62755-64-0Relevant academic research and scientific papers
BIPHENYL DERIVATIVES, PHARMACEUTICAL COMPOSITION COMPRISING THE SAME, AND PREPARATION METHOD THEREOF
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, (2014/08/19)
Provided are biphenyl derivatives exhibiting activity towards central nervous system diseases by acting on the 5-HT7 receptor, pharmaceutically acceptable salts thereof, a method for preparing the compounds and pharmaceutical compositions inclu
Discovery and pharmacological characterization of aryl piperazine and piperidine ethers as dual acting norepinephrine reuptake inhibitors and 5-HT1A partial agonists
Gray, David L.,Xu, Wenjian,Campbell, Brian M.,Dounay, Amy B.,Barta, Nancy,Boroski, Susan,Denny, Lynne,Evans, Lori,Stratman, Nancy,Probert, Al
scheme or table, p. 6604 - 6607 (2010/06/12)
Compounds that are both norepinephrine reuptake inhibitors (NRI) and 5-HT1A partial agonists may have the potential to treat neuropsychiatric disorders including attention deficit hyperactivity disorder (ADHD) and depression. Targeted screening
Synthesis and Structure-Activity Relationships of Novel Arylpiperazines as Potent and Selective Agonists of the Melanocortin Subtype-4 Receptor
Richardson, Timothy I.,Ornstein, Paul L.,Briner, Karin,Fisher, Matthew J.,Backer, Ryan T.,Biggers, C. Kelly,Clay, Michael P.,Emmerson, Paul J.,Hertel, Larry W.,Hsiung, Hansen M.,Husain, Saba,Kahl, Steven D.,Lee, Jonathan A.,Lindstrom, Terry D.,Martinelli, Michael J.,Mayer, John P.,Mullaney, Jeffery T.,O'Brien, Thomas P.,Pawlak, Joseph M.,Revell, Kevin D.,Shah, Jikesh,Zgombick, John M.,Herr, R. Jason,Melekhov, Alex,Sampson, Peter B.,King, Chi-Hsin R.
, p. 744 - 755 (2007/10/03)
The melanocortin receptors have been implicated as potential targets for a number of important therapeutic indications, including inflammation, sexual dysfunction, and obesity. We identified compound 1, an arylpiperazine attached to the dipeptide H-D-Tic-D-p-Cl-Phe-OH, as a novel melanocortin subtype-4 receptor (MC4R) agonist through iterative directed screening of nonpeptidyl G-protein-coupled receptor biased libraries. Structure-activity relationship (SAR) studies demonstrated that substitutions at the ortho position of the aryl ring improved binding and functional potency. For example, the o-isopropyl-substituted compound 29 (Ki = 720 nM) possessed 9-fold better binding affinity compared to the unsubstituted aryl ring (Ki = 6600 nM). Sulfonamide 39 (Ki = 220 nM) fills this space with a polar substituent, resulting in a further 2-fold improvement in binding affinity. The most potent compounds such as the diethylamine 44 (Ki = 60 nM) contain a basic group at this position. Basic heterocycles such as the imidazole 50 (Ki = 110 nM) were similarly effective. We also demonstrated good oral bioavailability for sulfonamide 39.
