Late-stage modification of bioactive compounds: Improving druggability through efficient molecular editing

Area of Science:

• Medicinal Chemistry
• Organic Synthesis
• Drug Discovery

Background:

• Synthetic chemistry is crucial for identifying, optimizing, and preparing drug candidates.
• Late-stage functionalization of bioactive compounds offers a rapid route to chemical diversity.
• Modifications alter chemical space, physicochemical properties, potency, and druggability.

Purpose of the Study:

• To review recent advances (last two decades) in late-stage modification for drug discovery.
• To focus on the incorporation of halogen, oxygen, and nitrogen elements.
• To discuss current challenges and future directions in the field.

Main Methods:

• Review of literature on late-stage functionalization techniques.
• Analysis of methods for introducing halogens, oxygen, and nitrogen into drug scaffolds.
• Discussion of the impact of these modifications on compound properties.

Main Results:

• Significant progress has been made in late-stage modification strategies over the past 20 years.
• Methods for incorporating halogens, oxygen, and nitrogen are increasingly sophisticated.
• These modifications can effectively tune the properties of drug candidates.

Conclusions:

• Late-stage modification is a powerful strategy for generating novel drug-like molecules.
• Enhanced collaboration between chemists and pharmacists can accelerate the discovery of new activities.
• This review provides a resource for applying late-stage modification in drug design.