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

作者：Lauria Antonino^*; Patella Chiara; Abbate Ilenia; Martorana Annamaria; Almerico Anna Maria

来源：European Journal of Medicinal Chemistry, 2013, 65: 381-388.

DOI：10.1016/j.ejmech.2013.05.012

• Annelated thienotriazolopyrimidines
• Domino reactions
• Dimroth rearrangement
• Developmental Therapeutics Program (DTP)
• Anticancer agents

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.

• 出版日期2013-7