Design, Synthesis, and Biological Evaluation of Potent and Selective Class IIa Histone Deacetylase (HDAC) Inhibitors as a Potential Therapy for Huntington’s Disease was written by Burli, Roland W.;Luckhurst, Christopher A.;Aziz, Omar;Matthews, Kim L.;Yates, Dawn;Lyons, Kathy. A.;Beconi, Maria;McAllister, George;Breccia, Perla;Stott, Andrew J.;Penrose, Stephen D.;Wall, Michael;Lamers, Marieke;Leonard, Philip;Muller, Ilka;Richardson, Christine M.;Jarvis, Rebecca;Stones, Liz;Hughes, Samantha;Wishart, Grant;Haughan, Alan F.;O’Connell, Catherine;Mead, Tania;McNeil, Hannah;Vann, Julie;Mangette, John;Maillard, Michel;Beaumont, Vahri;Munoz-Sanjuan, Ignacio;Dominguez, Celia. And the article was included in Journal of Medicinal Chemistry in 2013.COA of Formula: C8H8BrN This article mentions the following:
Inhibition of class IIa histone deacetylase (HDAC) enzymes have been suggested as a therapeutic strategy for a number of diseases, including Huntington’s disease. Catalytic-site small mol. inhibitors of the class IIa HDAC4, -5, -7, and -9 were developed (e.g., I). These trisubstituted diarylcyclopropanehydroxamic acids were designed to exploit a lower pocket that is characteristic for the class IIa HDACs, not present in other HDAC classes. Selected inhibitors were cocrystd. with the catalytic domain of human HDAC4. We describe the first HDAC4 catalytic domain crystal structure in a “closed-loop” form, which in our view represents the biol. relevant conformation. We have demonstrated that these mols. can differentiate class IIa HDACs from class I and class IIb subtypes. They exhibited pharmacokinetic properties that should enable the assessment of their therapeutic benefit in both peripheral and CNS disorders. These selective inhibitors provide a means for evaluating potential efficacy in preclin. models in vivo. In the experiment, the researchers used many compounds, for example, 4-Bromo-2-cyclopropylpyridine (cas: 1086381-28-3COA of Formula: C8H8BrN).
4-Bromo-2-cyclopropylpyridine (cas: 1086381-28-3) belongs to pyridine derivatives. Pyridines are an important class of heterocycles and occur in polysubstituted forms in many naturally occurring biologically active compounds, drug molecules and chiral ligands. Reduced pyridines, namely tetrahydropyridines, dihydropyridines and piperidines, are found in numerous natural and synthetic compounds. The synthesis and reactivity of these compounds have often been driven by the fact many of these compounds have interesting and unique pharmacological properties. COA of Formula: C8H8BrN