Naltrindole derivative

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... 

Both peptide and nonpeptide 5-opioid antagonists have been developed. The nonpeptide 6-antagonist naltrindole and its analogues are described in Chapter 9 of this volume. In the present chapter, the development of opioid peptide-derived 6-antagonists, inverse 6-agonists, and mixed p-agonist/6-antagonists is reviewed. 

Fluorescent derivatives of naltrindole have been prepared. The fluorescent analog in which fluorescein was attached through a tet-raglycine spacer to 7 -amino-NTI has been prepared (339) its fluorescence is blocked by NTI, indicating specific binding to 8 receptors. Recently, a fluorogenic "reporter affinity label" derivative of naltrindole, PNTI, was prepared from 7 -amino-NTI that, in contrast to its reversible counterpart, is an agonist in the MVD (340) (see Section 5.11 below). 

The aromatic ring in the "address" portion of naltrindole and its analogs is important for antagonist activity at 8 receptors. The tetra-hydroindole derivate is much less potent, as are several 6-aryl derivatives (195). The 7(.E)-benzylidine analog of naltrexone, 7-benzyli-denenaltrexone (BNTX, 44, Fig. 7.8), however, is a potent 8 antagonist (193,342). It has... 

Opioid receptor binding data have been reported for a series of 17-cyclopropyl-methylnoraminomorphindole derivatives (59, Fig. 13) [56]. All but the propyla-mino derivative (59b) had subnanomolar affinity for DOR which reduced its DOR selectivity compared with ethylamino- (59a) which was the only new ligand comparable in selectivity with naltrindole (58b). The indolic-substituted formyla-mino- derivatives were investigated as potential PET ligands for imaging studies of DOR. Alkylation of the indolic /V-atom allowed retention of high affinity for DOR. The fluoroethyl substituent (59d) had little effect on selectivity but fluoropropyl (59e) lowered selectivity. 

The phenolic group in naltrindole can be deoxygenated via the derived triflate by treat-... 

---