Design, synthesis, and characterization of 6β-naltrexol analogs, and their selectivity for in vitro opioid receptor subtypes
作者： Andrea L. Pelotte , Ryan M. Smith , Mario Ayestas , Christina M. Dersch , Edward J. Bilsky
DOI: 10.1016/J.BMCL.2009.03.095
关键词: In vivo 、 Receptor 、 Opioid receptor 、 Alkaloid 、 μ-opioid receptor 、 Biological activity 、 Chemical synthesis 、 Stereochemistry 、 Opioid 、 Chemistry
摘要: Since the mu opioid receptor (MOR) is known to be involved in therapeutically relevant pathways leading manifestation of pain and addiction, we are currently studying specific structural characteristics that promote antagonism at MOR. The opiates 6beta-naltrexol 6beta-naltrexamide function as neutral antagonists vitro vivo systems previously exposed morphine, under investigation improved treatments for narcotic dependence. In this research, synthesized characterized carbamate sulfonate ester derivates do not contain a protic group C(6), evaluated these compounds affinity. subtype (mu, kappa, delta receptors) binding data derivatives reported. All four exhibited affinity MOR better than standard HCl. Based on K(i) data, order follows: 9>13>14>10>6beta-naltrexol Carbamate 9 tosylate 13 displayed subnanomolar MOR, while 10 was most mu-selective compound synthesized. conclusion, our indicate absence hydrogen-bond donor C(6) oxygen enhances rather impedes naltrexol Additionally, also suggest increasing bulk around may allow control selectivity within series.
maine.edu
elsevier.com
sci-hub.se 参考文章(28)
Protection for Phenols and Catechols John Wiley & Sons, Inc.. pp. 246- 292 ,(2002) , 10.1002/9780470053485.CH3
Danxin Wang, Kirsten M. Raehal, Edward J. Bilsky, Wolfgang Sadée, Inverse agonists and neutral antagonists at mu opioid receptor (MOR): possible role of basal receptor signaling in narcotic dependence. Journal of Neurochemistry. ,vol. 77, pp. 1590- 1600 ,(2001) , 10.1046/J.1471-4159.2001.00362.X
Gertrud Andersen, Lona Christrup, Per Sjøgren, Relationships Among Morphine Metabolism, Pain and Side Effects During Long-Term Treatment: An Update Journal of Pain and Symptom Management. ,vol. 25, pp. 74- 91 ,(2003) , 10.1016/S0885-3924(02)00531-6
Danxin Wang, Kirsten M. Raehal, Emil T. Lin, John J. Lowery, Brigitte L. Kieffer, Edward J. Bilsky, Wolfgang Sadée, Basal Signaling Activity of μ Opioid Receptor in Mouse Brain: Role in Narcotic Dependence Journal of Pharmacology and Experimental Therapeutics. ,vol. 308, pp. 512- 520 ,(2004) , 10.1124/JPET.103.054049
Zaijie Wang, Edward J. Bilsky, Frank Porreca, Wolfgang Sadée, Accelerated communciation: Constitutive μ opioid receptor activation as a regulatory mechanism underlying narcotic tolerance and dependence Life Sciences. ,vol. 54, ,(1994) , 10.1016/0024-3205(94)90022-1
Sinead Donnelly, Mellar P. Davis, Declan Walsh, Michael Naughton, Morphine in cancer pain management: a practical guide. Supportive Care in Cancer. ,vol. 10, pp. 13- 35 ,(2002) , 10.1007/S005200100274
Sandra Comer, Eric Collins, Herbert Kleber, Elie Nuwayser, James Kerrigan, Marian Fischman, Depot naltrexone: long-lasting antagonism of the effects of heroin in humans Psychopharmacology. ,vol. 159, pp. 351- 360 ,(2002) , 10.1007/S002130100909
M Narita, Regulations of opioid dependence by opioid receptor types Pharmacology & Therapeutics. ,vol. 89, pp. 1- 15 ,(2001) , 10.1016/S0163-7258(00)00099-1
Kirsten M. Raehal, John J. Lowery, Castigliano M. Bhamidipati, Ryan M. Paolino, Jennifer R. Blair, Danxin Wang, Wolfgang Sadée, Edward J. Bilsky, In Vivo Characterization of 6β-Naltrexol, an Opioid Ligand with Less Inverse Agonist Activity Compared with Naltrexone and Naloxone in Opioid-Dependent Mice Journal of Pharmacology and Experimental Therapeutics. ,vol. 313, pp. 1150- 1162 ,(2005) , 10.1124/JPET.104.082966
L. LaSalle, G. Rachelska, B. Nedelec, Naltrexone for the management of post-burn pruritus: A preliminary report Burns. ,vol. 34, pp. 797- 802 ,(2008) , 10.1016/J.BURNS.2007.10.009