Medicinal Chemistry

1. Stereochemistry in Drug Design
   1. Importance of Stereochemistry
      1. Influence on pharmacological activity
      2. Implications for drug safety and efficacy
      3. Regulatory considerations for enantiomerically pure drugs
   2. Chirality and Its Effect on Drug Activity
      1. Distinction between enantiomers and diastereomers
      2. Role in drug-receptor interactions
      3. Case studies of chiral drugs with differing activities
         1. Thalidomide
         2. Naproxen
   3. Enantiomeric Purity
      1. Methods for assessing enantiomeric excess
         1. Chromatographic techniques
         2. Spectroscopic analysis
      2. Importance in quality control and regulatory compliance
   4. Pharmacokinetic Implications
      1. Stereochemistry and absorption processes
         1. Impact on bioavailability
         2. Influence on transport proteins and channels
      2. Metabolism and stereochemistry
         1. Enzymatic specificity for chiral molecules
         2. Differential metabolic pathways for each enantiomer
      3. Distribution and stereochemistry
         1. Tissue selectivity based on stereoisomeric form
         2. Binding affinity variations in plasma proteins
      4. Excretion and stereochemistry
         1. Renal clearance differences among enantiomers
         2. Biliary excretion considerations
   5. Pharmacodynamic Implications
      1. Stereoselective interaction with biological targets
         1. Receptor binding site specificity
         2. Stereochemistry in signal transduction pathway modulation
      2. Efficacy and potency of chiral drugs
         1. Dose-response variability for enantiomers
         2. Therapeutic index considerations
      3. Stereoselective side effects
         1. Unwanted actions of "inactive" enantiomers
         2. Mechanisms of adverse effects linked to stereochemistry
   6. Techniques for Stereochemical Manipulation
      1. Asymmetric synthesis methods
         1. Chiral catalysts and reagents
         2. Use of stereoselective synthesis in drug development
      2. Resolution of racemic mixtures
         1. Methods like crystallization and chiral chromatography
         2. Advances in enzymatic resolution
      3. Use of prodrugs to improve stereochemical outcomes
         1. Strategy for reducing interconversion of stereoisomers
   7. Regulatory and Ethical Considerations
      1. FDA and EMA guidelines for chiral drug products
      2. Ethical considerations in marketing and labeling stereochemically distinct drugs
      3. Implications of stereochemistry in pharmaceutical patenting
   8. Case Studies in Stereochemistry Impact
      1. Analysis of pharmaceuticals improved through stereochemistry
         1. Drugs that have benefited from stereochemical optimization
         2. Biopharmaceutical advancements attributed to stereochemistry
   9. Future Directions in Stereochemistry
      1. Integration of novel stereospecific technologies
         1. Advances in computational approaches for stereochemistry
         2. High-throughput screening methods for stereoisomers
      2. Exploration of chiral drug combinations
         1. Synergistic effects of enantiomer pairs
         2. Development of isomerically pure drug cocktails