p-Toluenesulfonic acid-catalyzed solvent-free synthesis and biological evaluation of new 1-(4′,6′-dimethylpyrimidin-2′-yl)-5-amino-4H-3-arylpyrazole derivatives

• Published in: Medicinal chemistry research 2014-03, Vol.23 (3), p.1454-1464
• Main Authors: Aggarwal, Ranjana, Bansal, Anshul, Rozas, Isabel, Diez-Cecilia, Elena, Kaur, Amanjot, Mahajan, Ritu, Sharma, Jitender
• Format: Article
• Language: English
• Subjects: Biochemistry; Biomedical and Life Sciences; Biomedicine; Cell Biology; Original Research; Pharmacology/Toxicology
• ISSN: 1054-2523; 1554-8120
• DOI: 10.1007/s00044-013-0751-9

A solvent-free quick synthesis of 1-(4′,6′-dimethylpyrimidin-2′-yl)-5-amino-4 H -3-arylpyrazoles ( 3 ) was accomplished by grinding 2-hydrazino-4,6-dimethylpyrimidine ( 1 ) and β-ketonitriles ( 2 ) in the presence of p -Toluenesulfonic acid as a catalyst. Subsequently, 5-aminopyrazoles ( 3 ) were converted to their corresponding N -acetamide ( 4 ) and N -trifluoroacetamide ( 5 ) derivatives by treating ( 3) with acetic anhydride/acetic acid and trifluoroacetic anhydride/trifluoroacetic acid, respectively. The newly synthesized compounds were fully characterized using IR, NMR ( 1 H, 13 C, and 19 F), mass spectral studies, and elemental analyses. All of the fifteen compounds were screened for their in vitro antibacterial activity against two Gram-positive and two Gram-negative pathogenic bacteria such as Bacillus pumilus , Staphylococcus aureus , Pseudomonas aeruginosa , and Escherichia coli , respectively. Additionally, nine of these compounds were screened for their cytotoxicity against the human Caucasian promyelocytic leukemia (HL-60) cell line using the alamarBlue ® assay. Preliminary results reveal that compounds 3a , 3b , 3d , 5a , and 5d are showing moderate-to-significant cytotoxic and antibacterial activity.