1-Substituted 4-(1,2-diphenylethyl)piperazine derivatives and their analgesic activities. 1

Abstract

The preparation and analgesic activities of a series of the entitled compounds (5-22) and the optical isomers of the 1-cyclohexyl derivative 5 are described. Reactions of N,N-bis(2-chloroethyl)-1,2-diphenylethylamine (3) with ammonia and primary amines gave N-(1,2-diphenylethyl)piperazine (4) and N1-substituted derivatives (5-20, 22), respectively. The alkylation of 4 afforded 12-21. Compounds 5-18 and 22 were also obtained by the reactions of 1,2-diphenylethylamine (23) and N-substituted 2,2'-dichlorodiethylamine. Racemate 5 was resolved with (+)- or (-)-2'-nitrotartranilic acid into its optical isomers [(+)-5 and (-)-5], and the absolute configuration of (+)-5 was determined to be S configuration by the synthesis and optical rotatory dispersion measurements. The most active members in this series of compounds were 5-7, which were approximately as potent as (-)-morphine. In the case of 5, the more potent enantiomer (S)-(+)-5 has the opposite configuration to that of (-)-N,N-dimethyl-1,2-diphenylethylamine (Spa) or (-)-morphine with respect to the (C-9) asymmetric center and belongs to a new series of compounds having potent analgesic activity.

Changes in the prevalence of new psychoactive substances before and after the introduction of the generic scheduling of synthetic cannabinoids in Japan

“…25I-NBOMe and 25C-NBOMe) and stimulant thiophene analogs (e.g. [42][43][44][45][46] These designer drugs were detected together with several synthetic cannabinoids and cathinone derivatives in the products. [29,34] AH-7921 and MT-45 also emerged as new types of designer drugs.…”

Test purchase, synthesis, and characterization of 2‐methoxydiphenidine (MXP) and differentiation from its meta‐ and para‐substituted isomers

“…The 1,2‐diphenylethylamine structural template provides access to a range of substances with various properties including bronchodilation and analgesic activity . The synthetic opioid analgesic 1‐cyclohexyl‐4‐(1,2‐diphenylethyl)piperazines (MT‐45, Figure A) has also been encountered as a ‘research chemical’ and ‘legal opioid’.…”

“…The 1,2-diphenylethylamine structural template provides access to a range of substances with various properties including bronchodilation [8] and analgesic activity. [9,10] The synthetic opioid analgesic 1-cyclohexyl-4-(1,2-diphenylethyl)piperazines (MT-45, Figure 1A) has also been encountered as a 'research chemical' and 'legal opioid'. It has recently been associated with a range of fatal and non-fatal intoxications, which led to a risk assessment procedure that was carried out under the auspices of the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA).…”

Alopecia and Associated Toxic Agents: A Systematic Review

“…MT-45, a synthetic opioid invented in the 1970s, was originally developed as an opioid analgesic, with activity comparable to that of morphine [54, 55]. Sold on the internet as “research chemicals,” MT-45 and other synthetic opioids have recently been implicated in multiple fatalities.…”