The aim of this course is to provide students with the basic knowledge of the chemical-physical properties that affect the activities of the drugs, as well as the the strategies used for their design and optimization. The course also aims to provide the basis for understanding chemical properties, metabolic stability and synthetic approaches of selected classes of drugs.

The first part of the course will be devoted to present the fundamentals of medicinal chemistry emphasizing the key connections between the molecular structure of drugs, their physico-chemical properties and their biological activity.The second part of the course will be devoted to the systematic description of representative classes of drugs acting on the nervous system. In this context, particular emphasis will be given to the description of drug design, structure activity relationships and synthetic strategies.

General Part
Definition and objectives of medicinal chemistry. Overview of drug discovery process and approaches. Nomenclature and drug classifications.
Physicochemical principles of drug action: solvent properties of water; solubility; partition coefficient; acid-base properties.
Drug-molecular target interaction: forces involved (Dispersion or van der Waals forces, Hydrophobic interactions, Hydrogen bonding, Charge transfer, Dipoles, Ionic bonds, Covalent bonds, halogen bond).
Stereochemical aspects of drug action: optical, geometrical and conformational isomerism;constrained analogs; approaches to obtain enantiomerically pure medicinal drugs (asymmetric synthesis, resolution of racemates, derivatization of chiral compounds)
Physicochemical properties influencing pharmacokinetics: passage of drugs through membranes; biotransformation reactions (phase I and phase II).
Pharmacodynamics: structurally specific and non-specific drugs
- Drug-receptor interactions: agonists, antagonists, inverse agonists, allosteric modulators. Dose-response curves
Molecular targets of drugs: structure and function of ion channel receptors, G-protein-coupled receptors and nuclear receptors

Quantitative structure-activity relationships: Ferguson's rule, Hammett correlations, the Hansch linear free-energy model, the Free-Wilson method, 3D-QSAR studies using the CoMFA protocol.
Isosterism, bioisosterism
prodrugs
Drug design: basic approaches

Descriptive Part
Structure, nomenclature, physicochemical properties, structure-activity relationships, molecular mechanism of drug action, and biotransformation reaction of prototypes of selected drug classes acting on neurotransmitters and their receptors:
Drugs affecting cholinergic neurotransmission (Acetylcholine - structure, biosynthesis, conformational studies, SARs, and receptor binding. Structure of the nicotinic and muscarinic receptor. Design of acethylcholine analogues. Cholinergic agonists. Muscarinic antagonists. Nicotinic antagonists. Acethylcholinesterase and anticholinesterase drugs. Antidotes for irreversible acethylcholinesterase inhibitors).
Drugs acting on dopaminergic receptors (dopamine: Biosynthesis, catabolism, conformational studies and receptors, L-DOPA, Dopamine agonists and antagonists, dopamine reuptake inhibitors)
Drugs affecting serotonergic and/or adrenergic neurotransmission (antidepressants: serotonin and/or norepinephrine reuptake inhibitors)
Drugs acting on histamine receptors (Structure, conformation and protrotropic equilibria of histamine. The histamine receptors. H-1 histamine agonists and antagonists).
Opioid analgesics (Opium alkaloids. Morphine: structure, properties, and SARs. Development of morphine analogues: variation of substituents; drug extension; simplification or drug dissection; rigidification. Opioid receptors. Endogenous opioid peptides. Opiate agonists, antagonists and mixed agonist-antagonists).
Drugs acting on the GABAergic neuronal system (Gamma-Aminobutyric acid: biosynthesis and metabolism. GABAergic receptors. GABA agonists and antagonists; GABA inhibitors. Barbiturates, benzodiazepines).

The course also include an overview of the structure activity relationships and mode of action of the following classes of drugs: Nonsteroidal Anti-inflammatory Agents; Local anesthetics; Volatile anesthetics; MAO inhibithors; COMT inhibitors

Selected examples of drug synthesis and drug development are also discussed

Passing Organic Chemistry I

At the end of the course, the student is expected to acquire knowledge and understanding of the basic principles relating the molecular structure of representative drugs to their biological properties and reactivity.
Another goal of the course is to acquire the ability to apply knowledge and understanding of principles underlying metabolic and organic drug transformations to predict the outcome of metabolic chemical transformations, and to propose solutions for the synthesis and optimization of small molecules of pharmaceutical interest. The student should also be able to apply the acquired knowledge about the mechanism of drug action for the management of human pathologies

The student should be able to combine the topics covered in class and interdisciplinary topics taught in other courses , to develop the ability to propose solutions to medicinal chemistry problems
The course aims at the achievement of communication skills, by employing appropriate language, to transfer clearly the acquired drug information to other people
Finally, the student should acquire the ability to update drug information and drug design strategies through continuous use of textbooks, scientific papers and specific database.

The teaching material prepared by the lecturer in addition to recommended textbooks (such as for instance slides, lecture notes, exercises, bibliography) and communications from the lecturer specific to the course can be found inside the Moodle platform › blended.uniurb.it

Teaching

Frontal oral lessonsFrontal oral lessons
Exercises dealing with the design, synthesis, and metabolic transformation of simple molecules will be proposed allowing the student to check applying knowledge, understanding and learning skills, in line with the above mentioned objectives

Attendance

Basic knowledge of organic chemistry, anatomy, physiology and biochemistry
In general, regular attendance at lessons facilitates the acquisition of the skills needed to pass the exam

Course books

Recommended book: A. Gasco,  F. Gualtieri, C. Melchiorre - Chimica Farmaceutica - Ambrosiana (Rezzano, Mi): Chapters 1-15, 27, 30.

Assessment

The final exam consists of an oral colloquium, lasting about 40-45 minutes, aimed at assessing the level of knowledge and understanding achieved by students on the theoretical contents listed in the program. Questions are asked about the general principles of medicinal chemistry, and about the properties of specific pharmaceutical classes. About the drugs included in the program, the student must know the structure, the name, the mechanism of action at the molecular level (if known), the structure-activity relationships, and the putative metabolic transformations; he must be also able to discuss a synthetic approach for the synthesis of representative drugs. We will also evaluate the presentation skills and the student's ability to interconnect the various topics covered during the course and in an interdisciplinary manner, as well as the ability to deal and solve medicinal chemistry problems inherent in the issues carried out.

Disabilità e DSA

Le studentesse e gli studenti che hanno registrato la certificazione di disabilità o la certificazione di DSA presso l'Ufficio Inclusione e diritto allo studio, possono chiedere di utilizzare le mappe concettuali (per parole chiave) durante la prova di esame.

A tal fine, è necessario inviare le mappe, due settimane prima dell’appello di esame, alla o al docente del corso, che ne verificherà la coerenza con le indicazioni delle linee guida di ateneo e potrà chiederne la modifica.