PLACEBO to Discovery & Development of Organic Medicinal Chemicals

Placebo effect

A phenomenon when a patient receives a placebo treatment will have a perceived or actual improvement of medical condition

Pharmacophore

the region of the molecule containing the essential organic functional groups that directly interact with the receptor active site and, therefore, confers the biologic activity of interest

• Physicochemical properties used to develop new pharmacologically active compounds;
• Their mechanism of action;
• The drug's metabolism;
• Possible biological activities of the metabolites;
• Importance of stereochemistry in drug design;
• The methods used to determine what “space” a drug occupies.

Considerations in understanding the principles of medicinal chemistry:

Cimetidine

• as an antinuclear antibody test/drug

• study of the changes in antagonism of H₂ -histamine receptors induced by varying the physical properties of structure based on histamine.

Receptors

• substance to which a drug needs to interact with to elicit pharmacologic response

• a relatively small region of a macromolecule which may be an/a: enzyme, structural or functional group/component of CM, specific intracellular substance such as proteins and nucleic acids.

Random sampling/screening of higher plants

Traditionally, how drugs are discovered?

Random screening

(with enzyme linked assays or receptors from gene cloning) of existing drugs lead to identification of new LEAD drug.

• e.g. Amantadine

Rational Drug Design

• refers to a process in which finding of new medication is based on knowledge of biological target is done

• involves design of small molecules that are complementary in shape and charge to the biomolecular target.

• Begins with hypothesis that modulation of a specific biological target may have therapeutic value.

• X-ray crystallography

• Nuclear magnetic resonance

• Molecular graphics

• Computational chemistry

opposite approach to high-volume screening using techniques like: Rational Drug Design

• HIV protease inhibitor

• ACE inhibitors

• H 2 antagonists

Leads to the development of drugs;

Categories of Rational Drug Design

• Development of small molecules with desired properties for targets, biomolecules has functional roles in cellular processes and 3D structural information

• Development of small molecules with predefined properties for targets, whose cellular functions and their structural information maybe known or unknown.

• Random Screening

• Molecular Manipulation

• Molecular Designing

• Drug Metabolites

• Serendipity

Strategies/Methods of Drug Discovery

Serendipity

• Penicillin

• 5-FU

• Minoxidil

• Sildenafil

• Levodopa

• Chlorpromazine

• LSD by Albert Hofmann “acid trip”

• “Mustine” = mustard gas

• Nitrous oxide

Albert Hofmann

LSD “acid trip”

Mustine

mustard gas