174855-53-9Relevant academic research and scientific papers
INHIBITORS OF CYCLIN-DEPENDENT KINASE 7 (CDK7)
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, (2015/12/24)
The present invention provides novel compounds described herein, such as of Formula (I), and pharmaceutically acceptable salts, solvates, hydrates, tautomers, stereoisomers, isotopically labeled derivatives, and compositions thereof. Also provided are methods and kits involving the compounds or compositions for treating or preventing proliferative diseases (e.g., cancers (e.g., leukemia, melanoma, multiple myeloma), benign neoplasms, angiogenesis, inflammatory diseases, autoinflammatory diseases, and autoimmune diseases) in a subject. Treatment of a subject with a proliferative disease using a compound or composition of the invention may inhibit the aberrant activity of cyclin-dependent kinase 7 (CDK7), and therefore, induce cellular apoptosis and/or inhibit transcription in the subject.
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.
Substituted aryl piperazines as neurokinin antagonists
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, (2008/06/13)
Disclosed are substituted aryl piperazines of Formula I STR1 are tachykinin receptor antagonists useful in the treatment of inflammatory diseases, pain or migraine, asthma and emesis. In particular compounds of Formula I are shown to be neurokinin antagonists.
