Good knowledge of Organic Chemistry are required, particularly regarding, synthetic methods, reactions mechanisms, and stereochemistry.

• The course consists of direct lectures, but open debate is appreciated
• PowerPoint presentations (in English) are used for the lessons
• Meetings can be fixed directly e-mailing the teacher

- 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

-  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.

- Introduction to Nanomedicine 

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

• Slides and notes of the lectures
• Literature cited during lecture (all references will be given)
• The Practice of Medicinal Chemistry (C. G. Wermuth et al, Elsevier)
• The Organic Chemistry of Drug Design and Drug Action (Silverman and Holladay, Elsevier)
• Chemistry of Bioconjugates, (Narain, Wiley)

• An oral examination will be used as assessment method
• the oral examination is normally 30-40 minutes long
• the examination consists of questions concerning the course
• candidates will be initially asked to propose design and synthesis of analogs of given molecules, as a starting point for exam questions
• At the end of the examination, the teacher will assign a score (from 18/18 to a max of 30/30 cum laude) reflecting student's degree of preparation.

http://www.sosandpepsy.org/

For the academic year 2022/2023 the course of Medicinal Chemistry will be involved in the didactic project "Il Piccolo Cimento", in collaboration with other 2 courses. More informations will be given the first day of lesson.