History of Medicinal Chemistry

 

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

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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

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(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

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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

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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

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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

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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

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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

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 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

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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

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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

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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

 

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≈

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

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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

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 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 

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ed.; Elis Horwood: Chichester (UK), 1993; 290 pp.

  Sneader, W.  Drug Discovery: a History, 1st  ed.; John Wiley &

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Sons: Chichester (UK), 2005; 468 pp.

  Wermuth, C. G. The Practice of Medicinal Chemistry, 3rd . ed.;

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Elsevier: London (UK), 2008; 121 pp.

  Wermuth, C. G. The Practice of Medicinal Chemistry,4th. ed.;

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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