Gao, Mingshan; Duan, Lei; Luo, Jinfeng; Zhang, Lianwen; Lu, Xiaoyun; Zhang, Yan; Zhang, Zhang; Tu, Zhengchao; Xu, Yong; Ren, Xiaomei; Ding, Ke published the artcile< Discovery and Optimization of 3-(2-(Pyrazolo[1,5-a]pyrimidin-6-yl)ethynyl)benzamides as Novel Selective and Orally Bioavailable Discoidin Domain Receptor 1 (DDR1) Inhibitors>, Safety of 3-Chloro-5-methylaniline, the main research area is pyrazolopyrimidinylethynylbenzamide preparation discoidin domain receptor 1 inhibitor; antitumor activity pharmacokinetics pyrazolopyrimidine substituted ethynylbenzamide.
Discoidin domain receptor 1 (DDR1) is an emerging potential mol. target for new anticancer drug discovery. The authors have discovered a series of 3-(2-(pyrazolo[1,5-a]pyrimidin-6-yl) ethynyl)benzamides that are selective and orally bioavailable DDR1 inhibitors. The two most promising compounds (I and II) inhibited the enzymic activity of DDR1, with IC50 values of 6.8 and 7.0 nM, resp., but were significantly less potent in suppressing the kinase activities of DDR2, Bcr-Abl, and c-Kit. Further study revealed that I bound with DDR1 with a Kd value of 0.6 nM, while it was significantly less potent to the other 455 kinases tested. The S(35) and S(10) selectivity scores of I were 0.035 and 0.008, resp. The compounds also potently inhibited the proliferation of cancer cells expressing high levels of DDR1 and strongly suppressed cancer cell invasion, adhesion, and tumorigenicity. Preliminary pharmacokinetic studies suggested that they possessed good PK profiles, with oral bioavailabilities of 67.4% and 56.2%, resp.
Journal of Medicinal Chemistry published new progress about Antitumor agents. 29027-20-1 belongs to class chlorides-buliding-blocks, and the molecular formula is C7H8ClN, Safety of 3-Chloro-5-methylaniline.
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Chlorides – an overview | ScienceDirect Topics