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Azamacrocyclic Metal Complexes as CXCR4 Antagonists
Author(s) -
Tanaka Tomohiro,
Narumi Tetsuo,
Ozaki Taro,
Sohma Akira,
Ohashi Nami,
Hashimoto Chie,
Itotani Kyoko,
Nomura Wataru,
Murakami Tsutomu,
Yamamoto Naoki,
Tamamura Hirokazu
Publication year - 2011
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201000548
Subject(s) - cxcr4 , chemistry , chemokine receptor , cxcr4 antagonist , biological activity , g protein coupled receptor , receptor , human immunodeficiency virus (hiv) , rheumatoid arthritis , chemokine , stereochemistry , pharmacology , combinatorial chemistry , biochemistry , medicine , immunology , in vitro
The chemokine receptor CXCR4 is a member of the seven transmembrane GPCR family, which is implicated in multiple diseases, including HIV infection, cancers, and rheumatoid arthritis. Low‐molecular‐weight nonpeptidic compounds, including AMD3100 and various pyridyl macrocyclic zinc(II) complexes, have been identified as selective antagonists of CXCR4. In the present study, structure–activity relationship studies were performed by combining the common structural features of alkylamino and pyridiyl macrocyclic antagonists. Several new zinc(II) or copper(II) complexes demonstrated potent anti‐HIV activity, strong CXCR4‐binding activity, and significant inhibitory activity against Ca 2+ mobilization induced by CXCL12 stimulation. These results may prove useful in the design of novel CXCR4 antagonists, and the compounds described could potentially be developed as therapeutics against CXCR4‐relevant diseases or chemical probes to study the biological activity of CXCR4.