94694-53-8Relevant academic research and scientific papers
Design, Synthesis, and Characterization of Novel CXCR4 Antagonists Featuring Cyclic Amines
Fu, Chunyan,He, Sudan,Li, Zhanhui,Lin, Yu,Luo, Lusong,Ma, Haikuo,Song, Shiwei,Tian, Sheng,Wang, Xu,Wang, Yujie,Wu, Shuwei,Zhang, Xiaohu,Zhao, Li,Zheng, Jiyue,Zhu, Fang
, (2020/06/01)
Chemokine receptor CXCR4 and its natural ligand CXCL12 (also known as stromal cell-derived factor-1, or SDF-1) regulate a broad range of physiological functions. Dysregulation of the CXCL12/CXCR4 axis is involved in numerous pathological conditions such as HIV infection, inflammation and cancer. Herein, we report the design, synthesis, and characterization of novel CXCR4 antagonists based on cyclic amine scaffolds. Compound 24 was identified as a potent CXCR4 receptor antagonist (competitive inhibition of 12G5 binding, IC50=24 nM; functional inhibition of CXCL12-induced cytosolic calcium increase, IC50=0.1 nM). In addition, compound 24 potently inhibited cell migration in CXCR4/CXCL12-mediated chemotaxis in a matrigel invasion assay. The absolute configuration of compound 24 was elucidated by X-ray crystallography.
Design, synthesis, and evaluation of novel CXCR4 antagonists based on an aminoquinoline template
Hao, Yongjin,He, Sudan,Li, Zhanhui,Lin, Yu,Luo, Lusong,Ma, Haikuo,Wu, Shuwei,Xia, Kaijiang,Xu, Chen,Yang, Qing,Zhang, Xiaohu,Zheng, Jiyue,Zhu, Fang
, (2020/04/23)
The chemokine receptor CXCR4 has been explored as a drug target due to its involvement in pathological conditions such as HIV infection and cancer metastasis. Here we report the structure–activity relationship study of novel CXCR4 antagonists based on an aminoquinoline template. This template is devoid of the chiral center in the classical tetrahydroquinoline (THQ) ring moiety and therefore can be easily synthesized. A number of potent CXCR4 antagonists were identified, exemplified by compound 3, which demonstrated excellent binding affinity with CXCR4 receptor (IC50 = 57 nM) and inhibited CXCL12 induced cytosolic calcium increase (IC50 = 0.24 nM). Furthermore, compound 3 potently inhibited CXLC12/CXCR4 mediated cell migration in a transwell invasion assay. The simplified synthetic approach combined with good physicochemical properties (e.g. MW 362, clogP 2.1, PSA 48, pKa 7.0 for compound 3) demonstrate the potential of this aminoquinoline template as a novel scaffold to develop CXCR4 antagonists.
HETEROARYL COMPOUNDS AS CXCR4 INHIBITORS, COMPOSITION AND METHOD USING THE SAME
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Paragraph 00181-00182; 00184, (2019/04/16)
The present disclosure provides heteroaryl compounds of Formula (I), processes for their preparation, pharmaceutical compositions containing them, and their use in the treatment of diseases and disorders, arising from or related to the CXCR4 pathway.
Substituted imidazo[1,5-c]pyrimidines
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, (2008/06/13)
Substituted imidazo[1,5-c]pyrimidines have been found to have potent bronchodilator activity. Pharmacological methods, pharmaceutical compositions and synthetic intermediates are also disclosed.
