A(3)- and A(2)B-nitrocorroles: synthesis and antiviral activity evaluation against human cytomegalovirus infection

Human cytomegalovirus (hCMV) is responsible for several pathologies impacting immunocompromised patients and can trigger life-threatening infection. Several antivirals are available and are used in the clinic, but hCMV resistant strains have appeared and patients have encountered therapeutic failure. Hence, there is a constant need for new best in class or first in class antiviral molecules. We have previously shown that nitrocorroles could be used as a potent anti-hCMV agent without acute toxicity in mice. They therefore represent an excellent platform to perform structure-activity relationship (SAR) studies and to increase efficiency or reduce toxicity. We have generated original A(2)B- and A(3)-substituted nitrocorroles and have discovered optimized compounds with selectivity indices above 200. These compounds are easily synthesized in only one to two-step reactions; they are up-scalable and cost efficient. They are therefore excellent candidates for hCMV therapies and they pave the way for a new generation of molecules.