MEDICINAL CHEMISTRY

Tracey Pirali (9 h – 1.5 ECTS)

Tracey Pirali obtained her degree in Chemistry and Pharmaceutical Sciences in 2004. She then had research experiences in CNRS (Paris, visiting scientist) and Edinburgh (visiting professor). At present she is an Associate Professor in Medicinal Chemistry. She has authored about 30 papers in international journals. Recently, her work was covered by C&EN. She is a named inventor on three patents in the field. She recently co-founded a Spin-off company concentrating on calcium channel modulators. In 2012 she was awarded the Farmindustria Prize by the Italian Chemical Society.

At present she organizes an optional course for Chemistry and Pharmaceutical Sciences last-year students on design and synthesis on novel bioactive compounds and is on the review board of the Pharmaceutical Chemistry and Technology degree.

Academic lecturers: 9

Guest lecturers: 0

Laboratory: 0

Gian Cesare Tron (9 h –1.5 ECTS)

He received his PhD in Organic Chemistry in 2001 at the Università di Torino (Italy) and, at present, he is an Associate Professor of Medicinal Chemistry at UPO. He spent sabbatical leaves in the laboratory of Prof. Jieping Zhu (Institut de Chimie des Substances Naturelles – Gif-surYvette, France), Varinder K. Aggarwal (School of Chemistry – Bristol, UK) and Valery Fokin (The Scripps Institute – La Yolla, USA). In 2007 he was awarded the Farmindustria Prize for his achievements in medicinal chemistry. His research interests concern the discovery of new multicomponent reactions and their application in the field of medicinal chemistry.

Academic lecturers: 9

Guest lecturers: 0

Laboratory: 0

Title	Medicinal chemistry (3 ECTS)
Program	Absorption. Mechanisms of absorption with a focus on skin. Phase I and phase II metabolism with a focus on skin metabolism. Drug-target intermolecular interactions and SAR studies. Role of stereochemistry in the interaction with the binding site. Receptors and enzymes as drug targets. Evaluation of the drug potency. Enzymatic inhibitors. Competitive reversible, non-competitive reversible, irreversible inhibitors, transition-state analogues, suicide substrates. Drug discovery. Hit compounds and lead compounds. Finding a hit: natural products, serendipity, natural ligand modifications, me-too drugs, SOSA approach, high-throughput screening, repositioning drugs. How to recognize drug-like molecules. LogP and logD. Lipinski rules and beyond. Strategies for lead optimization. Prodrugs and soft drugs. Isosteres and bioisosteres, classic and non-classic bioisosteres. Case studies of successful drug discovery. A seminar by a guest lecturer from the industrial world on the discovery and development of drugs from a MedChem point of view
Textbooks	G.L. Patrick, An introduction to medicinal chemistry, EdiSES; E. Stevens, Medicinal Chemistry: The Modern Drug Discovery Process, Pearson.
Objectives	The aim is to introduce the student to the main principles of medicinal chemistry. 1. At the end of the course the student will know and understand the basic concepts of medicinal chemistry, in particular the route followed by the drug in the organism, from its administration to its excretion. Moreover, the itinerary of the drug in the pharmaceutical industry, from drug discovery to drug development through drug design, will be addressed. 2. The student will apply the acquired knowledge and understanding in the recognition of the chemical structures, in the discussion of the chemical and chemical-physical properties, of the mechanism of action, of the structure-activity relationship and of the metabolic fate. 3. The student will acquire the ability to analyse texts and papers in the medicinal chemistry literature. 4. The student will learn to communicate about his/her understanding, to describe, even in an original way, a topic described during lessons, to adequately answer to questions, critiques and suggestions. 5. The student will have the learning skills to handle in a dynamic way his/her knowledge in medicinal chemistry with a good degree of autonomy.
Prerequisites	Basic knowledge of biology, biochemistry, pharmacology and physiology.
Teaching methods	Lectures and case studies.
Expected Results	At the end of the course, the student will know the basic principles of medicinal chemistry. He/she will be able to apply these principles to a specific bioactive molecule and to evaluate its chemical, metabolic and drug-likeness properties. The student will also know the role of medicinal chemistry in drug discovery and in drug design and the strategies that can be used in order to improve the pharmacodynamic and pharmacokinetic properties of a bioactive molecule.
Exam modality	Written test (max. score 25). It covers the material delivered in lectures. Multiple choice, true/false and completion type questions are the most frequent types of questions. 1 point for the correct answer, 0 points for wrong or blank answers. Essay on a dermatological FDA approved small molecule (max. score 7). It should cover the main medchem aspects (metabolism, synthesis, intermolecular interactions, discovery and optimization, stereochemistry, LogP, LogD, etc.). The essay is individual and the drug is assigned by the lecturers. Rules – max 4 pages, single line spacing, font size 12 + schemes and figures + bibliography. Turnitin check.

TITLE

Medicinal chemistry (3 ECTS)

PROGRAM

Absorption. Mechanisms of absorption with a focus on skin.

Phase I and phase II metabolism with a focus on skin metabolism.

Drug-target intermolecular interactions and SAR studies.

Role of stereochemistry in the interaction with the binding site.

Receptors and enzymes as drug targets.

Evaluation of the drug potency.

Enzymatic inhibitors. Competitive reversible, non-competitive reversible, irreversible inhibitors, transition-state analogues, suicide substrates.

Drug discovery. Hit compounds and lead compounds. Finding a hit: natural products, serendipity, natural ligand modifications, me-too drugs, SOSA approach, high-throughput screening, repositioning drugs.

How to recognize drug-like molecules. LogP and logD. Lipinski rules and beyond.

Strategies for lead optimization.

Prodrugs and soft drugs.

Isosteres and bioisosteres, classic and non-classic bioisosteres.

Case studies of successful drug discovery.

A seminar by a guest lecturer from the industrial world on the discovery and development of drugs from a MedChem point of view

TEXTBOOKS

G.L. Patrick, An introduction to medicinal chemistry, EdiSES;

E. Stevens, Medicinal Chemistry: The Modern Drug Discovery Process, Pearson.

OBJECTIVES

The aim is to introduce the student to the main principles of medicinal chemistry. 1. At the end of the course the student will know and understand the basic concepts of medicinal chemistry, in particular the route followed by the drug in the organism, from its administration to its excretion. Moreover, the itinerary of the drug in the pharmaceutical industry, from drug discovery to drug development through drug design, will be addressed. 2. The student will apply the acquired knowledge and understanding in the recognition of the chemical structures, in the discussion of the chemical and chemical-physical properties, of the mechanism of action, of the structure-activity relationship and of the metabolic fate. 3. The student will acquire the ability to analyse texts and papers in the medicinal chemistry literature. 4. The student will learn to communicate about his/her understanding, to describe, even in an original way, a topic described during lessons, to adequately answer to questions, critiques and suggestions. 5. The student will have the learning skills to handle in a dynamic way his/her knowledge in medicinal chemistry with a good degree of autonomy.

PREREQUISITES

Basic knowledge of biology, biochemistry, pharmacology and physiology.

TEACHING METHODS

Lectures and case studies.

EXPECTED RESULTS

At the end of the course, the student will know the basic principles of medicinal chemistry. He/she will be able to apply these principles to a specific bioactive molecule and to evaluate its chemical, metabolic and drug-likeness properties. The student will also know the role of medicinal chemistry in drug discovery and in drug design and the strategies that can be used in order to improve the pharmacodynamic and pharmacokinetic properties of a bioactive molecule.

EXAM MODALITY

Written test (max. score 25). It covers the material delivered in lectures. Multiple choice, true/false and completion type questions are the most frequent types of questions. 1 point for the correct answer, 0 points for wrong or blank answers.

Essay on a dermatological FDA approved small molecule (max. score 7). It should cover the main medchem aspects (metabolism, synthesis, intermolecular interactions, discovery and optimization, stereochemistry, LogP, LogD, etc.). The essay is individual and the drug is assigned by the lecturers.

Rules – max 4 pages, single line spacing, font size 12 + schemes and figures + bibliography. Turnitin check.

Last modified: July 13, 2020

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