It has been reported that 6,7-dimethoxyquinazoline derivatives have cytotoxic potential independent of their 1- adrenoceptor blocking potential. Bioisosteres of 2-arylquinazolines are considered to have anti-tumor properties. In the present study, we have synthesized the 2-aryl and 2-arylmethyl derivatives of quinazolin-4(3H)-one while retaining the 6,7-dimethoxy substituents. Derivatives with n-butyl group attached to position-3 of quinazolinone nucleus were synthesized with the aim of increasing their lipophilicity. The potential of these synthesized compounds was evaluated against NCI (National Cancer Institute) 60 cell panel using the NCI disease oriented antitumor screen protocol. Based on the results of this screening we generalized that compounds having aryl groups directly attached to the quinazoline ring are less active than those which have one atom linker in between the two ring systems. Substitution of a lipophilic group like nbutyl decreases cytotoxic activity among the compounds and 4-aminoquinazolines showed better activity than 4- quinazolinones. Lipophilic groups in the aromatic ring yielded more active compounds as cytotoxic agents. Among the selected compounds, 4h and 13b were found to be potential lead compounds which could be further optimized as potential anti-neoplastic agents.

据报道，6，7-二甲氧基喹唑啉衍生物具有独立于其β1-肾上腺素受体阻断潜能的细胞毒性潜能。2-芳基喹唑啉的生物甾醇被认为具有抗肿瘤特性。在本研究中，我们合成了喹唑啉-4（3H）-one的2-芳基和2-芳基甲基衍生物，同时保留了6,7-二甲氧基取代基。为了增加亲脂性，合成了在喹唑啉酮核的3位上连接有正丁基的衍生物。使用面向NCI疾病的抗肿瘤筛选方案，针对NCI（美国国家癌症研究所）60细胞小组评估了这些合成化合物的潜力。基于该筛选的结果，我们得出的结论是，与直接在喹唑啉环上连接的具有芳基的化合物相比，在两个环系统之间具有一个原子接头的化合物，其活性较低。亲油性基团（如正丁基）的取代降低了化合物之间的细胞毒性活性，而4-氨基喹唑啉的活性优于4-喹唑啉酮。芳环中的亲脂基团产生更多的活性化合物作为细胞毒剂。在选定的化合物中，发现4h和13b是潜在的先导化合物，可以进一步优化为潜在的抗肿瘤药物。芳环中的亲脂基团产生更多的活性化合物作为细胞毒剂。在选定的化合物中，发现4h和13b是潜在的先导化合物，可以进一步优化为潜在的抗肿瘤药物。芳环中的亲脂基团产生更多的活性化合物作为细胞毒剂。在选定的化合物中，发现4h和13b是潜在的先导化合物，可以进一步优化为潜在的抗肿瘤药物。