11777 - Medicinal and Toxicological Chemistry 2

Course Unit Page

Academic Year 2018/2019

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 structures of drugs interacting with enzymes and receptors and 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

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. Stereochemistry and synthesis of selected drugs.

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.

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 registration on AlmaEsami is required.

Office hours

See the website of Anna Minarini