AIMS AND CONTENT

LEARNING OUTCOMES

Through the analysis of the “drug-discovery” process, the pharmacodynamic and pharmacokinetic aspects relevant in the design (rational and non-rational) and synthesis of new drugs will be discussed. The educational objective is to provide the student with the theoretical tools necessary to address the design and the preclinical development of new drug with a particular focus on computer-aided rational design methods, structure-activity relationships definition and modern synthetic procedures currently applied in medicinal chemistry.

AIMS AND LEARNING OUTCOMES

The aim of the course is to provide a general knowledge on the drug-discovery process with particular attention to:

i) the physicochemical properties affecting the pharmacokinetic and pharmacodynamic of “hit” and “lead” compounds

ii) the strategies for the rational design of new pharmaceutically relevant compounds

iii) the synthetic protocols for the efficient preparation of new active derivatives.

At the end of the course the student will master the theoretical knowledge to:

• describe the “drug-discovery” process;

• analyse the influence of pharmacodynamic and pharmacokinetic properties on drug’s activity;

• identify the functional groups and substructures potentially involved in the drug-receptor interaction and/or susceptible to metabolic instability;

• understand the physical principles underlying the computational methods of rational drug design and the scope of applicability of the various approaches;

• distinguish the different preparative methods used in the medicinal chemistry and critically analyse the pros and cons of the various approaches

TEACHING METHODS

In-person classes for a total of 40 hours.

Any Student with documented Specific Learning Disorders (SLD), or with any special needs, shall reach out to the Lecturer(s) and to the dedicated SLD Representative in the Department ( Prof. Luca Raiteri, Luca.Raiteri@unige.it ) before class begins, in order to liaise and arrange the specific learning methods and ensure proper achievement of the learning aims and outcomes. VERY IMPORTANT: any request for compensatory tools and adaptations in the exam MUST be done within 10 working days before the date of the exam according to the instructions that can be found at https://unige.it/disabilita-dsa/comunicazioni

The slides are available in aulweb website.

SYLLABUS/CONTENT

Drug discovery process. Definition of “Hit” compound and “Lead” compound.

Development of classical structure-activity relationships (SARs). Variation of substitution patterns of aromatic ring substituents. Vinilogy. (Bio)isosteres. Molecular simplification. Extension of cycles. Molecular constrain.

Pharmacokinetics. Drug absorption, distribution, metabolism and excretion.

Pharmacodynamics. Drug-receptor interactions. Salt bridges. Van Der Waals interactions. Hydrogen bond. Aromatic interactions. Halogen bond. London forces. Hydrophobic effect.

Computer-aided drug design (CADD). Energy calculation for a chemical system. Molecular docking. De-novo design. QSAR approaches. Pharmacophore maps. Molecular fields.

Synthetic methodologies in medicinal chemistry. Combinatorial synthesis. Combinatorial libraries. Solid phase synthesis. Mix&Split method. Parallel synthesis. Polymer-Assisted Solution-phase Synthesis.

RECOMMENDED READING/BIBLIOGRAPHY

Foye's. Principi di chimica farmaceutica. Piccin

Wilson & Gisvold. Chimica Farmaceutica. Casa Editrice Ambrosiana

Gasco, Gualtieri, Melchiorre. Chimica farmaceutica. Casa Editrice Ambrosiana

Costantino, Sbardella. Chimica farmaceutica. Edises

TEACHERS AND EXAM BOARD

LESSONS

LESSONS START

According to academic calendar available at https://corsi.unige.it/corsi/11673/studenti-orario

Class schedule

The timetable for this course is available here: Portale EasyAcademy

EXAMS

EXAM DESCRIPTION

The exam includes an oral interview (in presence, about 45 minutes long) concerning the topics covered during the lessons.

The exam will be considered passed if the student obtains a grade equal to or greater than 18/30.

ASSESSMENT METHODS

The oral exam aims to evaluate the student's preparation in terms of:

• mastery of the topics covered during the lessons;

• clarity of the presentation and use of proper scientific terminology

• ability to correlate the various topics as different aspects of a unique process (i.e., drug-discovery process).

FURTHER INFORMATION

For further information, please contact the professor