165283-98-7Relevant academic research and scientific papers
The effect of a thieno[2,3-b]pyridine PLC-γ inhibitor on the proliferation, morphology, migration and cell cycle of breast cancer cells
Leung, Euphemia,Hung, Joy M.,Barker, David,Reynisson, Johannes
, p. 99 - 106 (2014)
3-Amino-N-(3-chlorophenyl)-5-oxo-5,6,7,8-tetrahydrothieno[2,3-b] quinoline-2-carboxamide (compound 1) is a putative phosphoinositide specific-phospholipase C-γ (PLC-γ) enzyme inhibitor. This enzyme is a plausible anticancer target linked to cell motility, important for the invasion and dissemination of tumour cells. In this work it is shown that IC50 values of compound 1 are in the low nanomolar range against a host of breast cancer cell lines as a consequence of anti-proliferative activity. These results correlate well with previously published results (Feng et al., Eur. Med. Chem., 54, 2012, 463-469) on tumour cell viability confirming the efficacy of compound 1. Flow cytometry experiments revealed that compound 1 arrests the cell cycle in the G2/M phases. Furthermore, the morphology and cell migration for the MDA-MB-231 breast cancer cell line are severely affected by administration of compound 1, which fits the hypothesis of PLC-γ inhibition. Finally, a detailed docking study against PLC reveals that the side chains of the amino acids His356, Glu341, Arg549 and Lys438 are involved in hydrogen bonding with ligand 1 as well as a lipophilic pocket is occupied by the phenyl moiety. The results presented in this study are particularly interesting because compound 1 affects triple-negative breast cancer cells, which are difficult to treat in the clinic and are in a dire need for an effective targeted therapy. We believe that compound 1 and its thieno[2,3-b]pyridine derivatives demonstrate that such a therapy can be developed.
Enaminones as building blocks in heterocyclic syntheses: A new approach to polyfunctionally substituted cyclohexenoazines
Al-Mousawi, Saleh,Abdelkhalik, Mervat Mohammed,John, Elizabeth,Elnagdi, Mohammed Hilmy
, p. 689 - 695 (2003)
A variety of polyfunctionally substituted condensed pyridines and pyrazolotetrahydroquinazolines have been synthesized utilizing cyclic enaminones as starting materials.
Synthesis and antiproliferative activity of 2-chlorophenyl carboxamide thienopyridines
van Rensburg, Michelle,Leung, Euphemia,Haverkate, Natalie A.,Eurtivong, Chatchakorn,Pilkington, Lisa I.,Reynisson, Jóhannes,Barker, David
supporting information, p. 135 - 138 (2016/12/27)
3-Amino-2-arylcarboxamide-thieno[2,3-b]pyridines are a known class of antiproliferative compounds with activity against the phospholipase C enzyme. To further investigate the structure activity relationships of these derivatives a series of analogues were prepared modifying key functional groups. It was determined that modification of the 3-amino and 2-aryl carboxamide functionalities resulted in complete elimination of activity, whilst modification at C-5 allowed compounds of greater activity to be prepared.
Synthesis and cytotoxicity of thieno[2,3-b]pyridine and furo[2,3-b]pyridine derivatives
Hung, Joy M.,Arabshahi, Homayon J.,Leung, Euphemia,Reynisson, Jóhannes,Barker, David
, p. 420 - 437 (2015/02/19)
Forty seven thieno[2,3-b]pyridines-2-carboxamides, furo[2,3-b]pyridines-2-carboxamides and tetrahydrothieno[2,3-b]quinolones-2-carboxamides derivatives were synthesized and tested for their antiproliferative activity against the NCI-60 cell lines. The 5-keto-tetrahydrothieno[2,3-b]quinolones-2-carboxamides (series 17) were found to have the greatest activity, with the compound containing a 3-methoxyphenylcarboxamide (compound 17d) being the most active, with GI50values in the low nanomolar range against a range of cell lines, in particular the melanoma cell line MDA-MD-435 (GI50- 23 nM) and the breast cancer cell line MDA-MB-468 (GI50- 46 nM). Molecular modelling of series 17 against phosphoinositide specific-phospholipase C reveals that the side chains of the amino acids His356, Glu341, Arg549 and Lys438 are involved in hydrogen bonding with the ligands as well as a lipophilic pocket is occupied by the phenyl carboxamide moiety.
Anilinomethylidene derivatives of cyclic 1,3-dicarbonyl compounds in the synthesis of new sulfur-containing pyridines and quinolines
Dotsenko,Krivokolysko,Chernega,Litvinov
, p. 1556 - 1561 (2007/10/03)
Simple methods for the synthesis of previously unknown sulfur-containing pyridin-2-ones and 5,6,7,8-tetrahydroquinolines from cyanothioacetamide and anilinomethylidene derivatives of cyclic 1,3-dicarbonyl compounds were developed. Structures and chemical transformations of compounds obtained were studied.
Synthesis of 2,3,5,6-tetrasubstituted pyridines from enamines derived from N,N-dimethylformamide dimethyl acetal
Abu-Shanab,Redhouse,Thompson,Wakefield
, p. 557 - 560 (2007/10/02)
Reactions of 1,3-dicarbonyl compounds with N,N-dimethylformamide dimethyl acetal, followed by cyanothioacetamide or cyanoacetamide and sodium hydride, then acidification, give 5,6-disubstituted 3-cyanopyridine-2(1H)-thiones or 5,6-disubstituted 3-cyanopyridin-2(1H)-ones 4. Analogous reactions with the malononitrile dimer give 5,6-disubstituted 3-cyano-2-(dicyanomethylene)-1,2-dihydropyridines 9.
