Cage-like amines with norbornane and adamantane frameworks were studied in a versatile, convenient one-pot green synthetic experiment for pyrimidine core annulation via cleavage of a 1H-tetrazole ring. The transannulation was performed without an excess of the reagents and solvent under optimized conditions. As a result, 11 new thieno[2,3-d]pyrimidinones with bulky substituents were obtained in high yields without the need of further purification and with excellent selectivity of the process. The introduced сage-like framework is regarded as a bioisostere of the 2-arylamino moiety. Preliminary screening of the biological activity was performed and 2-{[1-(bicyclo[2.2.1]heptan-2-yl)ethyl]amino}-5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidin-4(3H)-one demonstrated high toxicity toward human leukemia HL-60, cervix carcinoma KB3-1, and colon carcinoma HCT116 cells that correlates well with the results obtained previously for the activity of the compounds with benzylamino substituents.

中文翻译：

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环式噻吩并[2,3-d]嘧啶酮形成的绿色方案中的笼状胺作为有希望的抗癌药

在一个通用的，方便的一锅绿色合成实验中研究了具有降冰片烷和金刚烷骨架的笼状胺，用于通过1 H-四唑环的裂解来嘧啶核的环化。在优化条件下进行转环反应时，无需过量的试剂和溶剂。结果，以高收率获得了11个具有大取代基的新的噻吩并[2,3- d ]嘧啶酮，而无需进一步纯化，并且该方法具有优异的选择性。引入的类似age的框架被认为是2-芳基氨基部分的生物等排体。进行生物活性的初步筛选和2 - {[1-（二环[2.2.1]庚-2-基）乙基]氨基} -5,6,7,8-四氢[1]苯并噻吩并[2,3 --d ]嘧啶-4（3 H）-1对人白血病HL-60，子宫颈癌KB3-1和结肠癌HCT116细胞显示出高毒性，这与先前获得的具有苄基氨基取代基的化合物的活性相关。