120239-01-2Relevant academic research and scientific papers
Apoptosis: A target for anticancer therapy with novel cyanopyridines
Ismail, Magda M.F.,Farrag, Amel M.,Harras, Marwa F.,Ibrahim, Mona H.,Mehany, Ahmed B.M.
, (2020)
One of the many methods of treating cancer is to terminate the uncontrolled growth of cancer cells. So, aiming the apoptotic pathway is an exciting approach to finding new anticancer agents. A novel series of cyanopyridines was designed and synthesized for antiproliferative evaluation. 2-Amino-6-(4-(benzyloxy)phenyl)-4-(4-(dimethylamino)phenyl) nicotinonitrile 10f was the most potent inhibitor against the growth of PC-3, and HepG-2 cancer cell lines with IC50 values of 2.04 uM (selectivity index, SI = 78.63, 43, respectively). Also, 10f was safe against the growth of normal human diploid lung fibroblasts cell line (WI-38) with an IC50 value of 160.04 uM. Its analogs, 10b, 10d, 10g, and 11b, were also active against the growth of PC-3, and HepG-2 while against MCF-7 cell line, they displayed good cytotoxic activity compared to the reference standard 5-FU. Remarkably, mechanistic studies indicated that compounds 10b, 10d, 10f, 10g, and 11b stimulated the level of active caspase 3 and boosted the BAX/BCL2 ratio 20–95 folds in comparison to the control. Our results have also indicated that 10b, 10d, 10f, 10g, and 11b exhibited a very potent inhibitory activity against PIM-1 kinase enzyme, where the IC50 values unraveled very potent molecules in the micromolar range (0.47–1.27 μM). Further investigations have shown that 10f, the most potent PIM-1 kinase inhibitor, induced a cell cycle arrest at the G2/M phase. Moreover, in silico evaluation of ADME properties indicated that all the cyanopyridine compounds are orally bioavailable with no permeation to the blood brain barrier.
Divergent syntheses of 2-aminonicotinonitriles and pyrazolines by copper-catalyzed cyclization of oxime ester
Wu, Qifan,Zhang, Yan,Cui, Sunliang
supporting information, p. 1350 - 1353 (2014/04/03)
Copper-catalyzed cyclization of an oxime ester toward divergent heterocycle synthesis is reported. Oxime ester serves as an enamine precursor to cyclize with malononitrile and aldehydes for access to 2-aminonicotinonitriles in a one-pot reaction, while cyclizing with N-sulfonylimines leads to synthesis of pyrazolines.
[5C + 1N] Annulation of 2,4-pentadienenitriles with hydroxylamine: A synthetic route to multi-substituted 2-aminopyridines
Xin, Xiaoqing,Huang, Peng,Xiang, Dexuan,Zhang, Rui,Zhao, Fengyu,Zhang, Ning,Dong, Dewen
, p. 1001 - 1006 (2013/02/26)
A facile and efficient synthetic route to multi-substituted 2-aminopyridines has been developed via a formal [5C + 1N] annulation of readily available 2,4-pentadienenitriles with hydroxylamine (NH2OH) under very mild conditions, which involves
2-Amino-6-furan-2-yl-4-substituted nicotinonitriles as A2a adenosine receptor antagonists
Mantri, Monica,De Graaf, Olivier,Van Veldhoven, Jacobus,G?bly?s, Aniko,Von Frijtag Drabbe Künzel, Jacobien K.,Mulder-Krieger, Thea,Link, Regina,De Vries, Henk,Beukers, Margot W.,Brussee, Johannes,Ijzerman, Adriaan P.
experimental part, p. 4449 - 4455 (2009/06/06)
A2A adenosine receptor antagonists usually have bi- or tricyclic N aromatic systems with varying substitution patterns to achieve desired receptor affinity and selectivity. Using a pharmacophore model designed by overlap of nonxanthine type of previously known A2A antagonists, we synthesized a new class of compounds having a 2-amino nicotinonitrile core moiety. From our data, we conclude that the presence of at least one furan group rather than phenyl is beneficial for high affinity on the A2A adenosine receptor. Compounds 39 (LUF6050) and 44 (LUF6080) of the series had Ki values of 1.4 and 1.0 nM, respectively, with reasonable selectivity toward the other adenosine receptor subtypes, A1, A 2B, and A3. The high affinity of 44 was corroborated in a cAMP second messenger assay, yielding subnanomolar potency for this compound.
