The 4‐anilinoquinazoline PD 153035 (1) is a potential antitumor agent which acts by inhibiting tyrosine kinase activity of epidermal growth factor receptor (EFGR) via competitive binding at the ATP site of enzyme. A series of cyclic analogues of PD 153035 bearing the 1,4‐dioxane ring was prepared by reaction of 6‐chloro derivative 5 with several aniline nucleophiles. These were evaluated for their ability to inhibit the EGFR kinase and the growth of primary human tumor cell cultures. All of the new 4‐anilinoquinazolines exhibited less potency than PD 153035 against EGFR kinase. However, compounds 2b, 2c, 2e, 2g, and 2h showed higher inhibitory activities than PD 153035 against the growth of A431 tumor cell line. The compound 2b containing 3‐chloroaniline ring was as potent as PD 153035 against EGFR kinase and showed about 5.4‐fold better potency than PD153035 in the inhibition of growth of A431 cell line with good selectivity.

中文翻译：

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1,4-二恶烷融合的 4-苯胺基喹唑啉作为表皮生长因子受体激酶抑制剂

4-苯胺基喹唑啉 PD 153035 (1) 是一种潜在的抗肿瘤剂，通过与酶的 ATP 位点的竞争性结合来抑制表皮生长因子受体 (EFGR) 的酪氨酸激酶活性。通过 6-氯衍生物 5 与几种苯胺亲核试剂的反应，制备了一系列带有 1,4-二恶烷环的 PD 153035 环状类似物。评估了它们抑制 EGFR 激酶和原代人类肿瘤细胞培养物生长的能力。所有新的 4-苯胺基喹唑啉对 EGFR 激酶的效力均低于 PD 153035。然而，化合物 2b、2c、2e、2g 和 2h 对 A431 肿瘤细胞系的生长显示出比 PD 153035 更高的抑制活性。含有 3-氯苯胺环的化合物 2b 与 PD 153035 一样有效对抗 EGFR 激酶，显示约 5。