UNIT I
INTRODUCTION TO
MEDICINAL CHEMISTRY I
Prof. Lakade M. M.
M. Pharm (Quality Assuarance
Techniques)
Points to be covered
• History and development of medicinal chemistry
• Physicochemical properties in relation to biological
action
• Ionization, Solubility, Partition Coefficient, Hydrogen
bonding, Protein binding, Chelation, Bioisosterism,
Optical and Geometrical isomerism
•
Drug metabolism
• Drug metabolism principles- Phase I and Phase II
• Factors affecting drug metabolism
History and Development of Medicinal
Chemistry
Introduction to medicinal chemistry
Medicinal chemistry and pharmaceutical chemistry are
disciplines of chemistry, especially synthetic organic
chemistry, pharmacology and other biological
specialization, where they are involved with design,
chemical synthesis and development of pharmaceutical
agents, or bioactive molecules (drugs).
Medicinal chemistry in its most common practice—focus on
synthetic organic chemistry, natural products and
computational chemistry in close combination with chemical
biology, enzymology and structural biology, together aiming at
the discovery and development of new therapeutic agents.
It also involves the studying of existing drugs, their biological
activity (properties) and their Structure Activity Relationship
(SAR), Mechanism of action, Uses of drugs and Synthesis of
drugs.
Medicinal chemistry studies shows how chemical structure
influences biological activity.
History and development of medicinal
chemistry
There is a long history of plants being used to treat various
diseases.
They figure in the records of early civilizations in Babylon,
Egypt, India and China.
The therapeutic properties of plants were described by the
Ancient Greeks and by the Romans and are recorded in the
writings of Hippocrates and Galenus.
Some metals and metal salts were also used at that time.
The ancient civilizations of the Chinese, the Hindus found to be
that they used therapeutic plants and minerals for the treatment.
They also chewed Coca leaves (containing Cocaine) and used
Mushrooms as Hallucinogenes.
Some natural products used in the history such as Opium,
Cinchona Bark.
In the Middle Ages, various 'Materia Medica and
pharmacopioeas brought together traditional uses of plants.
The 13th -20th century
- Chemical analysis techniques were developed
- Pharmacognosy developed
- Synthesis of chemotherapeutic agents were started.
19th century known as an Age of Innovation and Chemistry.
The herbals of John Gerard (1596), John Parkinson (1640) and
Nicolas Culpeper (1649) provide an insight into this
widespread use of herbs.
Exploration in the seventeenth and eighteenth centuries led to
the addition of a number of useful tropical plants.
General anesthetics like diethyl ether (1842), nitrous oxide
(1845) and chloroform (1847)) where introduced in surgery
from 1842 onwards.
Antiseptics such as iodine (1839) and phenol (1860) also made
an important contribution to the success of surgery. The
hypnotic activity of chloral (trichloroethanal) (1869) was also
reported.
In 1853 Henry mated Morphine with methyl iodide and make
a new substance of Quaternary Salt of Morphine (modified).
Morphine derivative was introduced as cough sedative in
1898.
In 1856 - Kolbe synthesized acetic Acid and
Berthelot synthesized Methane
In 1864 – Barbituric acid synthesized as a useful hypnotic
In 1875- Salicylic Acid were introduced for Typhoid fever
In 1899 – Aspirin was marketed as antipyretic without
unpleasant side effects.
Although the use of willow bark as a pain-killer was known to
the herbalists, the analgesic activity of its constituent salicylic
acid was discovered in the 1870s. p-Hydroxyacetanilide
(paracetamol) and phenacetin (1886) were also recognized as
pain-killers.
Acetylation of salicylic acid to reduce its deleterious effect on
the stomach led to the introduction of aspirin in 1899.
However, its mode of action was not established until 1971.
The local anaesthetic action of cocaine was reported in 1884
although its structure was not known at the time. Various
modifications of cocaine led to discovery of benzocaine (1892)
and procaine (1905).
In the mid-nineteenth century, the first theories of the
relationships between chemical structure and biological
activity began to emerge.
Thus Crum-Brown and Fraser (1869) noted that a 'relationship
exists between the physiological action of a substance and its
chemical composition' leading to the idea that cells can
respond to the signals from specific molecules.
In the 1890s Ehrlich put forward the idea that there were
specific receptors for biologically active compounds and there
exit a lock and key' relationships between them.
20th century saw the recognition of vitamin deficiency
diseases and the elucidation of the structure of various
vitamins. Subsequently synthetic antimalarials such as
pamaquine (1926), mepacrine (1932) and later chloroquine
were introduced as quinine replacements.
A number of developments took place in structures of various
vitamin and structures of various vitamin the 1960s, which
changed medicinal chemistry.
In 1928 (Alexander Fleming)- Discovery of Penicillin which is
1st antibiotic, was an greatest achievement
After 1930 the development of new drug was speeded greatly
by combination of Medicinal Chemistry and experimental
Pharmacology.
In 1940- 1st drug used for beating cancer was Nitrogen
Mustard as an alkylating agent.
It was found that a drug, thalidomide which had been
introduced as a sedative, when used by pregnant women, led to
the birth of deformed children (S isomer). The consequences
of this teratogenic effect brought about a major tightening of
the regulations regarding drug registration and the safety of
medicines.
Secondly in 1964 Hansch published correlations between
substituent effects (Hammett parameters) and the biological
activity of some aromatic compounds. These QSAR began to
provide a framework for the systematic development of drugs
and for decisions to be made in the planning of a research
programme.
Physicochemical Properties In Relation To
Biological Action
PHYSIOCHEMICAL PROPERTIES
The ability of chemical compounds to elicit a pharmacological
or therapeutic effect is related to influence of various physical
and chemical properties of the chemical substances on the
biomolecules that interact with.
In this we know the “role” of some physical and chemical
properties in our body in the biological action.
Physical Properties-Responsible for its action
Chemical Properties- Drug react extra-cellularly according to
simple chemical reactions like neutralization, Chelation,
Oxidation etc.
• Various physiochemical properties are –
a. Ionization of Drug
b. Solubility
c. Partition Coefficient
d. Hydrogen Bonding
e. Protein binding
f. Chelation
g. Bioisosterism
h. Optical and Geometrical isomerism.
