INTRODUCTION, HISTORY
AND DEVELOPMENT OF
MEDICINAL CHEMISTRY
Ashwini Jadhav
Introduction
Medicinal chemistry- science that deals with the
discovery and design of new therapeutic
chemicals and their development into medicines
Medicines- substances used to treat diseases
Drugs- molecules used as medicines or as
components in medicine to diagnose, mitigate,
cure, treat or prevent disease.
Medicinal chemistry involves-isolation of
compounds from nature or synthesis of new
molecules, investigations of the relationships
between the structure of natural and/or
synthetic compounds and their biological
activities
Introduction
Medicinal chemistry was defined by
IUPAC as ‘ it concerns the discovery, the
development, the identification and the
interpretation of the mode of action of
biologically active compounds at the
molecular level’
Introduction
Medicinal Chemistry is the centre to modern drug
discovery and development.
Medicinal Chemistry studies tell about:
1. How chemical structure influences biological activity.
2. How molecular and physicochemical properties of drug
molecule influences the drug pharmacokinetics and
pharmacodynamics.
Medicinal Chemistry is concerned all about the designing
and development of drug which covers three stages:-
1. Discovery- choice of therapeutic target
2. Optimization- optimization of pharmacodynamics and
pharmacokinetics.
3. Development stage- includes preclinical and clinical
studies.
Drug Discovery
The process of drug discovery begin with the identification of
new, previously undiscovered, biologically active compound
often called ‘hits’ which are found by screening of many
compounds for desired pharmacological properties.
Hits are converted into ‘lead’ and then drug compound is
discovered that undergoes clinical trials.
In medicinal chemistry a chemical compound that shows
promise as a treatment for a disease and may lead to the
development of a new drug called LEAD compound.
Hit
Chemical or functional group modification of hits
LEAD compound
LEAD optimization
LEAD Optimization
It is the process of enhancing the most promising compounds to
improve effectiveness, diminish toxicity, or increase absorption.
The compound to be optimized should have known:
Structure
MOA
Functional groups
Pharmacophore ( the group responsible for pharmacological
activity and having affinity for receptor binding).
LEAD optimization is carried out by modification of functional
group to improve its recognition, affinity, binding geometrics,
pharmacokinetics or its reactivity, stability towards
biotransformation
Optimization results into drug molecule which is safe and
suitable for use in human clinical trials.
Drug Design
Drug development involves-
Patenting of drug
Preclinical trials ( initial biological and
toxicological studies)
Design manufacturing process
Clinical trials
Registration and marketing of the Drug.
History and Development
Therapeutic properties of plants
described by Hippocrates, Dioscorides,
Pliny, Galenus
Metal and metal salts were used
1842 onwards- General anesthetics
introduced- Diethyl ether( 1842), nitrous
oxide (1845), Chloroform (1847)
History and Development
3500BC- Sumerians reported use of opium
3000BC – Chinese reported use of ephedra
1803-Derosome isolated salt from opium
1817- Serturner demonstrated the alkaline nature of
opium
1842- Use of general anesthetic, antiseptics like
iodine and phenol in surgery
1853-Hennery proposed the relationship between
the functional groups, modifiers and their
reactivities
1875- Carl buss isolated salisylic acid from Spirea
ulmaria
History and Development
1884- Phenazone synthesised, local anesthetic
activity of cocaine reported
1890- Hoffman named acetyl salicylic acid as aspirin
1892-Benzocaine was obtained by structural
modification of cocaine
1894- Ehlrich reported lock and key theory
1899-1901- Meyer and overton related distribution
coefficient with biological activity
1910- Barger and dale examined the response of
various tissues to muscarine and nicotine
1911- Barbiturates were introduced as sedatives
History and Development
1920-1930- Identification of vitamin deficiency
diseases and elucidation structure of various
vitamins
1930- structure of steroid hormones
1926-1946-Synthetic antimalarials like
chloroquine were introduced as a substitute of
quinine
1935- Domagk observed antibacterial activity
of sulphonamide dye stuff
1940- Flory and Heaton isolated benzyl
penicillin
