title: Guanidino N-substituted and N,N-disubstituted derivatives of the kappa-opioid antagonist GNTI.
abstract: Derivatives of the highly selective kappa-opioid receptor antagonist GNTI (2a) have been prepared. Binding and functional studies conducted on cloned human opioid receptors expressed in Chinese hamster ovarian (CHO) cells suggested that adding a benzyl or a substituted benzyl group to the guanidino moiety led, in general, to a retention of high kappa-affinity and antagonist potency. Disubstitution of the guanidino moiety led to reduced kappa-selectivity.
authors.affiliation: Department of Pharmacy and Pharmacology, University of Bath, Bath, BA2 7AY, UK.
authors.forename: Shannon L
authors.initials: SL
authors.lastname: Black
authors.forename: Cedric
authors.initials: C
authors.lastname: Chauvignac
authors.forename: Peter
authors.initials: P
authors.lastname: Grundt
authors.forename: Carl N
authors.initials: CN
authors.lastname: Miller
authors.forename: Susan
authors.initials: S
authors.lastname: Wood
authors.forename: John R
authors.initials: JR
authors.lastname: Traynor
authors.forename: John W
authors.initials: JW
authors.lastname: Lewis
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Husbands
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D006146:Guanidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D009019:Morphinans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: C411465:17-cyclopropylmethyl-6,7-didehydro-4,5-epoxy-5'-guanidinyl-3,14-dihydroxyindolo(2',3'-6,7)morphinan; D006146:Guanidines; D009019:Morphinans; D017473:Receptors, Opioid, kappa