Title:Design and Biological Evaluation of 3-Aryl-4-alkylpyrazol-5-amines Based on the Target Fishing
VOLUME: 16 ISSUE: 5
Author(s):Shuchao Ma, Ben Ouyang, Linan Wang and Lei Yao*
Affiliation:School of Pharmacy, Yantai University, Yantai, Shandong, 264005, School of Pharmacy, Yantai University, Yantai, Shandong, 264005, School of Pharmacy, Yantai University, Yantai, Shandong, 264005, School of Pharmacy, Yantai University, Yantai, Shandong, 264005
Keywords:Target fishing, 3-aryl-4-alkylpyrazol-5-amines, design, synthesis, antitumor, P53.
Abstract:
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-
alkylpyrazol-5-amines derivatives.
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.
