6890-75-1Relevant articles and documents
Design, synthesis, and biological evaluation of amide imidazole derivatives as novel metabolic enzyme CYP26A1 inhibitors
Sun, Bin,Liu, Kai,Han, Jing,Zhao, Li-Yu,Su, Xiao,Lin, Bin,Zhao, Dong-Mei,Cheng, Mao-Sheng
, p. 6763 - 6773 (2015)
All-trans-retinoic acid (ATRA) as a physiological metabolite of vitamin A is widely applied in the treatment of cancer, skin, neurodegenerative and autoimmune diseases. CYP26A1 enzyme, induced by ATRA in liver and target tissues, metabolizes ATRA into 4-hydroxyl-RA. Inhibition of CYP26A1 metabolic enzyme represents a promising strategy for discovery of new specific anticancer agents. Herein, we describe the design, synthesis and biological evaluation of a series of new amide imidazole derivatives as retinoic acid metabolism blocking agents (RAMBAs) toward CYP26A1 enzyme. First, based on the recent theoretical models (Sun et al., J. Mol. Graph. Model., 2015, 56, 10-19) a series of RAMBAs with novel scaffolds were designed using fragment-based drug discovery approach. Subsequently, the new RAMBAs were synthesized and evaluated for their biological activities. All the compounds demonstrated appropriate enzyme activities and cell activities. The promising inhibitors 20 and 23 with IC50 value of 0.22 μM and 0.46 μM toward CYP26A1, respectively, were further evaluated for CYP selectivity and the metabolic profile of ATRA. Both compounds 20 and 23 showed higher selectivity for CYP26A1 over other CYPs (CYP2D6, CYP3A4) when compared to liarozole. They also showed better inhibitory activities for the metabolism of ATRA when also compared to liarozole. These studies further validated the pharmacophore and structure-activity relationship models obtained about CYP26A1 inhibitors and highlighted the promising activities of the new series of CYP26A1 inhibitors designed from such models. They also paved the way for future development of those candidates as potential drugs.
PRODUCTION METHOD OF BENZOTHIAZOLE DERIVATIVE
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Paragraph 0320; 0324, (2020/06/18)
PROBLEM TO BE SOLVED: To provide: a production method of a benzothiazole derivative; as well as a production method of a polymerizable compound produced from the benzothiazole derivative; a polymerizable composition including the polymerizable compound; a polymer obtained by polymerizing the polymerizable composition; and an optical isomer utilizing the polymer. SOLUTION: A production method of a compound represented by the following general formula (III) is provided, and also a production method of a polymerizable compound produced from the compound represented by the general formula (III), a polymerizable composition, a polymer obtained by polymerizing the polymerizable composition, and an optical isomer utilizing the polymer are provided. When the polymerizable composition containing the compound is polymerized and the obtained film-like polymer is irradiated with ultraviolet light, change of color and change of phase difference scarcely take place. SELECTED DRAWING: None COPYRIGHT: (C)2020,JPOandINPIT
Tris(benzotriazol-1-yl)methane: A -CO2H Synthon for the Preparation of Carboxylic Acids
Katritzky, Alan R.,Yang, Zhijun,Lam, Jamshed N.
, p. 666 - 669 (2007/10/02)
Lithiation of tris(benzotriazol-1-yl)methane 16 gives the tris(benzotriazolyl)methyl carbanion 17 which affords substitution products 18 with many electrophiles.Acidic hydrolysis of 18 affords the corresponding carboxylic acids 19 in good yield.The syntheses of several α-functionalized carboxylic acids are described.
