Application of 844501-71-9In 2011 ,《SAR studies of 4-pyridyl heterocyclic anilines that selectively induce autophagic cell death in von Hippel-Lindau-deficient renal cell carcinoma cells》 appeared in Bioorganic & Medicinal Chemistry. The author of the article were Bonnet, Muriel; Flanagan, Jack U.; Chan, Denise A.; Lai, Edwin W.; Nguyen, Phuong; Giaccia, Amato J.; Hay, Michael P.. The article conveys some information:
We recently identified a class of pyridyl aniline thiazoles (PAT) that displayed selective cytotoxicity for von Hippel-Lindau (VHL) deficient renal cell carcinoma (RCC) cells in vitro and in vivo. Structure-activity relationship (SAR) studies were used to develop a comparative mol. field anal. (CoMFA) model that related VHL-selective potency to the three-dimensional arrangement of chem. features of the chemotype. We now report the further mol. alignment-guided exploration of the chemotype to discover potent and selective PAT analogs. The contribution of the central thiazole ring was explored using a series of five- and six-membered ring heterocyclic replacements to vary the electronic and steric interactions in the central unit. We also explored a pos. steric CoMFA contour adjacent to the pyridyl ring using Pd-catalyzed cross-coupling Suzuki-Miyaura, Sonogashira and nucleophilic displacement reactions to prepare of a series of aryl-, alkynyl-, alkoxy- and alkylamino-substituted pyridines, resp. In vitro potency and selectivity were determined using paired RCC cell lines: the VHL-null cell line RCC4 and the VHL-pos. cell line RCC4-VHL. Active analogs selectively induced autophagy in RCC4 cells. We have used the new SAR data to further develop the CoMFA model, and compared this to a 2D-QSAR method. Our progress towards realizing the therapeutic potential of this chemotype as a targeted cytotoxic therapy for the treatment of RCC by exploiting the absence of the VHL tumor suppressor gene is reported. The experimental part of the paper was very detailed, including the reaction process of 3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole(cas: 844501-71-9Application of 844501-71-9)
3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole(cas: 844501-71-9) belongs to pyrazoles. Pyrazoles are commonly used scaffold molecules in drug discovery projects. The use of pyrazole derivatives is based on their analgesic, neuroleptic, anticonvulsant, monoamine oxidase inhibitory, anti-inflammatory, antipyretic, antiarrhythmic, sedative, muscle relaxant, antidiabetic and antibacterial activities. Application of 844501-71-9
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