2,8-Bis(substituted amino)phenothiazine 5,5-Dioxides¹

3-(αR)-α-((2S,5R)-4-Allyl-2,5-dimethyl-1-piperazinyl)-3-hydroxybenzyl)- N-alkyl-N-arylbenzamides: Potent, Non-Peptidic Agonists of Both the μ and δ Opioid Receptors

“…While there were small differences in potency between the analogues with substituents on the phenyl ring, no small substituent caused a significant loss of either µ or δ opioid activity. Further examples include the o-trifluoromethyl (27), p-methoxy (28), and p-nitroaniline (29) analogues, all of which were tolerated by both receptors, with compound 28 slightly more potent at δ and µ than 27 and 29.…”

“…26 Similarly, N-ethyl, Npropyl, and N-butyl compounds were prepared by acylation of the aniline followed by borane reduction of the amide. 27 N-Cyclopropylaniline was prepared from cyclopropylamine via adaptation of Barton's phenylation procedure using triphenylbismuth and copper acetate. 28 All of these anilines reacted readily with acid chloride 6 in the presence of triethylamine to produce, after deprotection of the phenol using tetraethylammonium fluoride, the desired targets.…”

“…N -Methyl compounds were prepared by N-formylation of the appropriate aniline using the mixed anhydride method (acetic/formic anhydride), followed by borane/dimethyl sulfide reduction to the N -methylaniline . Similarly, N -ethyl, N -propyl, and N -butyl compounds were prepared by acylation of the aniline followed by borane reduction of the amide …”