Studies on analgesic agents. 1. Preparation of 1,2-diphenyl-2-(4-substituted 1-piperazinyl)ethanol derivatives and structure-activity relationships

Abstract

The preparation and analgesic activity of a series of the title compounds (8-55 and 57) are described. The intermediates, 2-phenyl-2-(1-piperazinyl)acetophenones 5 and 6, were prepared from benzyl phenyl ketones 3 via their bromides 4. On reduction, compounds 5 afforded the titled compounds 8-12, 16, and 26-48. Compounds 13-15 and 17-25 were obtained by alkylation or benzylation of 1.2-diphenyl-2-(1-piperazinyl)ethanols 7 derived from 6 by reduction. The reduction of 5 and 6 with metal hydrides predominantly gave the erythro isomers. The erythro isomers were remarkably more active than their threo isomers. The more active members in this series of compounds were 16 and derivatives 35 and 37-44 of dl-erythro-1-phenyl-2-(substituted phenyl)-2-[4-(p-methoxybenzyl)-1-piperazinyl]ethanol. Compounds 16, 43, and 44 were the most active with a potency of about two to three times that of codeine. Racemates 16 and 38 were resolved into their optical isomers and it was found that (-)-16 and (+)-38 were more potent than their antipodes. Structure-activity relationship are discussed.

Report on a New Opioid NPS: Chemical and In Vitro Functional Characterization of a Structural Isomer of the MT-45 Derivative Diphenpipenol

“…Extensive NMR analysis showed that the product obtained was a structural isomer of diphenpipenol (the difference lies in the position of the hydroxyl group, Figure 1). This isomer has up to now only been mentioned once in literature (14), and no information on the potency of this compound has been reported before.…”

Synthesis of 2-(methylsulfonyl)-5-(4-(methylsulfonyl) phenyl)-4-phenyl-1H-[5-14C]imidazole, a selective COX-2 inhibitor, via asymmetrical benzoins

“…The product 5 was hydrolyzed under acidic conditions to 2‐phenyl[1‐ 14 C]acetic acid 6 . By reaction between methyl phenyl sulfide 7 and 6 in the presence of phosphoric acid and trifluoroacetic anhydride produced compound 1‐(4‐(methylthio)phenyl)‐2‐phenyl[1‐ 14 C]ethanone 8 . Compound 8 was treated with bromine in acetic acid as solvent to give 2‐bromo‐1‐(4‐(methylthio)phenyl)‐2‐phenyl[1‐ 14 C]ethanone 9 .…”

Synthesis, spectral studies and biological evaluation of a novel series of 2-substituted-5,6-diarylsubstituted imidazo(2,1-b)-1,3,4-thiadiazole derivatives as possible anti-tubercular agents

“…Subsequently, 3a-e were subjected to bromination using liquid bromine in chloroform to obtain a-bromo-1, 2-(p-substituted)diaryl-1-ethanones 4a-e as shown in Scheme 1 (Veeramaneni et al, 2003;Shimokawa et al, 1979).…”