细胞周期蛋白依赖激酶
配体效率
化学
IC50型
立体化学
氢键
激酶
组合化学
铅化合物
李宾斯基五定律
CDK抑制剂
配体(生物化学)
生物信息学
生物化学
有机化学
细胞周期
体外
受体
细胞
分子
基因
作者
Razan Eskandrani,Lamees S. Al-Rasheed,Siddique Akber Ansari,Ahmed H. Bakheit,Abdulrahman A. Almehizia,Maha S. Almutairi,Hamad M. Alkahtani
出处
期刊:Molecules
[MDPI AG]
日期:2023-05-23
卷期号:28 (11): 4271-4271
被引量:4
标识
DOI:10.3390/molecules28114271
摘要
Cyclin-dependent kinases (CDKs) are promising targets in chemotherapy. In this study, we report a series of 2-anilinopyrimidine derivatives with CDK inhibitory activity. Twenty-one compounds were synthesized and their CDK inhibitory and cytotoxic activities were evaluated. The representative compounds demonstrate potent antiproliferative activities toward different solid cancer cell lines and provide a promising strategy for the treatment of malignant tumors. Compound 5f was the most potent CDK7 inhibitor (IC50 = 0.479 µM), compound 5d was the most potent CDK8 inhibitor (IC50 = 0.716 µM), and compound 5b was the most potent CDK9 inhibitor (IC50 = 0.059 µM). All the compounds satisfied the Lipinski's rule of five (molecular weight < 500 Da, number of hydrogen bond acceptors <10, and octanol-water partition coefficient and hydrogen bond donor values below 5). Compound 5j is a good candidate for lead optimization because it has a non-hydrogen atom (N) of 23, an acceptable ligand efficiency value of 0.38673, and an acceptable ligand lipophilic efficiency value of 5.5526. The synthesized anilinopyrimidine derivatives have potential as anticancer agents.
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