112722-57-3Relevant academic research and scientific papers
Synthesis and biological evaluation of (3/4-(pyrimidin-2-ylamino)benzoyl)-based hydrazine-1-carboxamide/carbothioamide derivatives as novel RXRα antagonists
Chen, Xiaohui,Fang, Meijuan,Guo, Kaiqiang,Liu, Jie,Liu, Weihao,Qin, Jingbo,Tang, Bowen,Wu, Chunxiao,Wu, Tong,Wu, Zhen,Xu, Jianwen,Zhou, Hu
, p. 880 - 896 (2020/04/07)
Abnormal alterations in the expression and biological function of retinoid X receptor alpha (RXRα) have a key role in the development of cancer. Potential modulators of RXRα as anticancer agents are explored in growing numbers of studies. A series of (4/3-(pyrimidin-2-ylamino)benzoyl)hydrazine-1-carboxamide/carbothioamide derivatives are synthesised and evaluated for anticancer activity as RXRα antagonists in this study. Among all synthesised compounds, 6A shows strong antagonist activity (half maximal effective concentration (EC50) = 1.68 ± 0.22 μM), potent anti-proliferative activity against human cancer cell lines HepG2 and A549 cells (50% inhibition of cell viability (IC50) values 50 values > 100 μM). Further bioassays indicate that 6A inhibits 9-cis-RA-induced activity in a dose-dependent manner, and selectively binds to RXRα-=LΒD with submicromolar affinity (Kd = 1.20 × 10?7 M). 6A induces time-and dose-dependent cleavage of poly ADP-ribose polymerase, and significantly stimulates caspase-3 activity, leading to RXRα-dependent apoptosis. Finally, molecular docking studies predict the binding modes for RXRα-LBD and 6A.
N-PHENYL-2-PYRIMIDINE-AMINE DERIVATIVES AND PROCESS FOR THE PREPARATION THEREOF
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Page/Page column 10-11, (2008/06/13)
The present invention relates to a novel N-phenyl-2-pyrimidine-amine derivative represented by the above formula (1) and its salt showing a superior effect on cancer in warm-blooded animals, such as lung cancer, gastric cancer, colon cancer, pancreatic cancer, hepatoma, prostatic cancer, breast cancer, chronic or acute leukemia, hematologic malignancy, encephalophyma, bladder cancer, rectal cancer, cervical cancer, lymphoma, etc. The present invention also relates to a process for preparing the compound, and to a pharmaceutical composition for the treatment of the above various diseases, which comprises an effective amount of the compound as an active ingredient together with pharmaceutically acceptable inert carriers.
Preparation of Substituted N-Phenyl-4-aryl-2-pyrimidinamines as Mediator Release Inhibitors
Paul, Rolf,Hallett, William A.,Hanifin, John W.,Reich, Marvin F.,Johnson, Bernard D.,et al.
, p. 2716 - 2725 (2007/10/02)
The role of immunologically released mediators, such as histamine, leukotrienes, and platelet-activating factor, is well-established for asthma and other allergic disorders.Developing therapeutic agents which would block mediator release from mast cells and other relevant cell types would provide a rational approach to asthma therapy.Using human basophil as a screen, a series of 4-aryl-2-(phenylamino)pyrimidines was found which inhibited mediator release.These compounds were prepared by condensing acetyl heterocycles with dimethylformamide dimethyl acetal to form enaminones which are cyclized with aryl guanidines to give pyrimidines.After examining a large number of analogs, N--4-(2-pyridinyl)-2-pyrimidinamine (1-27) was chosen for toxicological evaluation.
