Synthesis and biological activity of 3-substituted 3-desoxynaltrindole derivatives

H Kubota; R B Rothman; C Dersch; K McCullough; J Pinto; K C Rice

doi:10.1016/s0960-894x(98)00105-x

Synthesis and biological activity of 3-substituted 3-desoxynaltrindole derivatives

Bioorg Med Chem Lett. 1998 Apr 7;8(7):799-804. doi: 10.1016/s0960-894x(98)00105-x.

Authors

H Kubota¹, R B Rothman, C Dersch, K McCullough, J Pinto, K C Rice

Affiliation

¹ Laboratory of Medicinal Chemistry, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

PMID: 9871544
DOI: 10.1016/s0960-894x(98)00105-x

Abstract

The 3-unsubstituted and substituted analogs of naltrindole (NTI) were synthesized using palladium-catalyzed transformations, and their binding affinity to opioid receptors was determined. Although the 3-desoxy analog showed comparable delta selectivity with that of NTI, all of the novel compounds possessed low affinity for delta receptors indicating the important role of the 3-oxygen atom of NTI for interaction with delta-opioid receptors.

MeSH terms

Animals
Benzeneacetamides*
Binding, Competitive
Brain / metabolism
Cell Membrane / metabolism
Drug Design
Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
Enkephalin, Leucine-2-Alanine / metabolism
Enkephalins / metabolism
Molecular Structure
Naltrexone / analogs & derivatives*
Naltrexone / chemical synthesis*
Naltrexone / chemistry
Naltrexone / pharmacology
Narcotic Antagonists / chemical synthesis*
Narcotic Antagonists / chemistry
Narcotic Antagonists / pharmacology
Pyrrolidines / metabolism
Rats
Receptors, Opioid, delta / drug effects
Receptors, Opioid, delta / metabolism
Structure-Activity Relationship

Substances

Benzeneacetamides
Enkephalins
Narcotic Antagonists
Pyrrolidines
Receptors, Opioid, delta
Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
Naltrexone
Enkephalin, Leucine-2-Alanine
naltrindole
U 69593