An unexpected Dimroth rearrangement leading to annelated thieno[3,2-d][1,2,3]triazolo[1,5-a]pyrimidines with potent antitumor activity

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• 作者：Antonino Lauria ; Chiara Patella ; Ilenia Abbate ; Annamaria Martorana ; Anna Maria Almerico
• 关键词：Annelated thienotriazolopyrimidines ; Domino reactions ; Dimroth rearrangement ; Developmental Therapeutics Program (DTP) ; Anticancer agents
• 刊名：European Journal of Medicinal Chemistry
• 出版年：2013
• 出版时间：July, 2013
• 年：2013
• 卷：65
• 期：Complete
• 页码：381-388
• 全文大小：735 K

文摘

An unusual Dimroth rearrangement occurring in the reaction leading to annelated thieno[2,3-e][1,2,3]triazolo[1,5-a]pyrimidine core allowed the isolation of the linear isomer thieno[3,2-d][1,2,3]triazolo[1,5-a]pyrimidine. By decorating the linear isomer with the same chains that improved the biological activity of the angular isomers, new annelated thieno[3,2-d][1,2,3]triazolo[1,5-a]pyrimidines were designed and synthesized. They were selected by the Developmental Therapeutics Program (DTP) of the National Cancer Institute (NCI) for the anticancer screening against a panel of 60 human tumor cell lines. The biological results showed that the new derivatives exhibited strong antiproliferative activity up to nanomolar concentration. In?vivo screenings of the most active compound, the N-[2-(1H-imidazol-4-yl)ethyl]-4-(3-phenyl-10-oxo-4,10-dihydrobenzothieno[3,2-d][1,2,3]triazolo[1,5-a]pyrimidin-4-yl)butanamide, showed its low toxicity and high potency.