Learning objectives
The course is aimed at introducing the students into the basic principles of medicinal chemistry with special regard to the relationships between chemical structure and pharmacological properties. Selected classes of drugs will be described: drugs that act on the peripheral nervous system; cardiovascular, anti-infectious and anticancer drugs.
Prerequisites
The course of Pharmaceutical and Toxicological Chemistry I needs adequate knowledge of Organic Chemistry, Biochemistry and Physiology. The admission to the examination requires the accomplishment of the exam of Biochemistry.
Course unit content
GENERAL SECTION
Discovery and development of drugs.
Definition, classification and nomenclature of drugs. Strategies for drug discovery. Lead compound generation and lead optimization. Molecular variations of the lead. Isosterism and bioisosterism. Structure-activity relationships. QSAR, molecular modeling.
Drug structure and pharmacological activity
Phases of drug action: pharmaceutical, pharmacokinetic and pharmacodynamic phases. Structural and physico-chemical properties of the drugs. Specific and non-specific mechanisms of action. Receptors and drug-receptor interactions. Receptot theories of drugs action. Enzymes and enzyme inhibition. Antimetabolites. Stereochemistry and pharmacological activity. Optical, geometric and conformational isomerism. Pharmacokinetic Drug transport across membranes. Drug metabolism; phase I and phase II reactions; the cytochrome P-450 system. Prodrugs
SYSTEMATIC SECTION
Drugs acting mainly at the peripheral nervous system.
Drugs affecting cholinergic and adrenergic neurotransmission. Classification and therapeutic relevance of cholinergic and adrenergic receptor subtypes. Cholinergic and anticholinergic agents. Anticholinesterases. Nicotinic antagonists. Adrenergic agonists and antagonists.
Cardiovascular drugs
Cardiotonics, antianginal drugs, antiarrhythmic drugs, antihypertensives. Lipid-lowering drugs.
Anti-infectious drugs
Current state of infectious diseases control. Chemiotherapics and antibiotics.
Synthetic systemic anti-infectious drugs. Sulfa drugs, nitro heterocycles, quinolones, oxazolidinones.
Antibiotics. Generality. Beta-lactams (penicillin, cefalosporins, fused-ring and isolated-ring analogs, macrolides (antibacterial macrolides, polyenes, ansamycins), polypeptides, aminoglucosides, tetracyclines, chloramphenicol, miscellaneous antibiotics. Antineoplastic antibiotics.
Antiviral drugs. Generality. Cyclic amines and thiosemicarbazones. Phosphonates
Nucleosides and acyclic nucleosides. Neuroaminidase inhibitors. Antiherpesvirus. Anti-sense oligonucleotides
Anti-AIDS drugs. Generality on the HIV virus and on the antiretroviral agents. Anti-HIV compounds classification: enzyme inhibitors, viral entry inhibitors and inhibitors of gene expression. New developments in anti-HIV treatment.
Antitumor drugs
Cancer chemotherapics. Alkylating agents, DNA-binding drugs. Antimetabolites. Antimitotic drugs. New approaches in cancer treatment. Topoisomerase inhibitors; TK inhibitors. Notes on immunotherapy and on “bio-drugs”.
Bibliography
G.L. Patrick Introduzione alla Chimica Farmaceutica EdiSES – Napoli
D.A. Williams, T.L. Lemke, Foye’s Principi di Chimica Farmaceutica Ed. Piccin Bologna
C.G. Wermuth Le applicazioni della Chimica Farmaceutica EdiSES – Napoli
Assessment methods and criteria
The final exam consists in an oral test focused on all the topics included in the course syllabus. The student must demonstrate that he/she has understood the fundamental concepts of each topic and that he/she is able to use them.
