Styryl Group, a Friend or Foe in Medicinal Chemistry

The styryl (Ph-CH=CH-R) group is widely represented in medicinally important compounds, including drugs, clinical candidates, and molecular probes as it positively impacts the lipophilicity, oral absorption, and biological activity. The analysis of matched molecular pairs (styryl vs. phenethyl, phenyl, methyl, H) for the biological activity indicates the superiority aspect of styryl compounds. However, the Michael acceptor site in the styryl group makes it amenable to the nucleophilic attack by biological nucleophiles and transformation to the toxic metabolites. One of the downsides of styryl compounds is isomerization that impacts the molecular conformation and directly affects biological activity. The impact of cis-trans isomerism and isosteric replacements on biological activity is exemplified. We also discuss the styryl group-bearing drugs, clinical candidates, and fluorescent probes. Overall, the present review reveals the utility of the styryl group in medicinal chemistry and drug discovery.