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Faculty of Pharmacy
Medicinal Chemistry
MCHM 311
Siddieg Omer Elsiddieg, M. Sc,
B. Sc (Honors)
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Class Contents
Introduction to Medicinal Chemistry
Physicochemical Properties of Drugs in Relation to
Biological Activities
Receptors: Structures and Functions
Principles of Drug Design
Drug Metabolism
Factors Influencing Drug Metabolism
Toxic Effects of Drug Metabolism
What Is Medicinal Chemistry?
“ A chemistry-based discipline, involving aspects of
biological, medical and pharmaceutical sciences. It is
concerned with the invention, discovery, design,
identification, and preparation of biologically active
compounds, the study of their metabolism, the
interpretation of their mode of action at the molecular
level and the construction of structure activity
relationships (SARs), the relationship between chemical
structure and pharmacological activity for a series of
compounds.”
“is the applied science that is focused on the design (or
discovery) of new chemical entities (NCEs) and their
optimization and development as useful drug
molecules for the treatment of disease processes”.
In achieving this mandate, the medicinal chemist must:
Design and synthesize new molecules.
Ascertain how they interact with biological
macromolecules (such as proteins or nucleic acids).
Elucidate the relationship between their structure
and biological activities.
Determine their absorption and distribution
throughout the body.
Evaluate their metabolic transformations.
Medicinal Chemistry is Interdisciplinary:
Theoretical Chemistry
Organic Chemistry
Analytical Chemistry
Molecular Biology
Pharmacology
Biochemistry
Bottom Line:
Design and synthesis of new drugs
How Did we Arrive Here?
A brief History of Medicinal Chemistry
Ideas, tools, and knowledge that advanced contemporary
medicinal chemistry
Drugs of Antiquity
Fats, Oils, honey, wax and milk were used
Mud, and Salts were used for wound dressing
Fried Ox Liver for blidness
The Middle Ages
The use of Antimony salts as alixirs
The Nineteenth Century
Expansion of chemical knowledge
Focus on finding the active ingredients in the plants
and animal remedies (e.g. isolation of morphine).
Increased use of pure substances
Birth of pharmaceutical industry
The twentieth Century
Domagk discovery of sulfa drugs (Prontosil)
Discovery of penicillin
Modern medicinal chemistry
What are Drugs?
A drug molecule possesses one or more functional
groups positioned in three-dimensional space on a
structural framework that holds the functional groups
in a defined geometrical array that enables the
molecule to bind specifically to a targeted biological
macromolecule, the receptor.
The structure of the drug molecule thus permits
a desired biological response, which should be
beneficial (by inhibiting pathological processes) and
which ideally precludes binding to other untargeted
receptors, thereby minimizing the probability of
toxicity.
The framework upon which the functional groups are
displayed is typically a hydrocarbon structure (e.g.,
aromatic ring, alkyl chain) and is usually chemically
inert so that it does not participate in the binding
process. The structural framework should also be
relatively rigid (“conformationally constrained”) to
ensure that the array of functional groups is not
flexible in its geometry, thus preventing the drug
from interacting with untargeted receptors by altering
its
molecular shape
To be successful in countering a disease process,
however, a drug molecule must have additional
properties beyond the capacity to bind to a defined
receptor site.