03427 - Medicinal Chemistry II

Learning outcomes

The course deals with the fundamental strategies of design and synthesis of drugs and with the molecular mechanism of drug action. the chemical structuresof drugs interacting with enzymes and receptorsand their structure-activity relationship.Particularly the student will be learn the principal classes of agents acting on central and peripheral nervous systems.

Course contents

Neurotransmitter receptors

The bonding of ligands to receptors. Structure and classification of receptors. General mode of operation. Ligand-response relationships: agonist and antagonist concentration-response relationships, partial agonism, inverse agonism. Ligand-receptor theories: Clark's occupancy theory, the rate theory, two-state model, perturbation theory. Classification, localization, function, structure, active site of adrenergic receptors, cholinergic receptors, dopaminergic receptors, GABAergic receptors, and opioid receptors.

Neurotransmitters

Acetylcholine, catecholamines, serotonin, histamine, 4-aminobutyric acid, enkephalins: biosynthesis, release, uptake, metabolism, molecular properties, active conformation, stereochemical properties.

Drugs acting at neurotransmitter receptors and enzymes

Structure-activity relationships, mechanism and site of action, therapeutic use, side effects, stereochemistry, and synthetic aspects of drugs acting at adrenergic, dopaminergic, cholinergic, serotoninergic, histaminergic, GABAergic, and opioid systems. Acetylcholine esterase inhibitors. Angiotensin–Converting Enzyme Inhibitors. Stereochemistry and synthesis of selected drugs:succinylcholine, atracurium, pancuronium, atropine, trihexyphenidyl, tropicamide, dicycloverine, donepezil, physostigmine, adrenaline, ethylephrine, ephedrine, clonidine, prazosin, salbutamol, reproterol, general synthesis of aryloxypropanolamines, practolol, diphenhydramine, promethazine, ranitidine, disodium cromoglycate, omeprazole, chlorpromazine, fluphenazine, clozapine, chlordiazepoxide, triazolam, oxazepam, diazepam, fentanyl, etorfine and fluoxetine.

Drug design

Basic principles of rational drug design. Drug design strategies. Modification of a lead compound.

Readings/Bibliography

Chimica Farmaceutica, a cura di A.Gasco, F. Gualtieri, C. Melchiorre- Casa Editrice Ambrosiana, 2014

T. L. Lemke, D. A. Williams et al. - Foye's Principi di Chimica Farmaceutica - Piccin, Padova, 2014

C. Melchiorre - I recettori dei neurotrasmettitori: un'introduzione per la chimica farmaceutica - CLUEB, Bologna, 1996.

C. Melchiorre, A. Minarini, M. Recanatini, V. Tumiatti, M.L. Bolognesi - I recettori colinergici - CLUEB, Bologna, 1997.

F. Gualtieri, M.N. Romanelli, E. Teodori - Chimica farmaceutica dei recettori: disegno e sintesi di farmaci e mezzi di indagine farmacologica - CLUEB, Bologna, 1997.

M. Giannella, W. Quaglia - I recettori adrenergici - CLUEB, Bologna, 1998.

G. Ronsisvalle, M. Pappalardo, L. Pasquinucci, O. Prezzavento – I recettori oppioidi – CLUEB, Bologna, 1999.

D. Lednicer, L. A. Mitscher - The organic chemistry of drug synthesis, Voll. 1-6 - John Wiley & Sons, New York, 1977, 1980, 1984, 1990, 1995, 1999.

Teaching methods

The course includes theoretical lessons and attendance is mandatory. The theoretical lessons are designed to convey to the student the knowledge of the main synthetic strategies for drug preparation, the mechanisms of action of agonists and antagonists that act on the different receptor systems and the structure-activity relationships of drugs.

Assessment methods

As a preliminary test, the student should describe the synthesis of two drugs among those in the program. If this test is passed, the examination continues with a discussion on three topics of the course drawn from the student. The student can also choose to take the oral interview in the immediately following session, as long as it is within the same exam session. Two appeals will be guaranteed in February, one appeal in June, one in July and two appeals in September. In the event that, after having passed the test relating to the synthesis, the oral test is not passed in the following session or the student does not appear for the session, the exam must be re-sit entirely. The registration on AlmaEsami is required.

Teaching tools

Lessons will be held by using slides.

Links to further information

https://www.unibo.it/sitoweb/anna.minarini/

Office hours

See the website of Anna Minarini