Catalogo dei Corsi di studio

This course provides the students with the theoretical knowledge and technical skills and introduce them to the structure and properties of pharmaceutical agents and metabolites. The course outlines the structure, bonding and chemical reactivity of various important classes of organic molecules, ranging from simpler examples of hydrocarbons or those containing a single functional group, to some of the important biological molecules such as carbohydrates, nucleic acids and proteins. Topics include basic concepts in medicinal chemistry: 1) the drug discovery and development process, 2) review of organic functional groups found in drug molecules, 3) drug-target interactions, 4) physicochemical properties related to drug action such as acid-base properties, equilibrium, and stereochemistry, 5) Effect of chemical structure on the metabolism of drug molecules.
By completing Pharmaceutical Chemistry, the student acquires:
1. Recognize and describe zero-, first- and second-order kinetics, perform elementary calculations of rate constants and appreciate the role of enzymes in catalysis.
2. Integrate knowledge from foundational sciences to explain how specific drugs or drug classes work and evaluate their potential value in individuals and populations.
3. Apply knowledge in foundational sciences to solve therapeutic problems.
4. Demonstrate an understanding of the therapeutic potential of a candidate molecule and how chemical properties can affect its potential to become a new drug.

Programma

This course will cover the following topics, which will be also discussed through case studies and evaluation of scientific publications, focusing on research methodology.
- Chemical aspects of drug metabolism: introduction, effects of chemical structure on Phase I oxidative, reductive, and hydrolytic reactions, effects of chemical structure on phase II conjugative reactions (COMT and PNMT-catalyzed methylation, acetylation, sulfation, glucuronidation, amino acid conjugation, mercapturic acid formation), sites of metabolism, metabolic pathways of selected common drugs.
- Hit identification: overview of the drug discovery process; target-based, systems-based and chemocentric drug discovery; de novo drug design vs screening (virtual screening, random screening, high throughput screening); guiding principles and challenges in target-based and phenotypic drug discovery; chemical probes; compound sources for chemical libraries and focused compound collections; fragment-based drug discovery (principles, fragment-based screening, fragment elaboration, fragment-based approved drugs); drug repositioning (principles and challenges, case studies); biological products; innovative chemical modalities for challenging targets: undruggable targets and multispecific drugs (sequentially obligate multispecific drugs, matchmakers, PROTAC). Hit triage and prioritization: physicochemical and substructure filters; PAINS.
- Hit-to-lead development: challenges and objectives; multiparameter optimization; structure-activity relationship; bioisosterism and non-classical isosteres; SAR studies, structure modification strategies and application rules for hit expansion.
- Lead optimization: progression criteria and drug candidate parameters; lead optimization screening plan; main strategies to increase drug-likeness; case studies.

Testi adottati

The modern drug discovery process

Prerequisiti

For a better understanding of the theoretical knowledge and technical skills, the student must have learned: - General chemistry and organic chemistry - Physics - Biology of cell - Biochemistry

Modalità di valutazione

The knowledge of the students is tested through written examinations.