2.

HISTORY OF MEDICINAL CHEMISTRY

Since the beginning of existence, mankind has attempted to control
diseases using herbs, berries and other substances from the evironment.
Ebers papyrus of Ancient Egypt (ca 1500 BC) includes some 800
recipes and also a number of ritual incantations calling on divine
interventions.

Adopted from: http://www.newworldencyclopedia.org/entry/Ebers_Papyrus

The Egyptians had significant influence on Greeks, and the Greeks in

turn influenced the development of Western medicine.

Significant efforts to combat diseases were made in other great

civilizations namely those of India (Ayurvedic medicine) and China
(Chinese medicine).

The Greeks adopted many Egyptian remedies and tried to rationalize

their use. Outstanding persons of Greek and Roman medicine:
Galen was a propagator of humoral theory that was formulated before
by Hippocrates. According to this theory, an excess or deficiency of
the four humors (blood, phlegm, black bile and yellow bile) resulted in
illness.

Adopted from: http://www.greekmedicine.net/whos_who/Galen.html

Adopted from: http://www.greekmedicine.net/whos_who/Hippocrates.html

Dioscorides (1st century AD) was the author of the monumental file
volume work De materia medica.
 Adopted from: http://www.greekmedicine.net/whos_who/Dioscorides.html

The theories and findings of ancient civilizations were propagated by

Arabs who invaded Southern Europe in 8th century. The Arabs added
the use of metallic salts to the pharmacopoeia.
Avicenna (born in 890 A. D. as Hakim Ibn Sina) has been considered
Father of Modern Medicine.
 Adopted from: http://www.greekmedicine.net/whos_who/Avicenna.html

In renaissance period, travelling Jewish physicians introduced ideas of

Dioscorides and Galen into medicinal usage, and there was a great
upsurge in the medicinal use of herbs.

In the 16th century, Paracelsus, a physician interested in alchemy, urged

the use of chemical remedies (antimony, gold and mercury).
He is also known as the father of toxicology due to his idea that
"Everything is poison, there is poison in everything. Only the dose
makes a thing not a poison."

Adopted from: http://www.alchemylab.com/paracelsus.htm

In the 17th century, Jesuit missionaries brought an extract of the
cinchona bark from the South America to Europe. Two centuries later
(1820) its active principle, quinine, was isolated.

Adopted from: http://botanical.com/botanical/mgmh/p/perbar29.html

In 18th century, Withering introduced the use of extract of foxglove

plants for the treatment of heart failure and dropsy.

Adopted from: http://botanical.com/botanical/mgmh/f/foxglo30.html

In 19th century many important discoveries were made

 1803 (1804, 1805) – morphine was isolated from opium by
German pharmacist F. Sertürner, but the chemical structure of
morphine was not elucidated until 1823.
 Adopted from: http://toxipedia.org/display/toxipedia/Friedrich+Serturner

Crude opium
Adopted from: http://bioweb.uwlax.edu/bio203/s2009/wasicek_lind/Interesting%20facts.htm

 1828 – Friedrich Wöhler synthesized urea from inorganic salt

(ammonium cyanate). It became obvious that organic compounds
can be obtained not only from natural sources, but also by means
of synthetic procedures. This finding meant the overcoming of
vitalism and was the basis of the development of synthetic
organic chemistry.
 Adopted from: http://en.wikipedia.org/wiki/Friedrich_W%C3%B6hler

 1840s – first general anesthetics (N2O, diethylether and

chloroform) were used

Re-enactment of the first public

demonstration of general anesthesia by
William T. G. Morton on October 16, 1846
Adopted from: http://en.wikipedia.org/wiki/William_T._G._Morton and
http://en.wikipedia.org/wiki/History_of_general_anesthesia

 1860s – phenol was introduced as antiseptic in surgery

 Adopted from: http://www.flickr.com/photos/84195101@N00/3580466645/
http://www.rsc.org/learn-chemistry/resources/chemistry-in-your-cupboard/dettol/1
http://picclick.com.au/Vintage-Calverts-Medical-Soap-Pure-Carbolic-Acid-With-
191979062764.html#&gid=1&pid=1

Adopted from: http://www.npg.org.uk/collections/search/person/mp02756/joseph-lister

 1860s – 1870s – salicylic acid started to be used first as internal
antiseptic drug and later also as antipyretic and antirheumatic
agent

Kolbe-Schmidt synthesis of salicylic acid Hermann Kolbe

Adopted from: http://en.wikipedia.org/wiki/Kolbe%E2%80%93Schmitt_reaction
and http://en.wikipedia.org/wiki/Adolph_Wilhelm_Hermann_Kolbe

 Other derivatives of salicylic acid followed in the second half of

19th century, namely phenyl salicylate (prepared by M. Nencki
and marketed as Salol) and acetylsalicylic acid (prepared by
F. Hoffmann and marketed as Aspirin).

Phenyl salicylate is a prodrug

and hydrolyses to salicylic
acid and phenol in the body
Marceli Nencki
Adopted from: http://en.wikipedia.org/wiki/Marceli_Nencki
 1899 Aspirin Bottle First Bottle of
Aspirin

Felix Hoffmann
Adopted from: http://inventors.about.com/library/inventors/blaspirin.htm

The most important discoveries of the 20th century

 Paul Ehrlich was a German physician and scientist who worked
in the fields of hematology, immunology, and chemotherapy. In
1908 he received a Nobel Prize in Physiology or Medicine for his
contributions to immunology. Based on his work devoted to
staining of microorganisms and body tissues, first
chemotherapeutics, e.g. organoarsenic compounds against
trypanosomiasis and syphilis, were obtained. He also promoted
the concept of "magic bullets", i.e. substances that would only
affect the invading cells that caused disease, but not harm the body
as well. Unfortunately, to get a magic bullet is difficult, and
currently available drugs always have both desired effect and side
effects.
 Paul Ehrlich
Adopted from: http://en.wikipedia.org/wiki/Paul_Ehrlich
http://www.nobelprize.org/nobel_prizes/medicine/laureates/1908/ehrlich-bio.html

 At the beginning of 1920s, first purified animal-source insulin

preparations were used in therapy.

Frederick Banting and Charles Best in office, 1924

Adopted from: http://en.wikipedia.org/wiki/Insulin

 In 1928, Alexander Fleming accidentally discovered the first

antibiotic penicillin, but he was not able to produce sufficient
amount.
 Alexander Fleming
Adopted from: http://en.wikipedia.org/wiki/Alexander_Fleming

Moreover, sulfonamides were introduced in the mid 1930s as

effective antibacterial chemotherapeutics. Hence the penicillin
mass production and practical usage only started at the beginning
1940s thanks to Howard Florey and Ernst Chain.

Howard Florey Ernst Chain

Adopted from: http://en.wikipedia.org/wiki/Howard_Florey and
http://en.wikipedia.org/wiki/Ernst_Boris_Chain

 1951 – the book Selective Toxicity: The Physico-Chemical Basis

of Therapy was by published by Adrien Albert. In this book he
tried to explain the ability of chemical substances to affect certain
cells without harming others, applying the principle not only to
 human and veterinary medicine, but to pesticides and herbicides.
The concept probably was Albert’s greatest contribution to the
progress of medicinal chemistry and bioorganic chemistry. The
original small edition was gradually extended over the next thirty-
five years, culminating in the massive seventh edition (1985).

Adrien Albert
Adopted from: http://www.asap.unimelb.edu.au/bsparcs/aasmemoirs/albert.htm

 1952 – chlorpromazine was introduced as antipsychotic drug

followed by many other compounds that affect central nervous
system.
 1953 – Watson and Crick discovered the structure of the DNA
molecule and together with Maurice Wilkins were jointly
awarded the 1962 Nobel Prize for Physiology or Medicine

Francis Crick
James Dewey Watson
 Maurice Wilkins
Adopted from:
http://en.wikipedia.org/wiki/James_D._Watson,
http://en.wikipedia.org/wiki/Francis_Crick
http://en.wikipedia.org/wiki/Maurice_Wilkins

 ≈ 1960 – Corwin Hansch introduced Quantitative Structure

Activity Relationships (QSARs) which allow chemists to modify
drugs and other molecules in a predictable manner to achieve
desired characteristics, and laid the basis for computer-assisted
molecule design

Corwin Hansch
Adopted from: http://www.pomona.edu/news/2011/05/11-corwin-hansch.aspx and
http://www.amazon.com/Exploring-QSAR-Fundamentals-Applications-
Chemistry/dp/0841229872/ref=sr_1_1?ie=UTF8&qid=1349188035&sr=8-1&keywords=leo+hansch
  1970 – Jean-Pierre Changeux isolated the nicotinic acetylcholine
receptor of the eel electric organ, the first ever isolated membrane
pharmacological receptor

Jean-Pierre Changeux
Adopted from:
http://en.wikipedia.org/wiki/Jean-Pierre_Changeux#Nicotinic_receptor_structure

 1982 – recombinant human insulin was introduced as the first

biological drug

There are many other important discoveries and drugs that could not be
mentioned in this lecture. If you want to know more go to

http://historyofdrugs.net/

https://www.pinterest.com/Pharmahistorian/pins/

http://www.pharmacy.wsu.edu/history/a%20history

%20of%20pharmacy%20in%20pictures.pdf
http://www.slideshare.net/guest1912478a/pharmacy

-history-presentation

or consult the books

 Taylor, J. B.; Kennewell, P. D. Modern Medicinal Chemistry, 1st
ed.; Elis Horwood: Chichester (UK), 1993; 290 pp.
 Sneader, W. Drug Discovery: a History, 1st ed.; John Wiley &
Sons: Chichester (UK), 2005; 468 pp.
 Wermuth, C. G. The Practice of Medicinal Chemistry, 3rd. ed.;
Elsevier: London (UK), 2008; 121 pp.
 Wermuth, C. G. The Practice of Medicinal Chemistry,4th. ed.;
Elsevier: London (UK), 2015; 1024 pp.
http://ac-
ibis.net/NLI/ViewHtmlEmail.aspx?a=8A2E17607F186E5AC673FD3E1314
C5D0&b=3442AE7E506F749219D440C8F80758E7

http://www.amazon.com/Molecules-That-Changed-World-
Nicolaou/dp/3527309837#reader_3527309837

http://www.amazon.com/Molecules-Medicine-E-J-
Corey/dp/0470227494/ref=pd_bxgy_b_img_y/177-5104503-
8298501