Design, Synthesis, and Characterization of Novel CXCR4 Antagonists Featuring Cyclic Amines.

Design, Synthesis, and Characterization of Novel CXCR4 Antagonists Featuring Cyclic Amines.
ChemMedChem. 2020 May 11;:
Authors: Zhang X, Lin Y, Li Z, Ma H, Wang Y, Wang X, Song S, Zhao L, Wu S, Tian S, Fu C, Luo L, Zhu F, He S, Zheng J
Abstract
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, IC 50 = 24 nM; functional inhibition of CXCL12 induced cytosolic calcium increase, IC 50 = 0.1 nM). In addition, compound 24 potently inhibited cell migration in the CXCR4/CXCL12 mediated chemotaxis in a matrigel invasion assay. The absolute configuration of compound 24 was elucidated by X-ray crystallography.
PMID: 32391652 [PubMed - as supplied by publisher]

Source: ChemMedChem - May 10, 2020 Category: Chemistry Authors: Zhang X, Lin Y, Li Z, Ma H, Wang Y, Wang X, Song S, Zhao L, Wu S, Tian S, Fu C, Luo L, Zhu F, He S, Zheng J Tags: ChemMedChem Source Type: research