"As defined by IUPAC (International Union of Pure and Applied Chemistry), Medicinal Chemistry is a chemistry-based discipline, also involving aspects of biological, medical and pharmaceutical sciences. It is concerned with the invention, discovery, design, identification and preparation of biologically active compounds, the study of their metabolism, the interpretation of their mode of action at the molecular level and the construction of structure-activity relationships (S.A.R.), the relationships between chemical structure and pharmacological activity for a series of compounds." (from "Foye's Principles of Medicinal Chemistry", prefation).

In view of this, the first part of the course (general) aims to provide students with some theoretical concepts of medicinal chemistry, necessary to uderstand the action of drugs. Hints will also be given to the main approaches in the study of the relationships between chemical structure and biological activity.

To this end, the folloowing subjects will be discussed:

- physico-chemical properties of drugs (acid-base behavior, solubility, lipophilicity, electronic effect of substituents, molecular dimensions, reactivity, stereochemistry, drug-receptor interactions)

- some aspects of the methods used in the discovery and the development of new drugs (lead compound identification through random screening, rationale approaches, serendipity and optimization strategy, such as isosteric modification and prodrugs development)

- mechanisms and molecular targets (receptors, enzyme) responsible for the pharmacodynamic behaviour of a drug

- principles regulating the pharmacokinetic of a drug (absorption, distribution, metabolism, elimination and toxicity)

The second part of the course (systematic) represents a practical application of the general concepts presented in the first part and will describe the achievements of pharmaceutical research, dealing with drugs acting on the central and peripheral nervous system and on the immune system. Starting from the discovery of the lead compound, each class of drugs will be examined by means of structure activity relationschips, physico-chemical properties, pharmacodynamic and pharmacokinetic.

Overall, the course aims to confer characterizing knowledge, essential to cover professional roles in the pharmaceutical field.

The course will address the following topics in the order below:

Historical overview and general aspects about drug discovery and medicinal chemistry development.

Receptors and drugs action: ligand-gated ion channels, voltage-gated ion channels, G protein-coupled receptors, nuclear receptors (transcription factors), agonists, antagonits, inverse agonists, affinity, potency, efficacy and dose-response curves.

Enzyme inhibitors.

Forces involved in drug-receptor interactions: London dispersion force or Van der Waals interactions, hydrophobic interaction, hydrogen bond, charge transfer complex, dipoles, ionic interactions, covalent bonds.

Physico-chemical properties of drugs: solvent properties of water, solubility, partition coefficient and lipophilicity/idrophilicity, acid-base properties, electronic effect of substituent, molecular hindrance, reactivity, stereochemistry and drugs action.

Pharmaceutical formulation and administration routes.

Pharmacokinetics: gastro-intestinal tract, capillary permeability and blood brain barrier, mechanism of drug absorption and elimination, bioavailability, (apparent) volume of distribution, half-life and duration of drug action, physico-chemical properties influencing pharmacokinet behaviour.

Phase I and phase II methabolic reactions (oxidations, reductions, hydrolysis, conjugations), drugs toxicity.

Discovery and structural modification of new drug-candidate: lead compound and lead optimization through functional groups modification. Isosteres, biososteres and prodrugs.

Drugs affecting cholinergic neurotransmission (muscarinic agonists, antimuscarinic agents, acethylcholinesterase inhibitors, nicotinic antagonists).

Local anesthetics.

Central analgesics (opioids).

Antipyretics and non steroidal anty-inflammatory drugs (paracetamol, COX1/COX2 inhibitors, antigout agents).

Corticosteroids.

Histamine antagonists and related antiallergic drugs.

Drugs affecting dopaminergic neurotransmission (antipsychotics and antiparkinsons).

Drugs affecting serotoninergic and adrenergic neurotransmission (antidepressant).

Drugs affecting GABAergic neurotransmission (sedatives-hypnotics, anxiolytics, antiseizures, central myorelaxants).

Required: Organic Chemistry. Suggested: Biochemistry and Physiology.

- The student will have to show knowledge and understanding of the contents and concepts provided by the course, by answering specific questions, during the written and oral examinations.

-The student will have to be able to apply the knowledge and the logic acquired to formulate plausible hypotheses on the pharmacodynamic and pharmacokinetic behavior of specific substances.

- The student will have to show communication skills by formulating clear and comprehensible answers to the questions proposed, using, where necessary, the typical diagrams and the terminology of the mathematical, physical, chemical, biological, pharmacological and medical languages.

- The student will have to show learning skills necessary to undertake the study of subjects related to the course itself, and/or advanced ones.

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

Support to teaching activities will not be provided

Teaching

Frontal Lessons and training questions

Attendance

Knowledge of the main reaction mechanisms in organic chemistry is required: SN1 and 2; nucleophilic acyl substitution; electrophilic aromatic substitution; elimination; Michael reaction (nucleophilic addition to α,β-unsaturated carbonyl compounds), Diels-Alder reaction (electrocyclic reaction); oxidation and reduction; hemiacetal, acetal, hemiketal and ketal formation, radical reactions.

Knowledge of the chemical structures of the main bio-molecules is also required: aminoacids, peptides and proteins; sugars and glucides, glycerol, fatty acids cholesterol and lipids, purin and pirimidines, nucleosides and nucleotides, DNA and RNA, vitamins.

Course books

Study book:

W.O Foye, T.L. Lemke, D.A. Williams: "Principles of Medicinal Chemistry", Lippincot W&W (7th edition, chapters: 1, 2, 4, 5, 8-10, 14-18, 21, 29, 32, 33)

Reference books:

R. B. Silverman, M. W. Holladay: "The organic chemistry of drug design and drug action". Elsevier

G.L. Patrick: "An Introduction to Medicinal Chemistry", Oxford university press.

C.G. Wermuth: "The Practice of Medicinal Chemistry", Academic Press.
Laurence Brunton, Bruce A. Chabner, Björn C. Knollmann:"Goodman & Gilman: The Pharmacological Basis of Therapeutics", Lawrence Brunton.

Bertram G. Katzung e P. Preziosi: "Basic and Clinical Pharmacology", LANGE Basic Science.

University textbooks: General Biology, General and Organic Chemistry, Biological Chemistry, General Physiology, Pharmacology and General Pathology.

Assessment

to access oral examination, candidates must pass a written test (open questions, 2h)

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.