Faculty member in charge:
In this course, we will provide the
student with an understanding and appreciation of the influence
chemical structures have on drug action (i.e., structure
Molecular features of drugs
To familiarize the student with molecular
features of drugs relating to (a) their stability in terms of shelf life and
(b) their compatibility in terms of physiochemical and therapeutic
Mechanisms of drug action
To render the student aware of mechanisms
of drug action at the molecular level and to provide insights as to how
physiochemical properties of drugs affect their activity and/or toxicity,
absorption, distribution, metabolism, and excretion;
Design and development of drug entities
To illustrate to the student
the significance of chemical structure, physiochemical properties,
and molecular modification in the rational design and development
of drug entities;
To apprise the student of drug nomenclature,
including generic, proprietary, and chemical designations;
To relate drug chemistry to the principal
therapeutic applications of medicinal agents.
Chapter 1 Introduction
What is medicinal chemistry
How to study medicinal chemistry
How drugs are named
History of medicinal chemistry development
is a scientific discipline at
the intersection of chemistry and pharmacology involved with designing,
synthesizing and developing pharmaceutical drugs. Medicinal chemistry
involves the identification, synthesis and development of new chemical entities
suitable for therapeutic use. It also includes the study of existing drugs, their
biological properties, and their quantitative structure
(QSAR). Pharmaceutical chemistry is focused on quality aspects of medicines
and aims to assure fitness for the purpose of medicinal products.
Medicinal chemistry is a highly interdisciplinary science combining organic
chemistry with biochemistry, computational chemistry, pharmacology,
pharmacognosy, molecular biology, statistics, and physical chemistry.
Activity Relationships (SAR)
Absorption, distribution, metabolism, and excretion (ADME)
. Historial development of medicinal chemistry
Since the mid
th century, pharmaceuticals have moved from the periphery to the
center of health care. In the course of that transition, a new industry sector
expanded to global scope, the field of medicinal chemistry rose to its current
The EARLY TIMES
Chinese emperor Shen Nung
book of herbs, Pen Ts’ao
contains ephedrine; used as a heart stimulant and for asthma. Now
used by body builders and endurance athletes because it quickly converts fat into
energy and increases strength of muscle fibers.
stress and mediator of well
thousands of years.
EMERGENCE OF PHARMACEUTICAL SCIENCE AND INDUSTRY:
The modern pharmaceutical industry traces its origin to two sources:
that moved into wholesale production of drugs such as morphine, quinine, and
strychnine in the middle of the 19th century and
dye and chemical companies
established research labs and discovered medical applications for their products
starting in the 1880s. Merck, for example, began as a small apothecary shop in
Darmstadt, Germany, in 1668, only beginning wholesale production of drugs in
A merging of these two types of firms into an identifiable pharmaceutical industry
took place in conjunction with the emergence of pharmaceutical chemistry and
pharmacology as scientific fields at the end of the 19th century.
Pharmaceutical firms, first in Germany in the 1880s and more recently in the U.S.
and England, established cooperative relationships with academic labs. Postulated
by Paul Ehrlich in 1906 following more than a decade of research, the concept
that synthetic chemicals could selectively kill or immobilize parasites, bacteria,
and other invasive disease
causing microbes would eventually drive a massive
industrial research program that continues to the present.
a chemist at Bayer, Felix Hoffmann, first synthesized aspirin
staple of our medicine cabinets. The end of the 19th century also saw the
development of several important vaccines, including those for tetanus and
Nevertheless, at the start of the 1930s, most medicines were sold without a
prescription and nearly half were compounded locally by pharmacists. While the
medical profession was well
established in Europe and America, the
pharmaceutical industry was only beginning to develop medicines to treat pain,
infectious diseases, heart conditions, and other ailments. Direct application of
chemical research to medicine appeared promising, but only a few substances
newly isolated vitamins and insulin
were more effective than treatments available
at the turn of the century.
THE PHARMACEUTICAL GOLDEN ERA: 1930
The middle third of the 20th century witnessed a blossoming of pharmaceutical
with breakthroughs in the development of synthetic vitamins,
sulfonamides, antibiotics, hormones (thyroxine, oxytocin, corticosteroids, and
others), psychotropics, antihistamines, and new vaccines. Several of these
constituted entirely new classes of medicines.
Deaths in infancy were cut in half,
maternal deaths from infections arising during childbirth declined by more
Illnesses such as tuberculosis, diphtheria, and pneumonia could be
treated and cured for the first time in human history.
in 1945 at a
SOCIAL REASSESSMENT, REGULATION, AND GROWTH:
The pharmaceutical industry was buffeted by significant scientific, medical,
political, and market forces between
. Approaches to drug
discovery and early
stage testing changed as medical advances made it
possible to identify compounds that block specific physiological processes.
Major innovations were made in cardiovascular drugs (starting with
antihypertensives and beta
blockers in the
s, followed by calcium
blockers, ACE inhibitors, and cholesterol
reducing drugs in the
MARKET CHALLENGES, PATIENTS AND ACTIVISTS, AND
During the past two decades, the pharmaceutical industry has brought a new
wave of medicines to market that act on the central nervous system, offer
treatment for viral and retroviral infections (including therapies for
cure or delay the onslaught of cancer
. At the same time,
medicines such as interleukins and interferon
have been able to mimic or
support key features of the immune system.
Within a few years, several thousand biotech companies were founded in the U.S.
The industry went through successive waves of boom and bust; yet by 2005, nearly
1,500 biotech companies were active in the U.S.
The sequence from university spin
off to venture
funded firm to publicly
pioneered so successfully by Genentech
was not followed
universally. For example, by the early 1980s, European countries and the U.S.
shared advanced capital markets, had well
educated scientists and physicians, and
based medical treatment. A biotechnology sector did not
immediately arise across Europe.
Whereas it made sense to speak of an American, German, French, or British drug
company as recently as a decade ago, mergers and greater cross
investments have since rendered such delineation largely irrelevant. Between 1985
and 2005, nearly 40 major mergers produced firms of an unprecedented size and
scope in the pharmaceutical industry.
The scale of
% of GLOBAL
C1.2. Drug nomenclature
A drug usually has 3 names:
Advil, Advil Caplets, Advil, Children's, Cramp End,
Dolgesic, Excedrin IB, Excedrin IB Caplets, Genpril, Genpril Caplets, Haltran,
Ibifon 600 Caplets, Ibren, Ibu, Ibu
8, Ibuprin, Ibuprohm,
Ibuprohm Caplets, Ibu
Tab, Medipren, Medipren Caplets, Midol IB, Motrin,
Motrin Chewables, Motrin, Children's, Motrin, Children's Oral Drops, Motrin
IB Caplets, Motrin, Junior Strength Caplets, Nuprin, Nuprin
Profen, Rufen, Trendar.
Mostly following rules by Chemical Abstracts Service (CAS).
One compound can only have one name, and there is no confusion.
Named by manufactures, one compound can have many different names, and
can be trade marked to protect the brand.
Convenient to remember, needed when apply for registration, cannot be trade
marked or patented. One compound has only one name.
Discovery of New Drugs
Nature is still an excellent source of new drugs
(or precursors of new drugs).
Of the 20 leading drugs in 1999, 9 were derived
from natural products.
1994 almost 40% of the 520 new
drugs approved were natural products or derived
from natural products.
60% of antitumor and anti
infective drugs are
natural products or derived from natural