- The Practice of Medicinal Chemistry di Camille Georges Wermuth
- The Organic Chemistry of Drug Design and Drug Action di Richard Bruce Silverman



- Introduction on the contents and objectives of the course. Books suggested, and mode of examination. - Nomenclature in Med Chem - Drug activity phases into the body - Drug Classification Systems - Strategies in the search for new lead compounds: Analog Design, Systematic screening, Explotaion of biological informations, Planned research and rational design

- Primary Structure Activity - Topological exploration of lead compounds - Reasoning by functionalities - Application Rules - Isosterism: Hystory & Definitions - Ring equivalents - Bioisosters of Pyridine, Pyridazine, Oxazolidinone, Carboxylic acid derivatives, carboxiamides, Urea and Thiourea derivatives, phenol functions and halogens

- Ring Transormations using: Analogical approach, Disjunctive or Conjunctive approach. - Imprtance of Macrocycles in Med Chem - History, Importance and Use of Combinatorial Chemistry in the discovery and development of new drugs - Methods and Techniques: Splity and Mix libraries; Houghton's Tea bag method;Parallel Synthesis - Reading and Interpretation of Combi libraries: Deconvolution methods; Encoding and Tagging methods. - Multicomponent Reactions: Strecker, Bigginelli, Passerini Ugi reactions - Bioconjugation methods useful for Combi Chem: Reductive amination; Morita-Baylis-Hillman reaction; S-alkylation; Native Chemical Ligation; Click Chemistry - Bio-orthogonal reactions; Copper-free click chemistry

- Origin and characteristics of aminoacids, importance and functions of peptides in medicinal chemistry, petidic synthesis in solid phase and liquid phase, coupling reagents, protecting group strategies - Dynamic Combinatorial Chemistry: Hystory and application in Med Chem. - Exchange reactions used in DCLs - Development of synthetic receptors and ligands for biomolecules using DCLs - Different strategies to find ligands for biomolecules in DCLs: Stoichiometric DCLs, Post-modified DCLs, Pre-equilibrated and itered DCLs, Tethering approach, In situ Click approach

- Optical isomerism in drugs, three-point contact model, definition of Eutomers, Distomers and Eudismic quotient/index. Pfeiffer's rule and practical considerations on chirality on drugs. - Solubilizing moieties: acidic solubilizing chains, basic solubilizing chains, non-ionizible solubilizing chains. - Short overview on System Chemistry to conclude the discussion on Combi Chem. Self-replicator systems, Asymmetric Autocatalysis.

- QSAR Quantitative Structure-Activity Relationship; - Electronic effects: The Hammett equation - Lipophilic effects: The Hansch equation - Steric effects: The Taft equation; Molar refractivity and Verloop parameters - Influence of Substituent groups on Lead molecules: Methyl substitution effects on solubility, lipophilicity, crystal lattice cohesion, conformational constrain, metabolism Effects of Vinyl and Allylic substituent groups, N-Allyl derivatives, Acetylenic groups - Effects of Halogenation - Effects of Hydroxylation

- Drug Delivery Systems General techniques of Pharmaceutical preparations: Passive, pre-regulated delivery sysyems. Active self-regulated delivery systems. - Main mechanisms to control drug the drug release: Dissolution, Partitioning, Diffusion, Osmosis, Swelling, Erosion, Targeting.

- Exercises in the class-room based on real case studies. Students proposed solutions for Drug-Design issues, Med Chem strategies. SAR studies.