Opioids indole derivative

Incapacitation produced by less likely candidates such as LSD and other indole derivatives, psychedelic phenethylamines, and potent opioids is theoretically possible, but it is unlikely that any of these compounds would be employed militarily. Covert use, which is logistically easier to accomplish and has fewer constraints, opens a broader spectrum of possibilities. This, however, is a concept that involves considerations that generally extend beyond the scope of chemical warfare. 

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 C-3 substituted derivatives 154-160 were prepared from the corresponding naltrexone by Fischer indoliza-tion (PhNHNH -HCl, p-TSA, EtOH, reflux 22%-72%). Of these indoles, although only 154 shows comparable selectivity with naltrindole for the 8-opioid receptor, none of these analogues 154-160 possess acceptable affinity for this receptor [339], Indolomorphinan 161 is a 8-opioid receptor antagonist (K=0.7 nM) and has good 8... 

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