1999 Pharmacy Handbook - Medicinal chemistry III

Medicinal chemistry III

Introduction
General objectives
Syllabus
Practical
Textbooks
Assessment

Introduction

Mr John Hurley
44 lectures and 50 hours of practical work.
The aim of the subject is to cover the medicinal chemistry of current therapeutic agents. Aspects that are significant for the practice of pharmacy are emphasised.

General objectives

In this teaching program students are expected to develop:

understanding of the relationship between the chemical structure and biological activity of drugs and endogenous substances; mechanisms of drug action at a molecular level; the physicochemical basis for drug presentation and formulation; absorption, distribution, metabolism and excretion of drugs from a chemical perspective;
abilities in the areas of recognising drug moieties important for drug-receptor interactions; applying chemical rationale to devising alternative forms of drug presentation; using chromatographic techniques for therapeutic drug monitoring;
an appreciation of modern drug design and development; computer-graphics techniques in pharmaceutical science; the chemical basis for drug toxicity and drug interactions; biological applications of spectroscopic techniques.

Syllabus

Drug design. Theories and mechanisms of drug action, drug-receptor interactions, optimisation of drug response, application to recently developed drugs. NMR studies of protein-ligand interactions in drug design.
Drugs affecting the central nervous system. The structure-activity relationships and molecular conformation of CNS transmitter substances, analgesics, sedatives, hypnotics, antipsychotics, anti-Parkinson agents, antidepressants, stimulants and hallucinogenic agents.
Steroids and prostaglandins. Structural relationships and functions of the steroid hormones, glucocorticoids, mineralocorticoids, anti-inflammatory agents, sex hormones, prostaglandins and related agents.
Pharmacodynamic agents. The structure, function and presentation of the following classes of therapeutic agents. Cardiovascular drugs, including antihypertensive inotropic and antiarrhythmic agents, vasodilators, coagulants and anticoagulants, plasma extenders and the diuretic agents. Respiratory tract drugs. Drugs affecting metabolic function, including hypoglycaemic and antithyroid agents. Non-steroidal anti-inflammatory drugs. Antiallergenic agents. Local and general anaesthetics.
Enzyme inhibitors as drugs. This lecture series examines the action of a number of clinically useful enzyme inhibitors with a view to understanding their mode of action. The importance of understanding enzyme mechanisms is emphasised, particularly as related to the rational design of new and specific therapeutic agents.
Detoxifying agents. Chelation therapy in the treatment of heavy-metal poisoning and specific disease states.
Peptides and proteins. The development of the therapeutic potential of peptides and proteins as drugs; structural modifications to endogenous and other peptides leading to increased selectivity, potency and in-vivo stability.
QSAR. The value of non-traditional approaches to drug design; Hammett, Hansch and Taft constants; use of pK_a, partition and hydrolysis data to predict drug stability; multiparameter and non-mathematical approaches. Case studies in the application of QSAR concepts to the development of new drugs. Quinolone antimicrobial agents and atypical antipsychotics.

Practical

Practical classes are designed to provide experience in the synthesis, identification and characterisation of compounds of medicinal interest. The use of analytical and spectroscopic instrumentation in the analysis of drugs and their metabolites. The use of computers in structure- activity relationships and drug design. Emphasis is placed on technique and general methods. Students are expected to show initiative in organising their work. Performance in laboratory classes is taken into account in assessing students' results in this subject. Students are required to wear safety glasses and laboratory coats when attending practical classes in the chemistry laboratories.

Textbooks

Recommended texts

Foye W O Principles of medicinal chemistry 4th edn, Lea and Febiger, 1995
Victorian College of Pharmacy Medicinal chemistry III laboratory manual VCP, 1999

Reference books

Albert A Selective toxicity 7th edn, Chapman and Hall, 1985
Branden C and Tooze J Introduction to protein structure Garland, 1991
Burger's Medicinal chemistry 5th edn, Wiley, 1995-97
Clarke E G C Isolation and identification of drugs 2nd edn, Pharmaceutical Press, 1986
Delgardo J Wilson and Gisvold's 'Textbook of organic medicinal and pharmaceutical chemistry' 9th edn, Lippincott, 1991
Krogsgaard-Larsen P and Bundgaard A (eds) A textbook of drug design and development 2nd edn, Harwood, 1996
Silverman R B The organic chemistry of drug design and drug action 2nd edn, Academic Press, 1996
Smith H J Smith and Williams' 'Introduction to the principles of drug design' 2nd edn, Wright/Butterworths, 1988
Williams D H and Fleming I Spectroscopic methods in organic chemistry 5th edn, McGraw-Hill, 1995

Assessment

Subject assessment will reflect the learning objectives outlined above. Methods of assessment will include:

Mid-year examination (June) (1 hour): 25%
Practical work: 10%
End-of-year examination (2 hours): 65%