title: Selective kappa-opioid antagonists related to naltrindole. Effect of side-chain spacer in the 5'-amidinoalkyl series.
abstract: The study of kappa-opioid receptor function in vivo has been hampered by the limited choice of selective kappa-antagonists. Recently discovered kappa-antagonists have not yet been utilised in vivo. We here report the synthesis and in vitro evaluation of a new amidine derivative of naltrindole. It showed substantially greater kappa-selectivity in binding assays than known analogues with shorter spacer in the amidine side chain. This indicates that in nor-BNI and related selective kappa-antagonists, the second basic centre may not be ideally located.
authors.affiliation: School of Chemistry, University of Bristol, UK.
authors.forename: A R
authors.initials: AR
authors.lastname: Jales
authors.forename: S M
authors.initials: SM
authors.lastname: Husbands
authors.forename: J W
authors.initials: JW
authors.lastname: Lewis
mesh_terms: D000578:Amidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D044482:Benzeneacetamides; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D015195:Drug Design; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000493:pharmacokinetics; D020881:Enkephalin, D-Penicillamine (2,5)- / Q000493:pharmacokinetics; D006168:Guinea Pigs; D007202:Indicators and Reagents; D007700:Kinetics; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011759:Pyrrolidines / Q000493:pharmacokinetics; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D000578:Amidines; D044482:Benzeneacetamides; D007202:Indicators and Reagents; D009292:Narcotic Antagonists; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009271:Naltrexone; D020881:Enkephalin, D-Penicillamine (2,5)-; C055382:naltrindole; C045444:U 69593