title: Synthesis and biological evaluation of some 6-arylamidomorphines as analogues of morphine-6-glucuronide.
abstract: A series of 6-beta-arylamidomorphines was synthesized and biologically evaluated. Various aryl substituents were introduced into the arylamidomorphines to examine substituent structure-activity relationships. Competition binding assays showed that compounds 10a-h bound to the mu opioid receptor with high affinity (0.2-0.6 nM). Functional assays showed that compounds 10a-h acted as full mu opioid receptor agonists. The ED(50) of compound 10e.HCl as an analgesic was 12.6 mg/kg in the tail flick latency test in the rat.
authors.affiliation: Human BioMolecular Research Institute, 5310 Eastgate Mall, San Diego, CA 92121-2804, USA. jmacdougall@hbri.org
authors.forename: James M
authors.initials: JM
authors.lastname: Macdougall
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Zhang
authors.forename: Willma E
authors.initials: WE
authors.lastname: Polgar
authors.forename: Taline V
authors.initials: TV
authors.lastname: Khroyan
authors.forename: Lawrence
authors.initials: L
authors.lastname: Toll
authors.forename: John R
authors.initials: JR
authors.lastname: Cashman
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D009022:Morphine Derivatives / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology
chemical_list: D009022:Morphine Derivatives; C035349:morphine-6-glucuronide; D009020:Morphine