting within peripheral nervous system. The noticeable diarrhea it prompted design synthesis its analogues in order study structure–activity relationship. Among compound 8 showed improved pharmacological profiles compared original lead, at while increasing intestinal motility morphine-pelleted mice (ED50 = 0.03 mg/kg). slight decrease ED50 lead well compensated by unobserved effect. Hence, this seems be more promising de...
acs.org
sci-hub.se 参考文章(71)
Rao S. Rapaka, Frank Porreca, Development of delta opioid peptides as nonaddicting analgesics. Pharmaceutical Research. ,vol. 8, pp. 1- 8 ,(1991) , 10.1023/A:1015809702296
S. F. COOK, L. LANZA, X. ZHOU, C. T. SWEENEY, D. GOSS, K. HOLLIS, A. W. MANGEL, S. E. FEHNEL, Gastrointestinal side effects in chronic opioid users: results from a population-based survey Alimentary Pharmacology & Therapeutics. ,vol. 27, pp. 1224- 1232 ,(2008) , 10.1111/J.1365-2036.2008.03689.X
J.S. McKay, B.D. Linaker, N.B. Higgs, L.A. Turnberg, Studies of the antisecretory activity of morphine in rabbit ileum in vitro. Gastroenterology. ,vol. 82, pp. 243- 247 ,(1982) , 10.1016/0016-5085(82)90011-7
Janet Yancey-Wrona, Brian Dallaire, Edward Bilsky, Brad Bath, John Burkart, Lynn Webster, Dan Magiera, Xiaoxia Yang, Mitch Phelps, Wolfgang Sadee, 6β‐Naltrexol, a Peripherally Selective Opioid Antagonist that Inhibits Morphine‐Induced Slowing of Gastrointestinal Transit: An Exploratory Study Pain Medicine. ,vol. 12, pp. 1727- 1737 ,(2011) , 10.1111/J.1526-4637.2011.01279.X
A Tavani, G Bianchi, L Manara, P Ferretti, Inhibition of gastrointestinal transit by morphine in rats results primarily from direct drug action on gut opioid sites. Journal of Pharmacology and Experimental Therapeutics. ,vol. 237, pp. 945- 949 ,(1986)
T F Burks, J J Galligan, Centrally mediated inhibition of small intestinal transit and motility by morphine in the rat. Journal of Pharmacology and Experimental Therapeutics. ,vol. 226, pp. 356- 361 ,(1983)
Stefan Mueller-Lissner, Fixed Combination of Oxycodone with Naloxone: a New Way to Prevent and Treat Opioid-induced Constipation Advances in Therapy. ,vol. 27, pp. 581- 590 ,(2010) , 10.1007/S12325-010-0057-Y
Saeed Esmaeili-Mahani, Mohammad Javan, Fereshteh Motamedi, Abolhasan Ahmadiani, Post-adrenalectomy changes in the gene expression of specific G-protein subunits involved in morphine sensitization. Neuropeptides. ,vol. 42, pp. 169- 175 ,(2008) , 10.1016/J.NPEP.2007.12.002
I. D. Jeong, M. Camilleri, A. Shin, J. Iturrino, A. Boldingh, I. Busciglio, D. Burton, M. Ryks, D. Rhoten, A. R. Zinsmeister, A randomised, placebo-controlled trial comparing the effects of tapentadol and oxycodone on gastrointestinal and colonic transit in healthy humans Alimentary Pharmacology & Therapeutics. ,vol. 35, pp. 1088- 1096 ,(2012) , 10.1111/J.1365-2036.2012.05040.X
Peter Holzer, Opioid antagonists for prevention and treatment of opioid-induced gastrointestinal effects. Current Opinion in Anesthesiology. ,vol. 23, pp. 616- 622 ,(2010) , 10.1097/ACO.0B013E32833C3473