Title:Synthesis of Pyridine and Spiropyridine Derivatives Derived from 2-aminoprop- 1-ene-1,1,3-tricarbonitrile Together with their c-Met Kinase and Antiproliferative Evaluations
VOLUME: 17 ISSUE: 14
Author(s):Rafat M. Mohareb*, Amr S. Abouzied and Nermeen S. Abbas
Affiliation:Department of Chemistry, Faculty of Science, Cairo University, Giza, Department of Pharmaceutical Chemistry, College of Pharmacy, University of Hail, Hail, Department of Chemistry, Faculty of Science, Taibah University
Keywords:2-aminoprop-1-ene-1, 1, 3-tricarbonitrile, pyran, pyridine, kinase inhibitors, antiproliferative activity.
Abstract:Background: Among a wide range of pyridines, 3-cyanopyridines acquired a special attention due to
their wide range of pharmacological activities especially the therapeutic activities. Many pharmacological drugs
containing the pyridine nucleus were known in the market.
Objective: The aim of this work was to synthesize target molecules not only possess anti-tumor activities but
also kinase inhibitors. To achieve this goal, our strategy was to synthesize a series of 3-cyanopyridine derivatives
using 2-aminoprop-1-ene-1,1,3-tricarbonitrile (1) as the key starting material for many heterocyclization
reactions.
Method: Muticoponent reactions were adopted using compound 1 to get different pyridine derivatives that were
capable for different heterocyclization reactions.
Results: Antiproliferative evaluations and c-Met kinase, Pim-1 kinse inhibitions were perform where some
compounds gave high activities.
Conclusion: Compounds that showed high antiprolifeative activity were tested gor c-Met-independent and the
results showed that compounds 5c, 5e, 5f, 7c, 7f and 16d were more active than foretinib. The Pim-1 kinase
inhibition activity of some selected compounds showed that compounds 5e and 16c were high potent to inhibit
Pim-1 activity.
