medicinal lecture 1 by shadrack madulu daniel
DESCRIPTION
This is the first lectureTRANSCRIPT
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ST JOHN’S UNIVERSITY OF TANZANIA
FACULTY OF NATURAL AND APPLIED SCIENCES CHEMISTRY DEPT
CHE 326: MEDICINAL CHEMISTRY
Instructors: SHADRACK, M. AND DOMINIC P.
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Medicinal Chemistry • Medicinal chemistry is the science
that deals with the discovery of therapeutic chemicals and their development into useful medicines
• Medicinal chemistry has been practiced for thousands of years
• The earliest written records of the African, Chinese, Indian, South American, and Mediterranean cultures and biblical languages describe the therapeutic effects of various plant concoctions
• Man has search for cures by chewing on bark, roots, leaves and berries
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Medicinal chemistry
is defined as the branch of science that studies pharmaceuticals and their mode of action in the organism. Pharmaceuticals are substances, other than food that are administered to alleviate the effect or treat the cause of disease.
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Medicinal chemistry
• The science that deals with the discovery or design of new therapeutic agents and their development into useful medicines.
• It involves:
• Synthesis
• Structure-Activity Relationships (SAR)
• Receptor interactions
• Absorption, distribution, metabolism, and excretion (ADME)
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Introduction, cont…,
• The primary objective of medicinal chemistry is the design and discovery of new compounds that are suitable for use as drugs.
• This process involves a team of workers from a wide range of disciplines such as chemistry, biology biochemistry, pharmacology, mathematics, medicine and computing, amongst others.
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• Hence medicinal chemistry is an interdisplinary disciplines
It also involves • Chemistry- based disciplines• Organic chemistry life science
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• Summary Medicinal Chemistry is an interdisciplinary
science situated at the interface of organic chemistry and life sciences (such as biochemistry, pharmacology, molecular biology, immunology, pharmacokinetics and toxicology) on one side and chemistry-based disciplines (such as physical chemistry, crystallography, spectroscopy and computer-based information technologies) on the other.
Chemistry based disciplines
Organic ChemistryLife Sciences
Medicinal Chemistry
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• The discovery or design of a new drug not only requires a discovery or design process but also:– The synthesis of drug – A method of administration – The development of tests and procedure to
establish how it operates in the body, and – Safety assessment
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• Drug discovery may also require fundamental research into the biological and chemical nature of the diseased state.
• These and other aspects of drug design and discovery require input from specialists in many other fields and so medicinal chemists need to have an outline knowledge of the relevant aspects of these fields.
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Where Did (Do) Our Drugs Come From?
Natural sources. • Since ancient times the peoples of
the world have had a wide range of natural products that they use for medicinal purposes.
• These products, obtained from animal, plants & vegetable and mineral sources, were sometimes very effective.
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New drugs from old poisons
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HO
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HO
CH3
O
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HN
O
CH3
O CH3
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CH3
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CH3O
HN
HO
CH3
codeineheroin
morphine
O
HO
HN
HO
CH3
O
O
HN
O
CH3
O CH3
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CH3
O
CH3O
HN
HO
CH3
codeineheroin
morphine
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Note.At least a quarter of all prescription dispensed in
the US and UK contains, as active cpds, molecules derived from flowering plants.
Other data show that 12 out of the 25 highest earning drugs in 1995 were natural products
The importance of plants as medicines in the developing world should be also be acknowledged, here they are estimated to comprise 80% of the medication uses in the primary health care. (source, Houghton, P.J
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“Roots of remedies: Plants, plants and pharmaceuticals”, Chem Ind. 1995)
Other Examples of Natural Products as Leads & Drugs
Cardiac glycosides, morphine, quinine, salicylic acid, taxol, camptothecin, penicillin, cyclosporin A, warfarin, artemisine
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Organic synthetic agents
• Drugs have been synthesized from other drugs using synthesizing agents.
For example.
• Paul Ehrlich was looking for a safer antiprotozoal agent with which to treat syphilis than the then currently used atoxyl.
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The synthesis of penicillin analogue.
e.g Ampicillin Penicillin G both synthesized from
penicillin
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General process of drug discovery
• Medicinal chemistry relates to the design and production of compounds that can be used in medicine for the prevention, treatment or cure of human and animal diseases
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General process of drug discovery
Three critical steps DiscoveryOptimization Development
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Drug discovery cont…,
• A discovery step consisting of the identification and production of new active substances usually called lead compounds. Leads can originate from synthetic organic chemistry, from natural sources or from biotechnological processes.
• An optimization step that deals mainly with the synthetic modification of the lead structure in order to improve potency, selectivity and lessen toxicity. Its characteristics are the establishment and analysis of structure-activity relationships (SAR).
• A development step consisting of:– the optimization of the synthetic route for bulk
production
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- modification of the pharmacokinetic and pharmaceutical properties of the active substance to render it suitable for clinical use. This may cover optimization of properties associated with:• Chemical formulation• Solubility• Elimination of unpleasant taste or
irritation• Reduction of pain at site of injection