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

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,Egypt

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.

Cite this article as:

Mohareb M. Rafat *, Abouzied S. Amr and Abbas S. Nermeen, 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, Anti-Cancer Agents in Medicinal Chemistry 2017; 17 (14) . https://dx.doi.org/10.2174/1871520617666170725153523