Naltrindoles

Fig. 4. Structures of several nonpeptide opioid agonists, (a) morphine, (c) BW373U86, (e) U50488 and antagonists, (b) naloxone, (d) naltrindole, and (f)...

FIGURE 9.19 Dimeric antagonist formed by oligoglycyl-based linkage of two opioid receptor subtype antagonists naltrindole and ICI-199,441. From [59],... 

Selective antagonists (naloxone) CTAP Naltrindole Nor-binaltorphimine J-113 397... 

Antagonists Naloxone Beta ENA Naloxone Naltrindole Naloxone Not BNI Not naloxone... 

Portoghese PS, Nagase H, Maloney Huss KE, Lin CE, Takemori AE. Role of spacer and address components in peptidomimetic 6 opioid receptor antagonists related to naltrindole. J Med Chem 1991 34 1715-1720. 

Sofuoglu M, Portoghese P, Takemori A. Differential antagonism of delta opioid agonists by naltrindole and its benzofuran analog (NTB) in mice evidence for delta opioid receptor subtypes. 

DPDPE—D-Pen2, D-Pen5-enkephalin DSLET—D-Ser2, Leu5-enkephalin, Thr6 DYN—Dynorphin EM—endomorphin ENK— enkephalin j8-FNA—j8-funaltrexamine, NTH—naltrindole 5 -isothiocyanate nor-BNI—Nor-binaltorphimine. 

Portoghese and coworkers also considered other naltrindole derivatives substituted in position 6 or 7 with aryl, benzyl or aniline moieties to evaluate the effect of flexible aryl groups on selectivity, but obtained non-selective compounds only. This result demonstrates that the conformational flexibility of these aryl groups causes them to reside preferentially in regions of space that are not accepted by the 8 opioid receptor (Portoghese et al., 1994). A more rigid compound however, 7-benzylidene-naltrindole (BNTX) proved to be a potent and highly... 

Jiang, Q., Takemori, A.E., Sultana, M., etal. Differential antagonism of opioid delta antinociception by [D-Ala2,Leu5,Cys6]enkephalin and naltrindole 5 -isothiocyanate evidence for delta receptor subtypes, J. Pharmacol. Exp.Ther. 1991, 257, 1069-1095. 

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