Medicinal chemistry

Goals
An introduction to Medicinal Chemistry. The course aims to provide students with the general principles and the basic approaches of Medicinal Chemistry. In particular, the principal phases of drug action, the molecular mechanisms of drugs and the drug discovery and development process will be discussed.

Course content
Principal phases of drug action (20 hours). Pharmaceutic, pharmacokinetic and pharmacodynamic phases. Pharmacokinetics: the processes of Absorption, Distribution, Metabolism, and Excretion of drugs. Pharmacodynamics: the molecular targets of drugs and the receptor concept. Structure and function of the receptors. Nature of drug-receptor interactions. Quantitative analysis of drug-receptor interactions and drug-induced biological responses (cell-free binding assays and cell-based functional assays). Definition of affinity, potency, efficacy, selectivity, therapeutic index. Definition of agonist, partial agonist, inverse agonist, antagonist. Receptor theory: models for drug-mediated receptor activation. Processes of signal transduction. Enzymes as drug targets.
Principal phases of drug discovery and development process (14 hours). Approaches for HIT and LEAD identification. LEAD modification and optimization: isostery and bioisostery; molecular simplification and complication; chemical and physico-chemical modulation, rigid analogs and chiral modulation. Molecular modification of peptides. Recent advances in the design of peptidomimetics. Introduction to structure-activity relationship studies (QSAR) and computer-aided drug design methods (CADD). Computer lab lesson on the use of structural databases and virtual screening tools.
Analysis of selected pharmacological classes to illustrate the points discussed in the general section (14 hours).

Reference material
- G. L. Patrick, An introduction to Medicinal Chemistry, Fifth edition, Oxford University Press
- T. L. Lemke, D. A. Williams, V. F. Roche, S. W. Zito, Foye's Principles of Medicinal Chemistry, Seventh edition, Lippincott Williams & Wilkins, Wolters Kluwer

Prerequisites
Basic knowledge of organic chemistry.

Assessment method: Written
The exam will consist of a written test which aims to verify the preparation of the student on the course contents. The written examination will typically include 4-5 open questions: 1-2 questions will concern the phases of drug action, 1-2 questions will regard the drug discovery and development process, 1-2 questions will refer to drug classes discussed during the course.

Language of instruction
English

Attendance Policy: Strongly recommended

Mode of teaching: Traditional

Website:
http://lbelvisimc.ariel.ctu.unimi.it/v1/home