125190-67-2Relevant academic research and scientific papers
Synthesis and evaluation of novel peripherally restricted κ-opioid receptor agonists
Kumar, Virendra,Guo, Deqi,Cassel, Joel A.,Daubert, Jeffrey D.,DeHaven, Robert N.,DeHaven-Hudkins, Diane L.,Gauntner, Erin K.,Gottshall, Susan L.,Greiner, Susan L.,Koblish, Michael,Little, Patrick J.,Mansson, Erik,Maycock, Alan L.
, p. 1091 - 1095 (2007/10/03)
A series of 3-substituted analogs (3) of the parent κ agonist, 1, were prepared to limit access to the central nervous system. With the exception of compound 3j, all other compounds bound to the human κ opioid receptor with high affinity (Ki =
Structure/Activity Studies Related to 2-(3,4-Dichlorophenyl)-N-methyl-N-acetamides: A Novel Series of Potent and Selective κ-Opioid Agonists
Barlow, Jeffrey J.,Blackburn, Thomas P.,Costello, Gerard F.,James, Roger,Count, David J. Le,et al.
, p. 3149 - 3158 (2007/10/02)
This paper describes the synthesis of a series of N-acetamides 1, variously substituted at the carbon adjacent to the amide nitrogen (C1), and related analogues, together with their biological evaluation as opioid κ agonists.In the first part of the study, the variants in N-acyl, N-alkyl, and amino functions were explored when the substituent at C1 was 1-methylethyl and the optimum was found to be exemplified by 2-(3,4-dichlorophenyl)-N-methyl-N-acetamide (13).Subsequently, racemic or chiral amino acids were used to introduce other alkyl and aryl substituents at C1 of the ethyl linking moiety.A series of potent compounds, bearing substituted-aryl groups at C1, were discovered, typified by 2-(3,4-dichlorophenyl)-N-methyl-N-acetamide (48), which was 5-fold more active as the racemate than 13 in vitro and exhibited potent naloxone-reversible analgesic effects (ED50 = 0.04 mg/kg sc) in a mouse abdominal constriction model.
