Drug evolution: p-aminobenzoic acid as a building block

Area of Science:

• Medicinal Chemistry
• Drug Discovery
• Organic Chemistry

Background:

• The core structure, or building block, is crucial in developing new drugs.
• p-aminobenzoic acid (PABA) is a frequently observed structural motif in existing pharmaceuticals.

Purpose of the Study:

• To review p-aminobenzoic acid (PABA) as a valuable building block for designing novel drugs or drug candidates.
• To analyze the therapeutic applications and structural diversity of PABA-containing drugs.

Main Methods:

• Database analysis of 12,111 commercial drugs to identify PABA-containing compounds.
• Review of molecular targets and mechanisms of action for PABA-based drugs.
• Analysis of structural diversity, including substitutions at various positions of the PABA moiety.

Main Results:

• 184 commercial drugs (1.5%) contain the PABA moiety, exhibiting a wide range of therapeutic uses.
• Significant structural diversity was observed in PABA-containing drugs, with numerous substitutions possible at the amino, carboxyl, and aromatic ring positions.
• PABA's structure is amenable to combinatorial library generation, with potential to create over 4.5 million compounds.

Conclusions:

• p-aminobenzoic acid (PABA) is a highly adaptable and valuable building block for drug discovery.
• The structural versatility of PABA supports the creation of diverse chemical libraries for identifying new drug-like molecules.
• PABA's prevalence and adaptability make it a key component in the design of pharmaceuticals with broad therapeutic potential.