A Review on Uses of Combinatorial Chemistry in Drug Discovery

Review Article

Abstract

Combinatorial chemistry represents a paradigm shift in chemical synthesis methodology, enabling simultaneous generation of multiple structurally diverse compounds called libraries. The approach encompasses rapid synthesis of compound arrays through systematic combination of building blocks using solid-phase, solution-phase, parallel synthesis and split-pool techniques. Integration with high-throughput screening allows efficient identification of active compounds, significantly accelerating drug discovery timelines compared to traditional one-compound-at-a-time methods. The methodology originated from Merrifield's solid-phase peptide synthesis in the 1960s and gained widespread industrial adoption in the 1990s. Modern combinatorial approaches utilize various solid supports like polystyrene resins, sophisticated linker chemistry, and automated parallel synthesizers. The technology has revolutionized lead discovery and optimization in pharmaceutical research while finding applications in materials science, catalyst development, and chemical biology. Combinatorial libraries containing thousands of compounds can be rapidly synthesized and screened against biological targets. Key advantages include accelerated synthesis timeframes, broader structural diversity, rich structure-activity relationship data, and comprehensive patent coverage. Despite challenges in product characterization and chemistry limitations on solid phase, combinatorial chemistry continues advancing through innovations in synthetic methodology, automation, and analytical techniques. The significant impact spans multiple scientific domains including drug development, materials discovery, and chemical process optimization