Liu, Pingxian published the artcileDesign and synthesis of novel pyrimidine derivatives as potent antitubercular agents, Computed Properties of 1885-29-6, the main research area is ceritinib pyrimidine analog preparation antitubercular mol docking; Antimycobacterial; Ceritinib; Dihydrofolate reductase inhibitors; Pyrimidine derivatives.
The emergence of various drug-resistant Mycobacterium tuberculosis (Mtb) strains has necessitated the exploration of new drugs that lack cross-resistance with existing therapeutics. By screening the MedChemExpress bioactive compound library, ceritinib was identified as a compound with activity against Mtb H37Ra. Ceritinib had a MIC value of 9.0 μM in vitro and demonstrated in vivo efficacy in a BALB/c mouse model infected with autoluminescent H37Ra. Then, 32 novel ceritinib derivatives were synthesized, and their antimycobacterial activities were evaluated in vitro. The antimycobacterial activities of the synthesized compounds were drastically affected by substitutions at position 4 of the pyrimidine nucleus and were enhanced by the presence of 2-isopropoxy-5-methyl-4-(piperidin-4-yl)aniline at position 2 of the pyrimidine nucleus. The in vivo antitubercular activities of the three most potent compounds were evaluated. 5-Chloro-N2-(2-isopropoxy-5-methyl-4-(piperidin-4-yl) phenyl)-N4-(naph thalen-1-yl) pyrimidine-2,4-diamine (I) remarkably reduced the Mtb burden of mice. This result suggested the potential of I as a novel drug with superior antitubercular activities. The results of experiments on the combination of sulfamethoxazole with I and in silico modeling suggest that dihydrofolate reductase is the potential mol. target of I.
European Journal of Medicinal Chemistry published new progress about Antifolates. 1885-29-6 belongs to class nitriles-buliding-blocks, name is 2-Aminobenzonitrile(Flakes or Chunks), and the molecular formula is C7H6N2, Computed Properties of 1885-29-6.
Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts