Chelate oxorhenium to assemble new integrin antagonists

Assembly of independent chemical modules through oxorhenium coordination by a NS2 + S chelation motif was applied to the synthesis of RGD (Arg-Gly-Asp) analogs. Modules were assembled through oxorhenium chelation to give a series of 18 metal complexes in good yields and satisfactory purities. Screening of these oxorhenium coordinates as antagonists of integrins αVβ3, αIIbβ3 and αVβ5 led to the identification of 3 bioactive compounds that exhibit submicromolar affinities for the 3 integrins. Preliminary studies showed that the corresponding oxotechnetium complexes are stable in mice plasma and therefore could be proposed for the molecular imaging of pathologies that overexpress integrins αVβ3 and αVβ5.

Complexes 11a, 12a and 12f, selected from a series of 18 oxorhenium chelates, bind to integrins αVβ3, αIIbβ3 and αVβ5 in the micro to submicromolar range.Figure optionsDownload as PowerPoint slide