Biomaterial Database

Electrophilic N-benzylnaltrindoles as delta opioid receptor-selective antagonists. 1995

V L Korlipara, and A E Takemori, and P S Portoghese

Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota, Minneapolis 55455, USA.

The N-benzyl group of N-benzylnaltrindole (1, BNTI), a potent and selective delta 2 opioid receptor antagonist, was employed as a scaffold to hold electrophilic moieties (isothiocyanate and haloacetamide) in an effort to obtain selective affinity labels (2-4 and 8-11). The corresponding acetamide derivatives (5-7) also were synthesized to serve as nonelectrophilic controls. The o- and p-isothiocyanates (2 and 4) and the haloamides (8-11) were selective delta opioid receptor antagonists in the mouse vas deferens (MVD) preparations, while the meta isomer 3 was a delta-selective full agonist (IC50 = 5 nM). The fact that the effect of 2 and 4 was found to increase as a function of time in MVD suggests a covalent mechanism for the wash resistant component. The m-isothiocyanate 3 was found to be a delta-selective and irreversible agonist in the MVD, and it is suggested that it may be covalently binding to an agonist recognition site. In the mouse abdominal stretch antinociceptive assay, compounds 2-4 and 9 were delta-selective antagonists but exhibited delta 2/delta 1 selectivity ratios than that of BNTI.

UI	MeSH Term	Description	Entries
D007082	Ileum	The distal and narrowest portion of the SMALL INTESTINE, between the JEJUNUM and the ILEOCECAL VALVE of the LARGE INTESTINE.
D008297	Male		Males
D009130	Muscle, Smooth	Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. (From Stedman, 25th ed)	Muscle, Involuntary,Smooth Muscle,Involuntary Muscle,Involuntary Muscles,Muscles, Involuntary,Muscles, Smooth,Smooth Muscles
D009271	Naltrexone	Derivative of noroxymorphone that is the N-cyclopropylmethyl congener of NALOXONE. It is a narcotic antagonist that is effective orally, longer lasting and more potent than naloxone, and has been proposed for the treatment of heroin addiction. The FDA has approved naltrexone for the treatment of alcohol dependence.	Antaxone,Celupan,EN-1639A,Nalorex,Naltrexone Hydrochloride,Nemexin,ReVia,Trexan,EN 1639A,EN1639A
D011869	Radioligand Assay	Quantitative determination of receptor (binding) proteins in body fluids or tissue using radioactively labeled binding reagents (e.g., antibodies, intracellular receptors, plasma binders).	Protein-Binding Radioassay,Radioreceptor Assay,Assay, Radioligand,Assay, Radioreceptor,Assays, Radioligand,Assays, Radioreceptor,Protein Binding Radioassay,Protein-Binding Radioassays,Radioassay, Protein-Binding,Radioassays, Protein-Binding,Radioligand Assays,Radioreceptor Assays
D001921	Brain	The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.	Encephalon
D006168	Guinea Pigs	A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.	Cavia,Cavia porcellus,Guinea Pig,Pig, Guinea,Pigs, Guinea
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D014649	Vas Deferens	The excretory duct of the testes that carries SPERMATOZOA. It rises from the SCROTUM and joins the SEMINAL VESICLES to form the ejaculatory duct.	Ductus Deferens,Deferens, Ductus,Deferens, Vas
D015394	Molecular Structure	The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds.	Structure, Molecular,Molecular Structures,Structures, Molecular