Pyridine Linked Bis Cross-bridged Tetraazamacrocycles

Abstract

Bis cross-bridged tetraazamacrocycles, and their transition metal complexes, have become one of the most effective classes of CXCR4 chemokine receptor antagonists. These cell surface receptors are important to a number of disease states, including HIV, cardiovascular disease, and cancer. Our group has continued to produce new analogues of these compounds in an effort to improve further the efficacy, specificity, and drug-like properties of this class of compounds. In this presentation, we will describe the synthesis, chemical characterization, and biological activity of a new series of bis cross-bridged tetraazamacrocyles in which the unit linking the two macrocyclic units is a nitrogen-containing pyridine, rather than the typical all carbon aromatic linking units of our previous compounds. Results include the apparent production of a 2+2 cyclic version of our typical ligands apparently driven by the change to the pyridine linker.