ACS Omega 2025 Oct 21;1041:47714-47731. doi: 10.1021/acsomega.5c06428.

Ugi and Groebke-Blackburn-Bienaymé Reactions in Medicinal Chemistry: An Outlook on New Bioactive Compounds.

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The FDA has approved 174 new molecular entities over the last 5 years. In 2023, the anticancer and infectious disease areas represented an impressive percentage of drug approvals, 24% and 9%, respectively, following the decade's trends. This reflects the pharmaceutical industry's increasing demand for novel compounds, particularly in these fields. Isocyanide-based multicomponent reactions, such as Ugi and Groebke-Blackburn-Bienaymé reactions, stand out for their versatility in obtaining different bioactive scaffolds using simpler starting materials. A large array of complex scaffold molecules can be obtained by using a multicomponent synthesis step. For this reason, this mini-review summarizes some recent works that employed this approach to afford new anticancer, antiviral, antimicrobial, and antiparasitic compounds. In each case, how the modifications impact activity or cytotoxicity is discussed. Also, the possible gaps that should be evaluated in further work are highlighted to inspire the design of new compounds.

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