论文部分内容阅读
Hedgehog信号通路是近年来抗肿瘤靶向治疗药物研究的一个新热点.本研究以4-(嘧啶-2-氨基)苯甲酰胺为母核,基于先导化合物1的构效关系,设计并合成了14个未见文献报道的4-(嘧啶-2-氨基)苯甲酰胺类Hedgehog信号通路抑制剂,并进行了初步的抗Hedgehog信号通路活性筛选.结果表明:所合成的化合物均表现出较好的Hedgehog信号通路抑制活性,其中化合物8e的活性最好,IC50为5.0 nmol?L-1,高于阳性药GDC-0449;同时在体内药代性质研究中,8e相比化合物1,药代性质均有所改善.
Hedgehog signaling pathway is a new hotspot in the research of anti-tumor targeted therapies in recent years.In this study, based on the structure-activity relationship of lead 1, 4- (pyrimidin-2-amino) benzamide was designed and synthesized 14 unidentified 4- (pyrimidin-2-amino) benzamide class Hedgehog signaling pathway inhibitors, and preliminary anti-Hedgehog signaling pathway activity screening results show that: the compounds are shown to be better Hoechst and Hedgehog signaling pathways. Among them, compound 8e showed the best activity with an IC50 of 5.0 nmol? L-1, which was higher than that of GDC-0449. In addition, compared with compound 1, pharmacokinetics All improved.