Importance of Physicochemical Properties In Drug Discovery. (Review Article)
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Drug discovery is a complex and demanding enterprise. In recent years there has been a significant discussion on discovery and developmental processes for new chemical entities, wherein various parameters like PK, toxicity, solubility, stability are addressed. The, 'Rule of Five', gained wide acceptance as an approach to reduce attrition in drug discovery and development. However, analysis of recent trends reveals that the physical properties of molecules that are currently being synthesized in leading drug discovery companies differ significantly from those of recently discovered oral drugs and compounds in clinical development. The consequences of the marked deviation in the physicochemical properties result in a greater likelihood of lack of selectivity and attrition in drug development. Tackling the threat of compound-related toxicological attrition needs to move to the mainstream of medicinal chemistry decision-making. The impacts of these rules on oral absorption are discussed, and approaches are suggested for the prediction, assessment and communication,of,absorption-related, physicochemical properties in drug discovery and exploratory development. This review is based on how physicochemical properties of compounds can be optimized for drug discovery.
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