11777 - Medicinal and Toxicological Chemistry 2

Learning outcomes

The course of Medicinal and Toxicological Chemistry 2 is devoted to the study of the principal drug families which interact with neurotransmitter receptors of autonomic nervous system, with intracellular receptors and with cardiovascular system. About these drugs will be described their design, chemical synthesis and molecular mechanism of action. In addition structure-activity relationships, therapeutic use and related chemical-toxicological aspects will be examined.

Course contents

GENERAL PART
Receptor concept. Receptor classification. Chemical and physico-chemical characteristics of drug -receptor interactions.

SPECIFIC TOPICS
Cholinergic system: Acetylcholine: biosynthesis, metabolism, structure activity relationships (SAR). Cholinergic receptor subtypes.
Muscarinic agonists: examples, synthesis. SAR of muscarine..
Muscarinic antagonists: SAR of atropine and related derivatives. SAR of synthetic compounds. Mechanism and site of action, therapeutic use. Selective antagonists for receptor subtypes: examples, mechanism and site of action, therapeutic use, SAR and synthesis.
Nicotinic agonists: SAR of nicotine and related compounds.
Nicotinic antagonists. Ganglionic blocking agents: examples, mechanism and site of action, therapeutic use, SAR, synthesis. Neuromuscular blocking agents:examples, mechanism and site of action, therapeutic use, SAR, synthesis.
Cholinesterase inhibitors: mechanism of acetylcholine hydrolysis. Carbamates and reversibile cholinesterase inhibitors, examples,mechanism and site of action, therapeutic us, SAR. synthesis. Irreversible inhibitors:examples,
Adrenergic system: Catecholamines: biosynthesis, metabolism, structure activity relationships (SAR). Catecholaminergic receptor subtypes.
Alpha-adrenergic agonists: examples, mechanism and site of action, therapeutic use, SAR, synthesis.
Alpha-adrenergic receptor subtype agonists: example, mechanism and site of action, therapeutic use,SAR, synthesis.
Imidazolin receptor subtypes agonists: examples, mechanism and site of action, therapeutic use, SAR, synthesis. Appetite suppressants : mechanism and site of action, therapeutic use, SAR, synthesis.
Alpha-adrenergic receptor subtypes antagonists: examples, mechanism and site of action, therapeutic use, SAR, synthesis.
Beta-adrenergic receptor subtype agonists: discovery, development, examples, mechanism and site of action, therapeutic use, SAR, synthesis.
Beta-adrenergic receptor subtype antagonists: 1st, 2nd, 3rd generation: examples, mechanism and site of action, therapeutic use, SAR, synthesis.
Local anestetics: discovery, development. Benzoic acid and amide derivatives: mechanism and site of action, therapeutic use, SAR, synthesis. Cocaine: mechanism and site of action, SAR.
Diuretics. Classification. Mechanism and site of action, therapeutic use, SAR, synthesis of osmotic diuretics,carbonic anhydrase inhibitors, solfonamide derivatives,ethacrynic acid derivatives, aldosterone antagonists and various compounds.
Histamine and Histamine Antagonists: histamine: biosynthesis and metabolism, SAR, histamine receptors subtypes.
Histamine receptor H1 antagonists: discovery, development, examples, mechanism and site of action, therapeutic use, SAR, synthesis.
Istamine release inhibitors: examples, therapeutic use, SAR, synthesis.
Histamine receptor H2 antagonists: development, examples, mechanism and site of action, therapeutic use, SAR, synthesis.
Histamine receptor H3 agonists and antagonists: development, examples, mechanism and site of action, SAR.
Antisecretory agents: omeprazole, lansoprazole, mechanism and site of action, therapeutic use, SAR, synthesis.
Cardiovascular agents: Cardiac glycosides: structure, biosynthesis, mechanism and site of action, therapeutic use, SAR, receptor hypothesis.
Antiarrhythmic drugs: classification, examples, mechanism and site of action, therapeutic use, SAR, synthesis.
Calcium modulators: classification, mechanism and site of action, therapeutic use, SAR, synthesis. Drugs for the treatment of angina pectoris: classification, examples, mechanism and site of action, therapeutic use, SAR, synthesis.
Antihypertensive drugs: classification, direct vasodilators: examples, therapeutic use, SAR.
RAS inhibitors: examples, mechanism and site of action, therapeutic use, SAR, synthesis.
Angiotensin II receptor blockers: development, examples, therapeutic use, SAR, synthesis.
Steroid hormones: biosynthesis, steroid receptors. Estrogens: natural occurring and synthetic estrogens: examples, mechanism and site of action, therapeutic use, SAR, synthesis.
Estrogen receptor modulators: receptor antagonists, triphenylethylamine derivatives, tamoxifen, raloxifene and related compounds, mechanism and site of action, therapeutic use, SAR, synthesis. Aromatase inhibitors: steroidal e non steroidal derivatives, examples, mechanism and site of action, therapeutic use, SAR, synthesis. Estrone-sulphatase inhibitors: examples, mechanism and site of action, therapeutic use, SAR.
Progestins: semisynthetic derivatives, androstane and 19-norandrostane derivatives, 17 alfa-hydroxyprogesterone derivatives: examples, mechanism and site of action, therapeutic use, SAR, synthesis.
Androgens, anabolic steroids and antagonists: examples, mechanism and site of action, therapeutic use, SAR. Androgen biosynthesis inhibitors: medrogesterone.
Corticosteroids. Mineralcorticoids: examples, mechanism and site of action, therapeutic use, SAR. Glucocorticoids: examples, mechanism and site of action, therapeutic use, SAR, synthesis.

 

Readings/Bibliography

D.A. WILLIAMS, T.L. LEMKE, Foye's Principi di Chimica Farmaceutica, IV Edizione italiana, Piccin Padova, 2005.

G.L. PATRICK, Introduzione alla Chimica Farmaceutica, EdiSES, Napoli, 2004.

DAVID G. WATSON, Pharmaceutical Chemistry, Churchill Livingstone Elsevier, Edinburgh, 2011.

E. SCHROEDER, C. RUFER, R. SCHMIECHEN, Chimica Farmaceutica, SES 1990.

C. HANSCH, Comprehensive Medicinal Chemistry, vol. I-IV, Pergamon Press,Oxford, 1990.

M.E. WOLFF, Burger's Medicinal Chemistry,Fifith Edition,Wiley Interscience, New York. 1995.

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.
Lesson notes.

Teaching methods

During the lessons all the drug groups will be carefully treated as reported in the course contents.

Assessment methods

During the exstensive course three in itinere  tests concerning the syntheses of  drugs reported in the program are planned.The three in itinere tests are valid if the remaining part of the exam of Medicinal and Toxicological Chemistry II will be taken within six months.

 

Teaching tools

 

Video-projector ( Power Point presentation).

Office hours

See the website of Alberto Chiarini