SYNTHESIS AND ANTITUMOR ACTIVITY OF 6-(H/Me)-N-(5-R-BENZYL-1,3-THIAZOL-2-YL)-4,5,6,7-TETRAHYDRO-1-BENZOTHIOPHENE-3-CARBOXAMIDES
DOI:
https://doi.org/10.11603/2312-0967.2017.2.7912Keywords:
thiazole, chloroarylation, antitumor activity.Abstract
The aim of the work. Synthesis of new 6-(N/Me)-N-(5-R-benzyl-1,3-thiazol-2-yl)-4,5,6,7-tetrahydro-1-benzothiophen-3-carboxamides and investigation of their antitumor activity.
Materials and Methods. It was used traditional methods of organic synthesis during performing of experimental part. The key starting reagents synthesized by known methods from commercially available reagents. The 1H and 13C NMR spectra of the synthesized compounds were recorded on a Varian VXR-400 instrument, DMSO-d6 solvent, tetramethylsilane standard. Study of the antitumor activity of synthesized compounds was carried out within the framework of the international scientific program DTP (Developmental Therapeutic Program) of the National Cancer Institute (NCI, Bethesda, Maryland, USA).
Results and Discussion. The new series of 6-(H/Me)-N-(5-R-benzyl-1,3-thiazol-2-yl)-4,5,6,7-tetrahydro-1-benzothiophen-3-carboxamides (5a-h) were synthesized. The antitumor activity of N-[5-(3-hlorobenzyl)-1,3-thiazol-2- yl]-4,5,6,7-tetrahydro-1-benzothiophen-3-carboxamide (5b), N-(5-benzyl-1,3-thiazol-2-yl-6-methyl-4,5,6,7-tetrahydro-benzothiophen-3-carboxamide (5d) and 6-metyl-N-{5-[2-chloro-5-(trifluoromethyl)benzyl]-1,3-thiazol-2-yl}-4,5,6,7-tetrahydro-1-benzothiophen-3-carboxamide (5h) were studied. It was established that the compounds 5b and 5d have significant antitumor effect.
Conclusions. A series of new thiazole derivatives were synthesized, two of which showed a high ability to inhibit the in vitro growth of human tumor cells. It is shown that 5-arylmetylthiazole derivatives are promising to search for innovative anti-cancer agents.
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