Guanidino N-substituted and N,N-disubstituted derivatives of the kappa-opioid antagonist GNTI.
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.
Black
Shannon L
SL
Department of Pharmacy and Pharmacology, University of Bath, Bath, BA2 7AY, UK.
Chauvignac
Cedric
C
Grundt
Peter
P
Miller
Carl N
CN
Wood
Susan
S
Traynor
John R
JR
Lewis
John W
JW
Husbands
Stephen M
SM
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
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