Department of Organic Synthesis, University of Chemical Technology and Metallurgy, 8Kliment Ohridski Blvd., 1756 Sofia, Bulgaria.
Eur J Med Chem. 2010 Dec;45(12):5856-61. doi: 10.1016/j.ejmech.2010.09.050. Epub 2010 Sep 25.
Some novel thieno[2,3-d]pyrimidin-4(3H)-ones containing benzimidazol-2-yl-thioethyl- and benzimidazol-2-yl-methanethioethyl moiety in second position of the pyrimidine ring were synthesized in order to determine their antitrichinellosis and antiprotozoal effects. The structures of the compounds were confirmed by IR, (1)H NMR and elemental analysis. The antiparasitic screening showed that the benzimidazole derivatives of thieno[2,3-d]pyrimidin-4(3H)-ones exhibited higher activity against Trichinella spiralis in vitro in comparison albendazole. The most active compound, 2-[2-(5-nitro-1H-benzimidazol-1-yl)ethyl]-5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidin-4(3H)-one 22 revealed 95% activity at a dosage of 5 mg/kg mw after 24 h, while compounds 8 and 10 applied at the same dose showed efficacy of 90% after 48 h. The compound 2-{2-[(5(6)-nitro-1H-benzimidazol-2-yl)thio]ethyl}-5,6,7,8-tetrahydro[1]-benzothieno[2,3-d]pyrimidin-4(3H)-one 11 exhibited 90% efficacy after 24 h. The pharmaco-therapeutic study in vivo on invaded with Lamblia muris white mice showed 100% effectiveness of the compounds 8, 10, 11, 13-15 and 22, 23 after five-days-treatment course.
为了测定它们的抗旋毛虫病和抗原生动物作用,合成了一些新型的噻吩并[2,3-d]嘧啶-4(3H)-酮,其中嘧啶环的第二个位置含有苯并咪唑-2-基-硫乙基-和苯并咪唑-2-基-甲硫基乙基部分。通过红外光谱(IR)、(1)H NMR 和元素分析确认了化合物的结构。寄生虫筛选表明,与阿苯达唑相比,噻吩并[2,3-d]嘧啶-4(3H)-酮的苯并咪唑衍生物对旋毛虫具有更高的体外活性。最活跃的化合物 2-[2-(5-硝基-1H-苯并咪唑-1-基)乙基]-5,6,7,8-四氢[1]苯并噻吩并[2,3-d]嘧啶-4(3H)-酮 22 在 5mg/kg 剂量下 24 小时后显示出 95%的活性,而在相同剂量下应用的化合物 8 和 10 在 48 小时后显示出 90%的疗效。化合物 2-{2-[(5(6)-硝基-1H-苯并咪唑-2-基)硫]乙基}-5,6,7,8-四氢[1]-苯并噻吩并[2,3-d]嘧啶-4(3H)-酮 11 在 24 小时后表现出 90%的疗效。体内对感染有兰氏贾第鞭毛虫的小白鼠进行的药物治疗研究表明,化合物 8、10、11、13-15 和 22、23 在五天的疗程后具有 100%的疗效。