5600-21-5Relevant articles and documents
2-(2-Amino-6-methylpyrimidin-4-yl)-4-arylmethylidene- 5-methyl-2,4-dihydro-3H-pyrazol-3-ones: Design, synthesis, structure, in vitro anti-tubercular activity, and molecular docking study
Erkin, Andrei V.,Gurzhiy, Vladislav V.,Krutikov, Viktor I.,Yurieva, Aleksandra V.,Yuzikhin, Oleg S.
, (2021/07/13)
A series of 2-(2-amino-6-methylpyrimidin-4-yl)-4-arylmethylidene-2,4-dihydro-3H-pyrazol-3-ones 6a-f was in silico predicted to display moderate anti-tubercular activity. To obtain these compounds, the Knoevenagel condensation of the corresponding pyrazol-3-ol 10 with aromatic aldehydes was performed. It was found that arylidenepyrazolones 6b, 6d and 6e bearing 4-diethylamino (6b), 3,4-dimethoxy (6d) and 4-hydroxy-3-methoxy (6e) substituents on the arylidene pendant did possess activity against Mycobacterium tuberculosis H37Rv. Their minimal inhibitory concentrations (MICs = 0.07-0.14 mmol/L) were comparable with MIC value for isoniazid (0.01 mmol/L) used as the reference drug. In accordance with a molecular docking study, a plausible mode of action of arylidenepyrazolones 6b, 6d and 6e was the inhibition of UDP-galactopyranose mutase responsible for the biosynthesis of arabinogalactan, one of the important components of the mycobacterial cell wall. The above results indicated that compounds 6b, 6d and 6e might serve as promising hits in further search for anti-tubercular agents based thereon.
Preparation method of 2-chloro-4-amino-6-methylpyrimidine compound
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Paragraph 0012; 0013, (2020/03/06)
The invention discloses a preparation method of a 2-chloro-4-amino-6-methylpyrimidine compound. The preparation method comprises the steps that 2,4-dichloro-6-methylpyrimidine is used as a raw material, dimethylsulfoxide is used as a solvent, under the temperature of 40 DEG C to 45 DEG C, ammonia gas is introduced for substitution reaction, a required isomer product 2-chloro-4-amino-6-methylpyrimidine with high conversion is obtained, and then is treated into salt after acidification, and the pure final product 2-chloro-4-amino-6-methylpyrimidine compound is obtained by dissociating. Accordingto the preparation method, a purification and separation process which is more conductive to factory scale-up production is provided, the method is easy to operate, the post-treatment operation is simple, column chromatography is not required, salifying and dissociating are only required to purify the product, thus the part-level scale-up production of the product can be effectively achieved, theshortcomings of two routes in an existing technical literature are effectively overcome, and thus the disclosed preparation method has great economic value for lowering the cost.
Synthesis and Investigation of Phthalazinones as Antitubercular Agents
Santoso, Kristiana T.,Cheung, Chen-Yi,Hards, Kiel,Cook, Gregory M.,Stocker, Bridget L.,Timmer, Mattie S. M.
supporting information, p. 1278 - 1285 (2019/02/24)
A series of 2- and 7-substituted phthalazinones was synthesised and their potential as anti-tubercular drugs assessed via Mycobacterium tuberculosis (mc26230) growth inhibition assays. All phthalazinones tested showed growth inhibitory activity (MIC 100 μm), and those compounds containing lipophilic and electron-withdrawing groups generally exhibited better anti-tubercular activity. Several lead compounds were identified, including 7-((2-amino-6-(4-fluorophenyl)pyrimidin-4-yl)amino)-2-heptylphthalazin-1(2H)-one (MIC=1.6 μm), 4-tertbutylphthalazin-2(1H)-one (MIC=3 μm), and 7-nitro-phthalazin-1(2H)-one (MIC=3 μm). Mode of action studies indicated that selected pyrimidinyl-phthalazinones may interfere with NADH oxidation, however, the mode of action of the lead compound is independent of this enzyme. MIC=minimum inhibitory concentration.