Recent developments with rhodanine as a scaffold for drug discovery

Area of Science:

• Medicinal Chemistry
• Organic Chemistry
• Drug Discovery

Background:

• Rhodanines, a subtype of 4-thiazolidinones, are privileged heterocycles in medicinal chemistry.
• They have led to drug-like molecules with diverse biological activities and approved drugs.
• 5-ene-rhodanines are notable for their Michael acceptor functionality, sometimes leading to claims of pan assay interference.

Purpose of the Study:

• To review synthetic protocols for rhodanines and their transformations.
• To discuss biological activities, biotargets, modes of action, and optimization strategies.
• To explore the use of 5-ene-rhodanines in Michael additions, presenting arguments for and against their medicinal chemistry applications.

Main Methods:

• Review of synthetic protocols for rhodanines and their derivatives.
• Discussion of biological activities and target interactions.
• Analysis of 5-ene-rhodanines in the context of Michael addition reactions.

Main Results:

• Rhodanines are accessible building blocks for creating related heterocycles and analogues.
• The potential for low selectivity of rhodanines due to Michael acceptor functionality requires experimental confirmation.
• Positive aspects of Michael acceptors, including multitarget properties, should be considered.

Conclusions:

• Rhodanines remain privileged scaffolds in drug discovery.
• Experimental validation is crucial for assessing rhopdaine selectivity concerns.
• Rhodanines are generally not problematic per se in drug development.