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."

In view of this, the first part of the course (general part) 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 drugs able to counteract inflammatory processes. 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 and healthcare sectors

The course will address the following topics: 1. Historical overview and general aspects about drug discovery and medicinal chemistry development. 2. Main molecular targets 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. 3. Forces involved in drug-receptor interactions: London dispersion force and Van der Waals interactions, hydrophobic interaction, hydrogen bond, charge transfer complex, dipoles and ionic interactions, covalent bonds. Stereoisomers and stereospecific interactions. Conformational isomers, rigid analogs and study of the bioactive conformation. Pharmacophore identification. 4. Physico-chemical properties of drugs: substituent effects (electronic, lipophilic and steric) and measurement methods; Q.S.A.R. hints and equations of Ferguson and Hansch; acid-base properties and  Henderson-Hasselbach equation; lipophilicity/hydrophilicity: partition coefficient and distribution coefficient; solvent properties of water, solubility, solubility prediction and rate of dissolution (Noyes-Whitney equation); stereochemistry and specific rotation; molecular hindrance. 5. Physico-chemical properties, pharmaceutical formulation and administration routes. Physico-chemical properties and pharmacokinetic beahavior: gastro-intestinal tract, mechanism of drug absorption and absorption rate (Fick equation and Michaelis-Menten eaquation); capillary permeability in different districts of the body and blood brain barrier; prediction of drug absorption: Lipinski rule, PSA (polar surface area) and "flexibility"; main pharmacokinetic parameters and their determination (AUC, bioavailability, Cmax, Tmax, Css, apparent volume of distribution, clearance, % binding to plasma proteins, T1/2 and duration of drug action). 6. Phase I and phase II methabolic reactions (oxidations, reductions, hydrolysis, conjugations); drugs toxicity. 7. Discovery and structural modification of new drug-candidate: lead compound and lead optimization through functional groups modification. Isosteres, biososteres and prodrugs. 8. Classification of drugs. 9. Drugs affecting cholinergic neurotransmission (muscarinic agonists, antimuscarinic agents, acethylcholinesterase inhibitors, nicotinic antagonists). 10. Local anesthetics. 11. Central analgesics (opioids). 12. Antipyretics and non steroidal anti-inflammatory drugs (paracetamol, COX1/COX2 inhibitors, antigout agents). 13. Corticosteroids. 14. Histamine antagonists and related antiallergic drugs. 15. Drugs affecting dopaminergic neurotransmission (antipsychotics and antiparkinsons). 16. Drugs affecting serotoninergic and adrenergic neurotransmission (antidepressant). 17. Drugs affecting GABAergic neurotransmission (sedatives-hypnotics, anxiolytics, antiseizures, central myorelaxants).

Organic Chemistry (mandatory, as from school regulations).

Please Note: Medicinal Chemistry, by definition,  is concerned with the study of  the relationships between chemical structure and biological activity of pharmacologically active compounds (see IUPAC definition). Therefore, to address the content of the course and understand its technical language,  it is very important to have acquired the knowledge gained from the study of the General Physiology and related subjects, such as Anatomy and Biochemistry, as well as the knowledge derived from the study of Organic and Inorganic Chemistry.

D1 (knowledge and understanding): 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.

D2 (applying knowledge and understanding): 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.

D3 (making judgements): the student will have to indicate the most appropriate molecule for therapeutic treatment of a disease, based on knowledge of the relationships between its physico-chemical characteristics, and the pharmacokinetic and pharmacodynamic behavior.

D4 (communication skills): 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.

D5 (learning skills): 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

Attendance is recommended, but not mandatory

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)

Foye - Lemke - Zito - Roche - Williams: "Essentials of Foye's Principles of Medicinal Chemistry" (In comparison with the integral version, indicated above, It contains updated informations, and summarizes the most important chemical elements of therapeutically relevant drug classes. See chapters: 2,3, 5,7, 8, 9, 12, 18, 21, 22)

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

As long as it is necessary to carry out the exams remotely, the oral modality will be used. However, students will be required to write molecular structures, metabolic reactions, reaction mechanisms of some drugs, discussing SAR through pharmacophoric structures, and answering questions, according to the typical scheme of a written exam (examples can be found within the moodle platform. Other questions with which to practice are within the lesson slides)

When it will be restored to everyone the possibility of carrying out face-to-face examinations, the procedures will be as follows:

candidates must pass a written test to access oral examination (18-22 open questions, 2h; depending on the degree of learning globally expressed, the following judgments will be attributed to the written test: insufficient, sufficient, fair, good, excellent). The examination can be carried out only one time for each two-dates session (as in September), and two times for each three-  or four-dates session (for example, the summer session which includes the extra examination date of April). Assessment objectives: 1) the written test with open questions aims to accurately verify the knowledge of the students on a large variety of topics, and to evaluate their reasoning ability according to the specific logic and language of the discipline; 2) the oral examination aims to complete the assessment of the knowledge acquired, to evaluate the oral communication skills, and to better investigate unsatisfactory answers in the written test.

Disability and Specific Learning Disorders (SLD)

Students who have registered their disability certification or SLD certification with the Inclusion and Right to Study Office can request to use conceptual maps (for keywords) during exams.

To this end, it is necessary to send the maps, two weeks before the exam date, to the course instructor, who will verify their compliance with the university guidelines and may request modifications.

Teaching

same as for attending students

Course books

same as for attending students

Assessment

same as for attending students

Disability and Specific Learning Disorders (SLD)

Students who have registered their disability certification or SLD certification with the Inclusion and Right to Study Office can request to use conceptual maps (for keywords) during exams.

To this end, it is necessary to send the maps, two weeks before the exam date, to the course instructor, who will verify their compliance with the university guidelines and may request modifications.