The synthesis of novel CXCR4 antagonists for use in oncology and molecular imaging

The CXC chemokine receptor 4 (CXCR4) is a G protein-coupled receptor (GPCR), that plays an essential role in primary tumor growth, cancer cell migration, and the establishment of metastatic sites. The promise of CXCR4 as an oncology drug target stimulated the search for CXCR4 antagonists. Although tetrahydroquinolinebasedCXCR4 antagonists have been studied extensively, the understanding of their structure-activity relationship (SAR) is still incomplete. In this grant proposal, the SAR of this class of compounds will be further evaluated by the synthesis of novel structures, based on previously generated biological data. In addition, this type of chemistry will also be used for the synthesis of imaging probes that allow for the in vivo detection of CXCR4 expression.

Keywords:CXCR4, antagonist, heterocyclic chemistry

Disciplines:Organic chemical synthesis, (Bio)molecular modelling and design