History of Medicinal Chemistry
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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: from: http://www.newworldencyclopedia.org/entry/Ebers_Papyrus 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 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: from: http://www.greekmedicine.net/whos_who/Galen.html http://www.greekmedicine.net/whos_who/Galen.html
Adopted from: from: http://www.greekmedicine.net/whos_who/Hippocrates.html http://www.greekmedicine.net/whos_who/Hippocrates.html
Dioscorides (1st century AD) was the author of the monumental file medica. volume work De materia medica
Adopted from: from: http://www.greekmedicine.net/whos_who/Dioscorides.html http://www.greekmedicine.net/whos_who/Dioscorides.html
The theories and findings of ancient civilizations were propagated by Arabs who invaded Southern Europe in 8 th 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: from: http://www.greekmedicine.net/whos_who/Avicenna.html 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 ph ysician interested in alchemy, urged chemical remedies (antimony, gold and mercury). the use of chemical
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."
http://www.alchemylab.com/paracelsus.htm Adopted from: 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: from: http://botanical.com/botanical/mgmh/p/perbar29.html http://botanical.com/botanical/mgmh/p/perbar29.html
In 18th century, Withering introduced the use of extract of foxglove plants for the treatment treatment of heart failure and d dropsy. ropsy.
Adopted from: from: http://botanical.com/botanical/mgmh/f/foxglo30.html http://botanical.com/botanical/mgmh/f/foxglo30.html
In 19th century many important discoveries were w ere made
1803 (1804, 1805) – morphine was isolated from opium by
German pharmacist F. Sertürner, but the the chemical structure of morphine was not elucidated until 1823.
Adopted from: from: http://toxipedia.org/display/toxipedia/Friedrich+Serturner
Crude opium http://bioweb.uwlax.edu/bio203/s2009/wasicek_lind/Interesting%20facts.htm Adopted from: 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 vitalism organic chemistry.
Adopted from: from: http://en.wikipedia.org/wiki/Friedrich_W%C3%B6hler
1840s – first general anesthetics (N2O, diethylether and
chloroform)) were used chloroform
Re-enactment
of
the
first
public
demonstration of general anesthesia by William T. G. Morton on October 16, 1846 Adopted from: from: http://en.wikipedia.org/wiki/William_T._G._Morton http://en.wikipedia.org/wiki/William_T._G._Morton and http://en.wikipedia.org/wiki/History_of_general_anesthesia http://en.wikipedia.org/wiki/History_of_general_anesthesia
1860s – – phenol phenol was introduced as antiseptic in surgery 1860s
http://www.flickr.com/photos/84195101@N00/3580466645/ Adopted from: from: http://www.flickr.com/photos/84195101@N00/3580466645/ http://www.rsc.org/learn-chemistry/resources/chemistry-in-your-cupboard/dettol/1 http://www.rsc.org/learn-chemistry/resources/chemistry-in-your-cupboard/dettol/1 http://picclick.com.au/Vintage-Calverts-Medical-Soap-Pure-Carbolic-Acid-With191979062764.html#&gid=1&pid=1 191979062764.html#&gid=1&pid=1
Adopted from: from: http://www.npg.org.uk/collections/search/person/mp02756/joseph-lister
1860s 1860s – – 1870s – 1870s – salicylic 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
http://en.wikipedia.org/wiki/Kolbe%E2%80%93Schmitt_reaction Adopted from: 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 from: http://en.wikipedia.org/wiki/Marceli_Nencki
1899 Aspirin Bottle First Bottle of Aspirin Aspirin
Felix Hoffmann from: http://inventors.about.com/library/inventors/blaspirin.htm Adopted from: http://inventors.about.com/library/inventors/blaspirin.htm
The most important discoveries of the 20 th century
Paul Ehrlich was a German physician and scientist who worked
in the fields of hematology, hematology, immunology, and immunology, and chemotherapy. chemotherapy. In
1908 he received a Nobel a Nobel Prize in Physiology or Medicine for his contributions to immunology. Based on his work devoted to staining
of
microorganisms
and
chemotherapeutics, e.g. organoarsenic
body
tissues,
compounds
first against
trypanosomiasiss and syphilis, trypanosomiasi syphilis, were 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 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 were used in therapy.
Frederick Banting and Charles Best in office, 1924 Adopted from: from: http://en.wikipedia.org/wiki/Insulin 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 http://en.wikipedia.org/wiki/Alexander_Fleming Adopted from: 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
http://en.wikipedia.org/wiki/Howard_Florey and Adopted from: from: http://en.wikipedia.org/wiki/Howard_Florey http://en.wikipedia.org/wiki/Ernst_Boris_Chain
1951 – the 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 thirtyfive years, culminating in the massive seventh edition (1985).
Adrien Albert Adopted from: from: http://www.asap.unimelb.edu.au/bsparcs/aasmemoirs/albert.htm 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 discover discovered ed the structure structure of the DNA
molecule and together with Maurice Wilkins were jointly awarded the 1962 Nobel 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/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 http://www.pomona.edu/news/2011/05/11-corwin-hansch.aspx and Adopted from: from: http://www.pomona.edu/news/2011/05/11-corwin-hansch.aspx http://www.amazon.com/Exploring-QSAR-Fundamentals-ApplicationsChemistry/dp/0841229872/ref=sr_1_1?ie=UTF8&qid=1349188035&sr=8-1&keywords=leo+hansch Chemistry/dp/0841229872/ref=sr_1_1?ie=UTF8&qid=1349188035&sr=8-1&keywords=leo+hansch
1970 – Jean-Pierre Jean-Pierre Changeux isolated the nicotinic the nicotinic acetylcholine
receptor of the eel electric eel electric organ, the organ, the first ever isolated membrane pharmacological pharmacologi cal receptor
Jean-Pierre Changeux Adopted from: http://en.wikipedia.org/wiki/Jean-Pierre _Changeux#Nicotinic_recep icotinic_receptor_structure tor_structure http://en.wikipedia.org/wiki/Jean-Pierre_Changeux#N
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 https://www. pinterest.com/Pharmahistorian/pins /Pharmahistorian/pins// http://www.pharmacy.wsu http://www. pharmacy.wsu.edu/history/a%2 .edu/history/a%20history 0history %20of%20pharmacy%20in%20pictures.pdf
http://www.slideshare.net slideshare.net/guest1912478a/pharm /guest1912478a/pharmacy acy http://www. -history-presentation -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://acibis.net/NLI/ViewHtmlEmail.aspx?a=8A2E17607F186E5AC673FD3E1314 C5D0&b=3442AE7E506F749219D440C8F80758E7 C5D0&b=3442AE7E506F749219D440C8F80758E7
http://www.amazon.com/Molecules-That-Changed-WorldNicolaou/dp/3527309837#reader_3527309837 Nicolaou/dp/3527309837#reader_3527309837 http://www.amazon.com/Molecules-Medicine-E-JCorey/dp/0470227494/ref=pd_bxgy_b_img_y/177-51045038298501 8298501
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