2-(1-取代哌啶-4-氨基) 喹唑啉类化合物的合成及抗肿瘤活性研究

Synthesis and antitumor activity of novel 2-(1-substituted- piperidin-4-ylamino)quinazolines as antitumor agents

摘要:
本文合成了一系列新结构的2-(1-取代哌啶-4-氨基) 喹唑啉衍生物, 采用MTT法评价了化合物对5种肿瘤细胞系的抑制活性。研究结果表明: 在哌啶环上引入小体积的疏水性烷基取代基, 得到的化合物4j～4l、5a、5b和5d具有较强的细胞毒活性, IC₅₀值在微摩尔水平。在小鼠移植瘤模型实验中, 化合物4l表现出了较强的体内抗肿瘤活性, 在200 mg·kg⁻¹的剂量下, 对H22肿瘤生长抑制率为72.9%, 对Lewis肺癌的抑制率达到了80%。

Abstract:
A variety of novel 2-(1-substituted-piperidine-4-ylamino)quinazoline derivatives were prepared and their antiproliferative activities on five cancer cell lines were evaluated by MTT assay. Quinazolines 4j−4l, 5a, 5b and 5d bearing a small hydrophobic alkyl group on piperidine ring exhibited potent antitumor activities with IC₅₀ values at micromolar level. Compound 4l displayed significant in vivo antitumor activity with 72.9% inhibition on H22 tumor growth and 80% inhibition on Lewis lung cancer growth at a dose of 200 mg·kg⁻¹.