Medicinal Chemistry

Principal phases of drug action (20 hours). Pharmaceutic, pharmacokinetic and pharmacodynamic phases. Pharmacokinetics: the processes of Absorption, Distribution, Metabolism, and Excretion of drugs. Pharmacodynamics: the molecular targets of drugs and the receptor concept. Structure and function of the receptors. Nature of drug-receptor interactions. Quantitative analysis of drug-receptor interactions and drug-induced biological responses (cell-free binding assays and cell-based functional assays). Definition of affinity, potency, efficacy, selectivity, therapeutic index. Definition of agonist, partial agonist, inverse agonist, antagonist. Receptor theories: models for drug-mediated receptor activation. Processes of signal transduction. Enzymes as drug targets.
Principal phases of drug discovery and development process (16 hours). Approaches for HIT and LEAD identification. Ligand efficiency metrics. LEAD modification and optimization: isostery and bioisostery, molecular simplification and complication, rigid analogs and prodrugs. Molecular modification of peptides. Recent advances in the design of peptidomimetics. Introduction to computer-aided drug design methods (CADD). Computer lab lesson on the use of structural and medchem databases.
Analysis of selected pharmacological classes to illustrate the points discussed in the general section (12 hours).