A introduction to the subject of

1. Introduction to Medicinal Chemistry
History and Development of Medicinal Chemistry

2. Medicinal Chemistry
Medicinal Chemistry
is the science which deals with the
discovery and design of
new and better therapeutic chemicals and
the development of these chemicals into
new medicines (drugs)

3. Historically speaking…
•Drug Discovery and development dates back to the early days of
human civilization.
•The earlier drugs or folk medicines were mainly derived from plant
and plant products and supplemented by animal materials and
minerals.
•These drugs were mostly discovered through a combination of trial
and error, experimentation and observation of human and animal
reaction as a result of administration of these products.
•Many ethnic cultures have retained their own folk medicines and both
are used along with modern medicine.

4. Early times
•Ancient traders and travellers also most likely contributed to the
spread of medical knowledge.
•The following are some examples from the early human civilizations
•Chinese medicine
•Egyptian medicine
•Indian medicine
•Greek medicine

5. Indian medicine
•Indian medicine can be traced back 3000 to 5000 years and was
practiced by the Brahmin sages of ancient times.
•Sages and religious leaders were often the administrators of drugs.
•In ancient times, drugs were not used for physical remedies but were
also associated with religious and spiritual healing
•The treatments were set out in sacred writings called Vedas. The
material medica are extensive and are mostly based on herbal
formulations.
•Some of the herbs have also appeared in Western medicines.

6. Foundation of Current Drug Discovery
•The Renaissance period laid the foundation for scientific thoughts in
medicinal preparations and medical treatments.
•Many advances were made in anatomy, physiology, surgery and
medical treatments, including public health care, hygiene and
sanitation.

7. Early 1900s
Despite the advances made in the 1800s, there were only a few drugs available for
treating diseases in the beginning of the 1900s.
• Digitalis – extracted from a plant called foxglove, digitalis stimulates the cardiac
muscles and was used to treat cardiac conditions.
• Quinine – derived from the bark of the Cinchona tree, and was used to treat
malaria.
• Ipecacuanha – extracted from the bark or root of the Cephaelis plant, and was
used to treat dysentery
• Acetyl salicylic acid – Salicin extracted from the bark of the Willow tree was the
lead for aspirin to treat fever
• Mercury – used to treat syphilis.
• Antibiotics – discovery of penicillin, tetracycline, streptomycin

8. Serendipitous Discovery of Penicillin
• Accidental discovery
• Most notable example is discovery of Penicillin by Alexander Fleming in 1928
when working with bacteria Staphylococcus aureus

9. Rational Drug Design
•Rational drug design is a process in which finding of new medication
based on knowledge.
•Rational drug design begins with a initial lead molecule.
•The molecule is systematically modified and tested in various stages
until the desired effect is obtained.

10. Rational drug design - SAR
• Starting from an initial lead, an analogous
set of molecules are synthesized and
tested.
• Knowledge gained is used to systematically
synthesize new molecules till an optimized
lead molecule has been developed.
• This molecule is further optimized in order
to optimize drug-like properties and then
taken for preclinical and clinical testing.

11. Cimetidine story
• Cimetidine is an anti-ulcer drug
• Histamine triggers release of stomach acid. If
uncontrolled, leads to hyperacidity. Chronic acidity
leads to development of stomach ulcers.
• Molecular target for histamine in duodenal cells –
Histamine H2 receptor
• Strategy – Develop a molecule which inhibits
binding of Histamine to H2 receptor
• Molecular requirements for H2 receptor antagonist
• Bind to H2 receptor
• Not trigger the release of stomach acid

12. Systematic modification
• Chemical modification of Histamine- Histamine analogs were synthesized by
systematic chemical modification
• Lead compound – N-guanyl histamine showed some antagonist properties and
was nominated as a lead compound

14. Modern day Drug Discovery

15. Syllabus - Scope of study
•This subject is designed to impart fundamental knowledge on the
structure, chemistry and therapeutic value of drugs.
•The subject emphasizes on structure activity relationships of drugs,
importance of physicochemical properties and metabolism of drugs.
•The syllabus also emphasizes on chemical synthesis of important
drugs under each class.

16. Course Objectives
Upon completion of the course the student shall be able to:
•Understand the chemistry of drugs w.r.t. their pharmacological activity
•Understand the drug metabolic pathways, adverse effect and therapeutic
value of drugs
•Know the Structural Activity Relationship (SAR) of different class of drugs
•Write the Chemical Synthesis of some drugs

19. Medicinal Chemist
• Hit identification
• Designs and synthesizes new chemical entities (NCE)
• Discovers (screens) NCEs
• Studies their effect on a biological processes / mechanisms
• Lead identification - Shortlists Hits
• Lead optimization - Optimises / Changes the structure for
• improving its therapeutic effect
• decreasing side effects
• improving druglikeness / druggability - absorption, distribution, metabolism and
excretion (ADME) of the drug