Roy, Sudeshna; Sileikyte, Justina; Schiavone, Marco; Neuenswander, Benjamin; Argenton, Francesco; Aube, Jeffrey; Hedrick, Michael P.; Chung, Thomas D. Y.; Forte, Michael A.; Bernardi, Paolo; Schoenen, Frank J. published the artcile< Discovery, Synthesis, and Optimization of Diarylisoxazole-3-carboxamides as Potent Inhibitors of the Mitochondrial Permeability Transition Pore>, Application In Synthesis of 29027-20-1, the main research area is diarylisoxazole carboxamide preparation mitochondrial permeability transition pore inhibitor human; structure activity relationship; calcium retention capacity; mitochondria; muscular dystrophy; permeability transition; zebrafish.
The mitochondrial permeability transition pore (mtPTP) is a Ca2+-requiring mega-channel which, under pathol. conditions, leads to the deregulated release of Ca2+ and mitochondrial dysfunction, ultimately resulting in cell death. Although the mtPTP is a potential therapeutic target for many human pathologies, its potential as a drug target is currently unrealized. Herein, an optimization effort initiated around hit, 5-(3-hydroxyphenyl)-N-(3,4,5-trimethoxyphenyl)isoxazole-3-carboxamide, which was found to possess promising inhibitory activity against mitochondrial swelling (EC50<0.39 M) and showed no interference on the inner mitochondrial membrane potential (rhodamine 123 uptake EC50>100 M) is described. This enabled the construction of a series of picomolar mtPTP inhibitors that also potently increase the calcium retention capacity of the mitochondria. Finally, the therapeutic potential and in vivo efficacy of one of the most potent analogs, N-(3-chloro-2-methylphenyl)-5-(4-fluoro-3-hydroxyphenyl)isoxazole-3-carboxamide, was validated in a biol. relevant zebrafish model of collagen VI congenital muscular dystrophies.
ChemMedChem published new progress about Aromatic amines Role: RCT (Reactant), RACT (Reactant or Reagent). 29027-20-1 belongs to class chlorides-buliding-blocks, and the molecular formula is C7H8ClN, Application In Synthesis of 29027-20-1.
Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics