Design and biological evaluation of 3-aryl-4-alkylpyrazol-5-amines based on the target fishing.

Abstract

BACKGROUND\nPyrazol-5-amine derivatives are an important class of heterocyclic compounds. However, there are less 4-alkyl substituted pyrazoles reported.\n\n\nOBJECTIVE\nHere reported are the design, synthesis and biological evaluation of 3-aryl-4-alkylpyrazol-5-amines derivatives.\n\n\nMETHOD\nA 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 MTT method using U-2 OS (osteosarcoma) and A549 (lung cancer) tumor cells.\n\n\nRESULTS\nEight 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 1.3 µM., respectively.\n\n\nCONCLUSION\nCompound 5h might represent a promising scaffold for the further development of novel antitumor drugs.