Background: Pyrazol-5-amine derivatives are an important class of heterocyclic compounds.
However, there are less 4-alkyl substituted pyrazoles reported.
Objective: Here reported are the design, synthesis and biological evaluation of 3-aryl-4-
Methods: A serials of 3-aryl-4-alkylpyrazol-5-amines were designed and the biological action targets
were screened by target fishing function of Discovery Studio software. The synthesis route involved
3-oxo-3-arylpropanenitrile formation, alkylation, pyrazole formation, and amides formation.
The antitumor activities of these compounds were carried out by thiazolyl blue tetrazolium bromide
(MTT) method using U-2 OS (osteosarcoma) and A549 (lung cancer) tumor cells.
Results: Eight 3-aryl-4-alkylpyrazol-5-amines were synthesized, and their structures were verified
by 1H NMR, 13C NMR, and HRMS. Thirteen pharmacophores were mapped out by target fishing.
Compound 5h showed anti-proliferation activities against U-2 OS and A549 tumor cell with IC50
value of 0.9 μM and 1.2 μM, respectively.
Conclusion: Compound 5h might represent a promising scaffold for the further development of
novel antitumor drugs.