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Current Computer-Aided Drug Design


ISSN (Print): 1573-4099
ISSN (Online): 1875-6697

Research Article

Design and Biological Evaluation of 3-Aryl-4-alkylpyrazol-5-amines Based on the Target Fishing

Author(s): Shuchao Ma, Ben Ouyang, Linan Wang and Lei Yao*

Volume 16, Issue 5, 2020

Page: [564 - 570] Pages: 7

DOI: 10.2174/1573409915666191003123900

Price: $65


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.

Keywords: Target fishing, 3-aryl-4-alkylpyrazol-5-amines, design, synthesis, antitumor, P53.

Graphical Abstract
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