FUNDAMENTALS OF PHARMACEUTICAL CHEMISTRY
Learning outcomes of the course unit
The course provides the basic notions on the principles of medicinal chemistry, on chemical, physico-chemical, structural aspects and on the mechanism of action of the principal classes of drugs, also providing elements of drug design. Attention is devoted to new drugs whose design and development were based on the application of biotechnological techniques. The application of chemoinformatic and molecular modelling techniques to drug design is also described and discussed.
Prerequisites
Biothermodynamics and Pharmaceutical Biochemistry
Pharmacology
Course contents summary
Principles of medicinal chemistry
Classification of drugs
Naming of drugs
Moments of drug action: pharmaceutical, pharmacokinetic and pharmacodynamic phases
Pharmacokinetics
Drug absorption and distribution, binding to proteins
Drug metabolism: phase I and phase II metabolism
Drug excretion
Prodrugs
Pharmacodynamics
Drug targets and their mechanism of action: receptors, enzymes, nucleic acids, other molecular targets
Affinity, efficacy and potency of drugs
Drug-target interactions
Chemical and physicochemical properties influencing drug action: chemical reactivity, lipophilicity, ionization, solubility.
Structure and biological activity
Physicochemical properties and biological activity: specific and unspecific mechanisms of action
Optical, geometric, conformational isomers and biological activity
Isosteres and bioisosteres
Drug discovery and development
Introduction to quantitative structure-activity relationships: parametrization of biological activity and structure of drugs; extrathermodynamic approach; linear free energy relationships; electronic, steric and lipophilic parameters; simple and multiple linear regression analysis.
Selected examples in medicinal chemistry
Antibacterial Agents: sulfonamides and sulfones, dihydrofolate reductase inhibitors, b-lactam antibiotics and b-lactamase inhibitors, aminoglycosides, quinolones
Antiviral Agents: antimetabolites used against DNA and RNA viruses, phosphonates, antisense therapy; antiviral drugs acting against HIV virus, antiviral drugs acting against cold virus
Antimalarial drugs: sulfonamides, dihydrofolate reductase inhibitors
Anticancer agents: alkylating agents, intercalating agents, antimetabolites, anti-mitotic iagents, monoclonal antibodies, ribozymes.
Recommended readings
G. L. Patrick: "An Introduction to Medicinal Chemistry"; Third Edition, Oxford University Press, Oxford, 2005. ISBN: 0-19-927500-9
D. A. Williams, T. L. Lemke: “Foye’s Principi di Chimica Farmaceutica” PICCIN, Padova, 2005. ISBN: 88-299-1726-5
C. G. Wermuth: "The practice of Medicinal Chemistry" Second Edition, Elsevier Academic Press, Amsterdam, 2003. ISBN: 0-12-744481-5
Teaching methods
The end of course oral exam will cover all the topics of the course. The student has to demonstrate that he/she has understood the basic concepts of each topic.
