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

## TL;DR

This paper reviews recent uses of Ugi and Groebke–Blackburn–Bienaymé reactions to create new bioactive compounds for drug development.

## Contribution

The paper highlights the versatility of isocyanide-based reactions in generating diverse bioactive scaffolds for medicinal chemistry.

## Key findings

- Ugi and Groebke–Blackburn–Bienaymé reactions are effective for synthesizing complex drug-like molecules from simple precursors.
- Recent studies show these reactions can produce anticancer, antiviral, antimicrobial, and antiparasitic compounds.
- Modifications to these compounds impact their biological activity and cytotoxicity.

## Abstract

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.