DESIGN OF NEW DRUGS
Academic year and teacher
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- Versione italiana
- Academic year
- 2022/2023
- Teacher
- RICCARDO RONDANIN
- Credits
- 6
- Didactic period
- Secondo Semestre
- SSD
- CHIM/08
Training objectives
- The main purpose of the course is the learning of the basic concepts that are used in drug design. At the end, students should clearly understand the key role of lead compounds, with the strategies focused on their identification and subsequent activity optimization in order to obtain drug candidates. Important concepts achieved by students will be isostery, bioisostery, chemical modulations through structural simplification or complication, pharmacophore identification, QSAR and basic concepts used in computational chemistry, and prodrugs design. At the same time, students will get basic information about patents and other financial protections obtainable for new drugs.
Prerequisites
- To have passed the exams of Organic Chemistry I and II
To have passed the exam of Medicinal and Toxicological Chemistry I Course programme
- Planning a new drug research: choice of the disease and the target. The bases of pharmaceutical patent. The orphan drugs. Classical methods of drug design. Methods for the search and the development of “Hit” and “Lead” compounds. Combinatorial synthetic methods. Fragment Libraries. Chemical strategies aimed at optimization of the Lead pharmacokinetic and pharmacodynamic features: improvement of interaction and selectivity with the target, structural modulation influencing lipophilic, electronic and steric properties. Isosteric and bioisosteric structural modifications. Molecular simplification and complication. Stereochemical issues. Projecting focused prodrugs. Quantitative structure- activity relationships (QSAR). Bases of molecular modelling. Quantum mechanics vs molecular mechanic methods. Concepts of 3D pharmacophore, ComFA, the Protein Data Bank, virtual screening, docking and scoring. Molecular Dynamic basic concepts. Some examples of drug discovery: EGFR inhibitors. Modern approaches in drug discovery: the Proteolysis-Targeting Chimera (PROTAC) system. Basic concepts in retrosynthetic analysis.
Didactic methods
- Class lectures for all the course arguments. Together with theorical arguments, practical examples from literature are reported and the students are requested to suggest alternative proposals and criticisms to the presented method.
Learning assessment procedures
- The examination test is oral. The student should demonstrate to know the basic approaches used for the drug discovery and optimization via classic and modern methods as discussed in the class lessons. The test also comprises exercises in which, from a possible lead structure, a series of analogues with improved characteristics should be proposed, following a rational design through isosteric substitutions, structure simplifications or complications, prodrugs design, together with a plausible chemical feasibility.
Reference texts
- 1) G. L. Patrick, Chimica Farmaceutica, III edizione, EdiSES 2015
2) E. Stevens, Chimica Farmaceutica. I processi di scoperta dei farmaci, Piccin, 2015.
3) A. Gasco, F. Gualtieri, C. Melchiorre, Chimica Farmaceutica, Casa Editrice Ambrosiana, 2020.
4) R. B. Silverman, M. W. Holladay, Manuale di Chimica Farmaceutica. Progettazione, Meccanismo d’Azione e Metabolismo dei Farmaci, Edra, 2015.
