260558-83-6Relevant academic research and scientific papers
Synthesis of novel hybrids of pyrazole and coumarin as dual inhibitors of COX-2 and 5-LOX
Shen, Fa-Qian,Wang, Zhong-Chang,Wu, Song-Yu,Ren, Shen-Zhen,Man, Ruo-Jun,Wang, Bao-Zhong,Zhu, Hai-Liang
, p. 3653 - 3660 (2017)
In our previous study, we designed a series of pyrazole derivatives as novel COX-2 inhibitors. In order to obtain novel dual inhibitors of COX-2 and 5-LOX, herein we designed and synthesized 20 compounds by hybridizing pyrazole with substituted coumarin w
Coumarin sulfonamides derivatives as potent and selective COX-2 inhibitors with efficacy in suppressing cancer proliferation and metastasis
Lu, Xiao-Yuan,Wang, Zhong-Chang,Ren, Shen-Zhen,Shen, Fa-Qian,Man, Ruo-Jun,Zhu, Hai-Liang
supporting information, p. 3491 - 3498 (2016/07/21)
Cyclooxygenase-2 is frequently overexpression in malignant tumors and the product PGE2promotes cancer cell progression and metastasis. We designed novel series of coumarin sulfonamides derivatives to improve biological activities of COX-2 inhib
Discovery, synthesis, and biological evaluation of orally active pyrrolidone derivatives as novel inhibitors of p53-MDM2 protein-protein interaction
Zhuang, Chunlin,Miao, Zhenyuan,Zhu, Lingjian,Dong, Guoqiang,Guo, Zizhao,Wang, Shengzheng,Zhang, Yongqiang,Wu, Yuelin,Yao, Jianzhong,Sheng, Chunquan,Zhang, Wannian
, p. 9630 - 9642 (2013/01/16)
The p53-MDM2 interaction has been proved to be a valuable target to develop effective antitumor agents. Novel p53-MDM2 inhibitors bearing pyrrolidone scaffolds were successfully identified by structure-based design. The nanomolar inhibitor 5 possessed good p53-MDM2 inhibitory activity (Ki = 780 nM) due to its hydrophobic and hydrogen bonding interactions with MDM2. Further hit optimization led to the discovery of a number of highly potent pyrrolidone derivatives with improved p53-MDM2 inhibitory activity and in vitro antiproliferative potency. Compounds 41 (Ki = 260.0 nM) and 60a (Ki = 150.0 nM) showed good and selective activity against tumor cells with deleted p53. In addition, these two compounds also effectively inhibited the tumor growth in the A549 xenograft model. Interestingly, compound 41 was proved to be a potent MDM2/MDMX dual inhibitor. The novel pyrrolidone p53-MDM2 inhibitors represent promising lead structures for the development of novel antitumor agents.
