Chiral-First Design
Definition: A molecular design philosophy in which chirality is considered a primary design parameter from the earliest stages of discovery, rather than an afterthought addressed during optimization or development.
Context: Chiral-first design integrates stereochemistry into target selection, ligand design, synthesis planning, and biological evaluation. This approach reduces downstream risk, avoids late-stage chiral switches, and improves alignment between chemical structure and biological function.
Example: Designing a kinase inhibitor library around a defined axial chirality scaffold instead of screening racemic mixtures and resolving later.
Related Terms: Chiral Intelligence; Stereo-pharmacology; Enantioselective Synthesis; Drug Design Strategy
Reference: Ariens, E. J., Stereochemistry, a basis for sophisticated nonsense in pharmacokinetics and clinical pharmacology, European Journal of Clinical Pharmacology, 26, 663-668, (1984)
DOI: 10.1007/BF00541922
FDA Guidance for Industry (1992) Development of New Stereoisomeric Drugs
Establishes the requirement to maintain, characterize, and justify stereochemical integrity throughout development - a direct institutional basis for chiral fidelity.