352549-46-3Relevant academic research and scientific papers
PEPTIDE AND SMALL MOLECULE AGONISTS OF EPHA AND THEIR USES
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Paragraph 00229; 00274, (2019/01/21)
A method of treating cancer in a subject includes administering to the subject a therapeutically effective amount of a compound, the small molecule having a general formula: A-L-X-Z (I).
Design and synthesis of small molecule agonists of EphA2 receptor
Petty, Aaron,Idippily, Nethrie,Bobba, Viharika,Geldenhuys, Werner J.,Zhong, Bo,Su, Bin,Wang, Bingcheng
, p. 1261 - 1276 (2017/11/27)
Ligand-independent activation of EphA2 receptor kinase promotes cancer metastasis and invasion. Activating EphA2 receptor tyrosine kinase with small molecule agonist is a novel strategy to treat EphA2 overexpressing cancer. In this study, we performed a lead optimization of a small molecule Doxazosin that was identified as an EphA2 receptor agonist. 33 new analogs were developed and evaluated; a structure?activity relationship was summarized based on the EphA2 activation of these derivatives. Two new derivative compounds 24 and 27 showed much improved activity compared to Doxazosin. Compound 24 possesses a bulky amide moiety, and compound 27 has a dimeric structure that is very different to the parental compound. Compound 27 with a twelve-carbon linker of the dimer activated the kinase and induced receptor internalization and cell death with the best potency. Another dimer with a six-carbon linker has significantly reduced potency compared to the dimer with a longer linker, suggesting that the length of the linker is critical for the activity of the dimeric agonist. To explore the receptor binding characteristics of the new molecules, we applied a docking study to examine how the small molecule binds to the EphA2 receptor. The results reveal that compounds 24 and 27 form more hydrogen bonds to EphA2 than Doxazosin, suggesting that they may have higher binding affinity to the receptor.
Quinazoline derivatives, composition and application thereof
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Paragraph 0105; 0106, (2018/07/06)
The invention relates to quinazoline derivatives as shown in a formula I as described in the specification, a composition and application thereof as a PGK1 inhibitor for preparing anti-tumor drugs andapplication thereof in treating malignant tumors.
Discovery of potent CCR4 antagonists: Synthesis and structure-activity relationship study of 2,4-diaminoquinazolines
Yokoyama, Kazuhiro,Ishikawa, Noriko,Igarashi, Susumu,Kawano, Noriyuki,Hattori, Kazuyuki,Miyazaki, Takahiro,Ogino, Shin-ichi,Matsumoto, Yuzo,Takeuchi, Makoto,Ohta, Mitsuaki
, p. 7021 - 7032 (2008/12/22)
A new series of quinazolines that function as CCR4 antagonists were discovered during the screening of our corporate compound libraries. Subsequent compound optimization elucidated the structure-activity relationships and led the identification of 2-(1,4′-bipiperidine-1′-yl)-N-cycloheptyl-6,7-dimethoxyquinazolin-4-amine 14a, which showed potent inhibition in the [35S]GTPγS-binding assay (IC50 = 18 nM). This compound also inhibited the chemotaxis of human and mouse CCR4-expressing cells (IC50 = 140 nM, 39 nM).
