91039 - Medicinal and Toxicological Chemistry II

Learning outcomes

By the end of the course, the student should gain a good understanding of the structural and mechanistic aspects of the drug-target interaction, with particular focus on the main classes of drugs interacting with the receptors of autonomic nervous system neurotransmitters, the intracellular receptors, the enzymes and the ion channels. In particular, the student acquires the basic skills to understand the chemical synthesis, the structure-activity relationships, the mechanism of action and the chemical-toxicological aspects of the drug classes dealt during the course.

Course contents

GENERAL PART

Concept of receptor. Types and nature of receptors. The bonds of the drug-receptor complex. Receptor activation: receptor theories. Competitive and non-competitive antagonism. Reverse agonism. Classification, location, function, structure, active site, second messenger and events following activation of adrenergic, cholinergic, histaminergic receptors.

DESCRIPTIVE PART

Cholinergic system: Acetylcholine, biosynthesis, metabolism, structure-activity relationships (SAR). Cholinergic receptor subtypes.

Muscarinic agonists, muscarinic SAR.

Muscarinic antagonists: SAR atropine and analogues, synthetic derivatives. Therapeutic use, general ester synthesis. Selective antagonists for receptor subtypes: SAR, pyrenzepine synthesis, metoctramine.

Nicotinic agonists: SAR nicotine and analogues

Nicotinic antagonists. Ganglioplegics, examples, SAR, pempidine synthesis. Curars, examples, SAR, succinylcholine synthesis, pancuronium.

Anticolinesterases: Mechanism of acetylcholine hydrolysis. SAR carbamates and reversible inhibitors (physostigmine, tacrine, donepezil) examples, carbamate synthesis: neostigmine/edrophonium, tacrine synthesis, SAR irreversible inhibitors (organophosphorus).

Adrenergic system: Biosynthesis and metabolism of catecholamines. Adrenergic receptor subtypes. Adrenalin and noradrenalin SARs.

Alpha-adrenergic agonists. Phenylethylamines, imidazolines, SAR, examples. Nasal decongestants, Anorectics, Amphetamine and Ephedrine. SAR, synthesis of catecholic and related derivatives (adrenalin, ethylephrine), Clonidine synthesis.

Alpha-adrenergic antagonists. Indole alkaloids, ergot alkaloids, imidazoline derivatives, quinazoline derivatives (prazosin synthesis), benzodioxane derivatives, aloalkylamines, disulphide tetrammines: SAR

Beta-adrenergic agonists. Development, SAR, resoprenaline/terbutaline synthesis, salbutamol.

Beta-adrenergic antagonists. Development, SAR arylethanolamines and aryloxy propanolamines, stereochemical aspects, example structures.

MAO inhibitors (classification, structure, iproniazide synthesis). Tricyclic antidepressants type 6,7,6 (structure, mechanism of action). Selective biogenic amine inhibitors.
 
Histamine and Antihistamines: Biosynthesis, metabolism and structural aspects histamine, SAR, histaminergic receptor subtypes, agonists.

H1 Antihistamines: Ethylenediamines derivatives, SAR, tripelenamine synthesis; Ethanolamine derivatives, SAR, diphenhydramine synthesis; Propylamine derivatives, SAR chlorphenamine synthesis.

Histamine release inhibitors: Sodium chromoglycate, SAR, therapeutic use

H2 antihistamines, imidazole derivatives: SAR, cimetidine synthesis; dimethylaminofuran derivatives: SAR, ranitidine synthesis; guanidinothiazole derivatives, piperidinomethylphenoxy derivatives: SAR Diaryl compounds: SAR.

Non-histamine antisecretors: omeprazole, SAR and mechanism of gastric acid pump inhibition.

GABA system. Benzodiazepines (structure, mechanism of action, therapeutic use, metabolism, SAR). Anxiolytics with non-benzodiazepine structure. Antagonists. Other drugs acting on the gabaergic system.

Dopaminergic agonists (antiparkinson's): Role of dopamine and acetylcholine. Dopaminergic agonists, Dopa-decarboxylase inhibitors, MAO-B inhibitors, COMT inhibitors.

Dopaminergic antagonists (Neuroleptics): Phenothiazines (Structure, mechanism of action, SAR, related compounds). Butyrophenones. Benzamides. Reserpine and analogues. Atypical antipsychotics.

Opioid analgesics: morphine, oripavin derivatives, morphinanes, benzomorphanes, 4-phenylpiperidines and diphenylpropylamines (Mechanism of action, therapeutic use, SAR); partial agonists and antagonists.

Serotonin and the serotonergic system.

Readings/Bibliography

Foye's Principles of Medicinal Chemistry (English Edition)

Teaching methods

The course is taught in English and involves frontal theoretical activities. All examination topics will be covered

Assessment methods

The examination consists of an oral interview aimed at assessing whether the student has achieved the learning outcomes and acquired the knowledge expected from the course.

During the examination, students will also be required to write the chemical synthesis of two drugs selected from those covered during the course and explicitly indicated in the syllabus. This will be followed by two broader questions on general topics. The assessment will focus on the accuracy of the answers provided, with particular emphasis on the relationships between chemical structure, biological activity, and drug–target interactions.

Students are therefore expected to possess the knowledge acquired in previous courses, particularly Organic Chemistryand Biochemistry.

To be admitted to the examination, students must have attended at least 80% of the laboratory sessions and 70% of the lectures. Students are also reminded to check the prerequisite requirements specified in the degree programme.

Students with specific learning disorders (SLD) or temporary or permanent disabilities are encouraged to contact the University's dedicated support service as early as possible (https://site.unibo.it/studenti-con-disabilita-e-dsa/en/for-students ) in order to discuss appropriate examination accommodations. Requests for accommodations must be submitted to the course instructor at least 15 days before the examination date. The instructor will evaluate the proposed accommodations in light of the course learning outcomes.

Use of Artificial Intelligence (AI). The use of Artificial Intelligence tools during the examination is not permitted. Any unauthorized use of AI constitutes a violation of the University's principles of academic integrity.

Teaching tools

Video projector - PC system. The slides presented in class are made available to students at the University of Bologna via the IOL platform

Office hours

See the website of Andrea Milelli