Guanidino N-substituted and N,N-disubstituted derivatives of the kappa-opioid antagonist GNTI

Shannon L Black; Cedric Chauvignac; Peter Grundt; Carl N Miller; Susan Wood; John R Traynor; John W Lewis; Stephen M Husbands

doi:10.1021/jm0309203

Guanidino N-substituted and N,N-disubstituted derivatives of the kappa-opioid antagonist GNTI

J Med Chem. 2003 Dec 4;46(25):5505-11. doi: 10.1021/jm0309203.

Authors

Shannon L Black¹, Cedric Chauvignac, Peter Grundt, Carl N Miller, Susan Wood, John R Traynor, John W Lewis, Stephen M Husbands

Affiliation

¹ Department of Pharmacy and Pharmacology, University of Bath, Bath, BA2 7AY, UK.

PMID: 14640558
DOI: 10.1021/jm0309203

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.

Publication types

Research Support, U.S. Gov't, P.H.S.

MeSH terms

Animals
CHO Cells
Cricetinae
Guanidines / chemical synthesis*
Guanidines / chemistry
Guanidines / pharmacology
Humans
Morphinans / chemical synthesis*
Morphinans / chemistry
Morphinans / pharmacology
Receptors, Opioid, kappa / antagonists & inhibitors*
Structure-Activity Relationship

Substances

17-cyclopropylmethyl-6,7-didehydro-4,5-epoxy-5'-guanidinyl-3,14-dihydroxyindolo(2',3'-6,7)morphinan
Guanidines
Morphinans
Receptors, Opioid, kappa

Abstract

Publication types

MeSH terms

Substances

Grants and funding