42106-50-3Relevant academic research and scientific papers
Discovery of novel 2-phenylamino-4-prolylpyrimidine derivatives as TRK/ALK dual inhibitors with promising antitumor effects
Cao, Zhi,Guo, Ming,Jiang, Nan,Li, Changtao,Li, Tong,Wang, Xinyu,Yang, Jing,Zhai, Xin
, (2021/10/06)
In order to explore novel TRK and ALK dual inhibitors, a series of 2-phenylamino-4-prolylpyrimidine derivatives were designed, synthesized and evaluated for their in vitro cytotoxicity and enzymatic activities. Delightfully, most compounds were detected m
Discovery of novel N-benzylbenzamide derivatives as tubulin polymerization inhibitors with potent antitumor activities
Zhu, Huajian,Li, Wenlong,Shuai, Wen,Liu, Yang,Yang, Limei,Tan, Yuchen,Zheng, Tiandong,Yao, Hong,Xu, Jinyi,Zhu, Zheying,Yang, Dong-Hua,Chen, Zhe-Sheng,Xu, Shengtao
, (2021/03/08)
A series of novel N-benzylbenzamide derivatives were designed and synthesized as tubulin polymerization inhibitors. Among fifty-one target compounds, compound 20b exhibited significant antiproliferative activities with IC50 values ranging from 12 to 27 nM against several cancer cell lines, and possessed good plasma stability and satisfactory physicochemical properties. Mechanism studies demonstrated that 20b bound to the colchicine binding site and displayed potent anti-vascular activity. Notably, the corresponding disodium phosphate 20b-P exhibited an excellent safety profile with the LD50 value of 599.7 mg/kg (i.v. injection), meanwhile, it significantly inhibited tumor growth and decreased microvessel density in liver cancer cell H22 allograft mouse model without obvious toxicity. Collectively, 20b and 20b-P are novel promising anti-tubulin agents with more druggable properties and deserve to be further investigated for cancer therapy.
Discovery of 4-benzoylpiperidine and 3-(piperidin-4-yl)benzo[d]isoxazole derivatives as potential and selective GlyT1 inhibitors
Liu, Yang,Guo, Lin,Duan, Hongliang,Zhang, Liming,Jiang, Neng,Zhen, Xuechu,Shen, Jianhua
, p. 40964 - 40977 (2015/05/20)
Regulation of glycine transporter 1 (GlyT1) activity is a currently investigated strategy in drug discovery for schizophrenia. This study developed a series of new 4-benzoylpiperidine derivatives as GlyT1 inhibitors by bioisosteric replacement and mimicking of the pyridine ring of RG1678. Among the 4-benzoylpiperidine derivatives, 23q showed an IC50 of 30 nM. Preliminary optimization of the blood-brain barrier penetration led to the discovery of 3-(piperidin-4-yl)benzo[d]isoxazole derivatives. Both series showed good selectivity over GlyT2, D1, D2, D3, 5-HT1A and 5-HT2A receptors. Moreover, behavioral testing showed 23q (40 mg kg-1, intragastric) can inhibit the hyperlocomotion induced by acute treatment of phencyclidine, and improve the impaired negative and cognitive symptoms in chronic phencyclidine-induced C57BL/6J mice. An interesting finding showed that 3-(piperidin-4-yl)benzo[d]isoxazole was a privileged scaffold of atypical antipsychotic agents but exhibited high selectivity and potency as a GlyT1 inhibitor.
Ultrasound-promoted reaction of 2-chlorobenzoic acids and aliphatic amines
Docampo, Maite L.,Pellon, Rolando F.,Estevez-Braun, Ana,Ravelo, Angel G.
, p. 4111 - 4115 (2008/02/13)
An improvement to the use of DMF as a solvent for the condensation of 2-chlorobenzoic acids with aliphatic primary or secondary amines was described. A number of alkylaminobenzoic acids and dialkylaminobenzoic acids were synthesized in acceptable-to-good yield. The advantages of this procedure include readily available substrates, the use of an inexpensive copper powder without taking any precautions to exclude moisture under mild conditions and experimental ease. Furthermore, this condensation could also be achieved under nonclassical conditions by using ultrasonic irradiation at room temperature. We demonstrated that ultrasound-promoted condensation of 2-chlorobenzoic acid with aliphatic amines with the use of DMF as the solvent, especially in the case of secondary amines, affords products in high yields and reduces the reaction time to minutes. The results proved to be highly reproducible because the relevant sonochemical parameters were rigorously controlled. Wiley-VCH Verlag GmbH & Co. KGaA, 2007.
