Rafat M Mohareb 1 , Amr S Abouzied 2,3 , Nermeen S Abbas 4,5 . Show Affiliations »
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. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
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. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
Entities: Chemical
Disease
Gene
Keywords:
1; 2-aminoprop-1-ene-1; 3-tricarbonitrile; antiproliferative activity.; kinase inhibitors; pyran; pyridine
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Substances: See more »
Year: 2018
PMID: 28745236 DOI: 10.2174/1871520617666170725153523
Source DB: PubMed Journal: Anticancer Agents Med Chem ISSN: 1871-5206 Impact factor: 2.505