A series of some novel (E)-2-methyl/propyl-4-[(2-(substitutedbenzylidene)hydrazinyl]-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidines was synthesized and characterized by adopting an appropriate synthetic scheme. The effect of electron withdrawing and electron donating groups at the aromatic ring in presence of methyl and propyl substituents at the 2-position of the scaffold was evaluated for anthelmintic activity against adult Indian earthworms (Pheretima posthuma). Among 2-methyl-thieno[2,3-d]pyrimidine analogs, compounds with electron donating methoxy group either at para-position or at meta and para-positions of the aromatic ring showed potent anthelmintic activity at 100 μg/ml (284 and 261.8 μM concentrations) for compounds 5g and 5h with a mean paralytic time of 2.32, 2.22 min, and helminthicidal time of 22.38, 19.43 min, respectively. In contrast, the presence of electron withdrawing chloro group at ortho and para-position of the aromatic ring was found to be favorable for the anthelminthic activity of the compounds 5n and 5o (at concentration of 259.7 μM) with propyl group at the 2-position of the thieno[2,3-d]pyrimidine scaffold, exhibiting mean paralytic time of 2.5 min, 2.81 min and helminthicidal time of 21, 20.03 min, respectively. Anthelmintic activities of these four compounds 5g, 5h, 5n, and 5o (at the concentrations of 284, 261.8, 259.7, and 259.7 μM, respectively) were found to be on par with the standard drug piperazine adipate (time for paralysis and death at 6.25 and 24.5 min, respectively) at concentration of 100 μg/ml (431.03 μM). Overall, the potency of these compounds (5g, 5h, 5n, and 5o) is better than standard drug as they exhibited the same activity at 259.7–284 μM as that of a standard drug (which has shown the same activity at 431.03 μM). Further, the predicted ADME properties of all the synthesized compounds were found to be in the satisfactory ranges as predicted by SwissADME software and found to have drug-like properties. Thus, further modification of these compounds might lead to the discovery of more potent analogs.

中文翻译：

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某些新型（E）-2-甲基/丙基-4-（2-（取代亚苄基）肼基）-5,6,7,8-四氢苯并[4,5]噻吩并[2,3- d]的合成及驱虫活性嘧啶类

一系列新的（E）-2-甲基/丙基-4-[（2-（取代的亚苄基）肼基] -5,6,7,8-四氢苯并[4,5]噻吩并[2,3- d ]嘧啶通过适当的合成方案合成并表征。评估了支架2位上存在甲基和丙基取代基的芳香环上的吸电子和供电子基团对成年印度earth（Pheretima）的驱虫活性posthuma），其中2-甲基-噻吩并[2,3- d ]嘧啶类似物，用电子化合物无论在供甲氧基对-位或在间位和对位化合物5g和5h的芳环的-位置在100μg/ ml（浓度为284和261.8μM）下显示出有效的驱虫活性，其平均麻痹时间分别为2.32、2.22 min和杀虫时间为22.38、19.43 min。相反，发现在芳环的邻位和对位存在吸电子氯基团对化合物5n和5o（浓度为259.7μM）在2-位具有丙基的驱虫活性是有利的thieno [2,3- d嘧啶支架，分别显示平均麻痹时间为2.5分钟，2.81分钟和杀虫剂时间为21、20.03分钟。发现这四种化合物5g，5h，5n和5o的驱虫活性（分别为284、261.8、259.7和259.7μM的浓度）与标准药物哌嗪己二酸酯（在瘫痪和死亡时）相一致。浓度分别为100μg/ ml（431.03μM）和6.25和24.5分钟。总体而言，这些化合物的效力（5g，5h，5n和5o）优于标准药物，因为它们在259.7–284μM处显示出与标准药物（在431.03μM处显示出相同的活性）相同的活性。此外，发现所有合成化合物的预测ADME性质都在SwissADME软件预测的令人满意的范围内，并且具有类药物性质。因此，这些化合物的进一步修饰可能导致发现更有效的类似物。