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doi: 10.1001/jama.2011.1471 253 MunshiLWalkeyAGoligherEPhamTUlerykEMFanE

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To view or add a comment, sign in More Relevant Posts STRUCTUREACTIVITY RELATIONSHIPS (SAR) Where chemistry defines clinical effect Small structural changes major pharmacologic outcomes Functional groups Hydrogen bonding & ionic interactions or potency Stereochemistry Enantiomers differ in efficacy, safety, and metabolism Lipophilicity (logP) Controls membrane penetration, tissue distribution, CNS access pKa & ionization Determines absorption, bioavailability, and receptor binding Ring systems & rigidity Influence receptor selectivity and intrinsic activity Metabolic hotspots Steric shielding reduces CYP metabolism half-life Key insight: Clinical response begins at the molecular level dose optimization starts with structure optimization