27519-68-2Relevant academic research and scientific papers
Synthesis, biological evaluation and molecular modeling study of 2-amino-3,5-disubstituted-pyrazines as Aurora kinases inhibitors
Bo, Yong-Xin,Chen, Shi-Wu,Hao, Shu-Yi,Wang, Xing-Rong,Xiang, Rong,Xu, Yu
, (2020/02/11)
Serine/threonine protein kinases Aurora A, B, and C play essential roles in cell mitosis and cytokinesis, and a number of Aurora kinase inhibitors have been evaluated in the clinic. Herein we report the synthesis and their antiproliferation of 3,5-disubstituted-2-aminopyrazines as kinases inhibitors. Amongst, 4-((3-amino-6- (3,5-dimethylisoxazol-4-yl)pyrazin-2-yl)oxy)-N-(3-chlorophenyl) benzamide (12Aj) exhibited the strongest antiproliferative activities against U38, HeLa, HepG2 and LoVo cells with IC50 values were 11.5 ± 3.2, 1.34 ± 0.23, 7.30 ± 1.56 and 1.64 ± 0.48 μM, as well as inhibited Aurora A and B with the IC50 values were 90 and 152 nM, respectively. Molecular docking studies indicated that 12Aj appeared to form stable hydrogen bonds with either Aurora A or Aurora B. Furthermore, 12Aj arrested HeLa cell cycle in G2/M phase by regulating protein levels of cyclinB1 and cdc2. In addition, the bioinformatics prediction further revealed that 12Aj possessed good drug likeness using SwissADME. These results suggested that 12Aj was worthy of future development of potent anticancer agents as pan-Aurora kinases.
Methyl-triflate-mediated dearylmethylation of: N -(arylmethyl)carboxamides via the retro-Mannich reaction induced by electrophilic dearomatization/rearomatization in an aqueous medium at room temperature
Peng, Hui,Ma, Jinhui,Luo, Wenkun,Zhang, Guangwen,Yin, Biaolin
supporting information, p. 2252 - 2256 (2019/05/17)
We have developed a protocol for the dearylmethylation of N-(arylmethyl)carboxamides under metal-free conditions in an aqueous medium at room temperature. This protocol involves methyl triflate-mediated successive C-C and C-N bond cleavages (retro-Mannich reaction) induced by electrophilic dearomatization/rearomatization. The dearomatization/rearomatization strategy can be expected to inspire the development of novel transformations based on the C-C bond cleavage in an environmentally benign manner.
3,5-disubsitutued 2-amino-pyrazine compound and preparation technology and application thereof
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Paragraph 023; 0024; 0025, (2018/07/30)
The invention discloses a 3,5-disubsitutued 2-amino-pyrazine compound. The compound has the structure shown in the formula I; in the formula I, NR1R2 is n-propylamino, cyclopropylamino, cyclopentylamino, cyclohexylamino, morpholinyl, 4-methyl piperazine, anilino, 4-chloroaniline or 3-chloroaniline; Ar is 3,5-dimethyl-isoxazolyl-4 or 1-methyl-1H-pyrazolyl-4; and the invention further provides the preparation technology and application thereof. The compound has the outstanding inhibiting effect on growth of four kinds of cancer cells including a human cervical cancer cell HeLa, a human brain glioma cell U87, a human hepatoma cancer cell HepG2 and a human colon cancer cell LoVo, wherein a large part of the compound has an obviously higher inhibiting effect on proliferation of the cancer cellsthan positive control VX-680, particularly the compound Ih and Ii have relatively high activity on the four kinds of cancer cells, and have prominent activity inhibiting effect on aurora kinase A andaurora kinase B, and therefore the compound can be applied to preparation of anti-cancer drugs.
On the intractability of estrogen-related receptor α as a target for activation by small molecules
Hyatt, Stephen M.,Lockamy, Elizabeth L.,Stein, Rebecca A.,McDonnell, Donald P.,Miller, Aaron B.,Orband-Miller, Lisa A.,Willson, Timothy M.,Zuercher, William J.
, p. 6722 - 6724 (2008/09/17)
The estrogen-related receptor α (ERRα) is a potential target for activation in the treatment of metabolic disease. To date, no small-molecule agonists of ERRα have been identified despite several high-throughput screening campaigns. We describe the synthesis and profiling of a small array of compounds designed on the basis of a previously reported agonist-bound crystal structure of the closely related receptor ERRγ. The results suggest that ERRα may be intractable as a direct target for pharmacologic activation.
Serine peptidase modulators
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, (2008/06/13)
The present invention relates to new compounds having modulatory (inhibitory and stimulatory) activity on serine peptidases and proteases in general and dipeptidyl peptidase IV, prolyl oligopeptidase (PO), dipeptidyl peptidase II (DPP II), fibroblast activation protein α (FAPα), lysosomal Pro—X carboxypeptidase and elastase in particular. These new compounds can be used for the treatment of a variety of disease states in which these peptidases are involved.
Structure-activity relationship of diaryl phosphonate esters as potent irreversible dipeptidyl peptidase IV inhibitors.
Belayev, Alexander,Zhang, Xuemei,Augustyns, Koen,Lambeir, Anne-Marie,Meester, Ingrid De,et al.
, p. 1041 - 1052 (2007/10/03)
The previously reported diphenyl 1-(S)-prolylpyrrolidine-2(R, S)-phosphonate (5) was used as a lead compound for the development of potent and irreversible inhibitors of dipeptidyl peptidase IV (DPP IV, EC 3.4.14.5). The synthesis of a series of diaryl 1-
