Configurations and reactivity control of constrained macrocycles -

CXCR4 chemokine receptors are found on the surface of immune cells, and together with the specific natural ligand CXCL12 have been revealed to play a role in a number of disease states. For example, the CXCR4CXCL12 signalling system has involvement in cancer progression and metastasis, and the development of rheumatoid arthritis. Also, within the last ten years the CXCR4 and CCR5 co-receptors have been revealed as the entry route for HIV into cells, generating interest in a new therapeutic approach to treatment via entry inhibitor drugs rather than the current preference for reverse transcriptase and protease inhibitors. Our aim is to synthesise new antagonists for the CXCR4 coreceptor. They are configurationally fixed macrocyclic compounds where the unrestrained equivalent is a known CXCR4 antagonist. We are attempting to gain further insights into the essential design features for this drug class through computational, spectroscopic and biological studies [2]. 2.Novel radiopharmaceutical constructs incorporating macrocycles