As early as BC 1550, the papyrus literature in ancient Egypt recorded that willow leaves could relieve pain. 1763, in the memoirs of Reverend Si Tong published by the Royal Society of London, it was said that grinding willow bark into powder could treat malaria and fever. 1829, French pharmacist Leroux isolated salicin from willow bark for the first time. At that time, Magendie, a doctor and physiologist in Paris, tried salicin and thought it could stop all kinds of fever, no matter what kind, in a day or two.
Salicyloside exists in the bark, branches and leaves of willow and poplar. Salicylic acid is produced after hydrolysis, which makes chemists realize that the medicinal function of willow leaves and willow bark lies in salicylic acid.
1897, F. Hoffman, a researcher from Bayer Company in Germany, treated his father with salicylic acid, which was bitter and brought a burning sensation to his stomach. So he reacted salicylic acid with acetic acid and acetic anhydride, making acetyl group (-—COCH3) in acetic anhydride replace hydrogen (H) in hydroxyl group (-OH) on benzene ring, which may cause burning pain, and become acetylsalicylic acid (CH3CO-).
However, this product and experimental records have been put on hold in Bayer's bookcase for more than a year. It was not until another researcher, Ai Hing Green, personally experimented with this product and invited some doctors to experiment with patients that the leaders of Bayer Company paid attention to it. After pharmacologists identified convincing results, Bayer Company registered in the name of aspirin in February. 1899.
There is not much advertising about the use and promotion of this chemical. At first, it was simply provided to hospitals and doctors for free. But the spread of aspirin and the articles published in medical journals at that time made aspirin a great success and soon spread all over the world. 1900, F. Hoffman obtained a production license from the U.S. Patent Office, which triggered some disputes about aspirin production patents. Britain does not recognize this patent, and the Royal Academy of Sciences claims that F Hoffman only repeated the work of German chemist Kraut around 1860. Until1September 6, 1999, the British news media still published the words of Snead, deputy director of the Department of Pharmacy in university of strathclyde, England: Essien Green, the mentor of F. Hoffman, was the real discoverer of aspirin. F Hoffman only synthesized aspirin under the guidance of eichengreen. In 1934, a year after Nazi rule in Germany, F. Hoffman announced that he was the inventor of aspirin. At that time, eichengreen was trying his best to maintain the factory he founded after leaving Bayer. Later, because of his Jewish ancestry, he was imprisoned in a Nazi concentration camp. It was not until 1949 that eichengreen came out to refute F. Hoffman's lies. Shortly thereafter, eichengreen died.
Aspirin has been used for antipyretic, analgesic and anti-rheumatism for more than 100 years, and its prestige has never diminished. Now people still use it to prevent and treat heart disease. Earlier than it (1887), it became the compound drug APC with the antipyretic and analgesic drug ch 3 conh 6 H4 oc 2h 5 created by another Bayer researcher, with the trade names of phenacetin and caffeine.
At the beginning of the 20th century, chemists studied the relationship between material structure and pharmacology, and began to consciously design and manufacture new chemical drugs. Eyerich, a German biochemist, devoted himself to studying the effects of toxins on the body, in order to find a "panacea" that does not harm the human body but only destroys bacteria. In 1887, he found that basic methyl blue can stain some parasitic bacteria, but not human cells and tissues. He concluded that if the molecule of this dye is combined with some genes that can kill bacteria, it can become a specific drug. 1907, he discovered a trypanosoma red dye, which can dye trypanosoma and kill trypanosoma causing sleeping sickness. He thinks that the effective part of trypanosoma red molecule is azo structure (-—NN—-), so he thinks that the similar structure of arsenic in the periodic table of elements (-—AsAs—-) may also have the same effect. 1in the spring of 909, ehrlich and his assistant, Japanese chemist Qinzuo Shiro, developed the drug 3,3'-diamino-4,4'-dihydroxy arsenic benzene with the number of 606, which is called Solfo powder, which means safe arsenic agent and can kill Treponema pallidum. The less toxic 19 12, 9 14 was synthesized, which was called new sol-fu powder, which effectively treated syphilis that had been popular for a long time at that time and greatly promoted the research of chemistry and pharmacy. 1926, a moth star for malaria control was synthesized in Germany. Like quinine, it has a quinoline mother nucleus. 1930, adipine was synthesized in the United States, and its antimalarial performance was better than quinine. Moreover, it is very cheap. After Japan invaded the origin of quinine in Southeast Asia during World War II, these two drugs, especially adipine, played a great role in the malaria prevention and control of British and American troops.
After 606 and 9 14, the last important compound is sulfonamides. The synthesis of sulfonamides began with the use of Bailang Duoxi, a red azo dye made by Domagk, a chemist and pharmacist of the German French Chemical Company, in 1932. It is 4- sulfanilamide-2,4-diaminoazobenzene. 1935, Domagk discovered the killing effect of Bailangduoxi on Streptococcus, and conducted pharmacological and clinical treatment research. At this time, his daughter's finger was punctured, causing sepsis. Domagk decided to try Bailang Duoxi, and its curative effect has not been determined. After taking the medicine, the symptoms disappeared and she recovered within a few days. In the same year, he obtained a German patent and published a report that Bailandoxi could cure hemolytic streptococcal septicemia, puerperal fever and erysipelas with high mortality at that time, which attracted the attention of scientists all over the world.
The antibacterial effect of Bailangduoxi urges scientists to further explore its pharmacology and structure. German scholars believe that it is caused by azo groups in the molecule. But in fact, it has no bactericidal effect in test tubes. It only works in the body. From 65438 to 0935, the Swiss-born Italian pharmacologist Beauvet and others proved through experiments at the Pasteur Institute in Paris, France, that sulfanilamide appeared in urine after taking paracetamol, and the substitution of sulfanilamide for paracetamol had the same curative effect and less toxicity. Based on this, they believe that the curative effect of Bailangduoxi is due to its degradation in vivo, which releases sulfanilamide and has antibacterial effect.
As a result, scientists from all over the world synthesized a large number of derivatives based on sulfanilamide and found many excellent sulfanilamide drugs. 1938 sulfacetamide synthesized in Germany is an antitoxic drug for gonorrhea and urinary tract infection. In the same year, sulfapyridine was synthesized in Britain, which is an effective drug for treating pneumonia and meningitis. 1939 sulfathiazole produced in the United States is an effective drug for treating pneumococcus and staphylococcus. Then sulfaguanidine and sulfadiazine were prepared, which are intestinal bactericidal drugs and drugs for treating bacillary dysentery respectively. At the end of 1930s and 1940s, sulfonamides developed vigorously, and the synthesis of sulfonamides reached its peak in various countries.
However, fake sulfonamides also appeared during this period. 1937, an American doctor, MAS ngel, founded MAS ngel Company, and used diethylene glycol (CH2 OH) 2O to prepare sulfanilamide panacea, which was sold in the market. Diethylene glycol is a colorless and sweet viscous liquid, which is toxic, thus causing 73 people to be poisoned. In this regard, Mei Sen Gill was sued and fined 16800 USD.
19361945 In February, the 32nd President of the United States, Roosevelt (1882~ 1945), was hospitalized with a throat infection. At that time, the infection had spread to the fistula and he was dying. A week after hospitalization, that is, 1936 12 16, his doctor announced that the president had taken a sulfanilamide and was out of danger. The New York Times immediately reported under the title of "President Roosevelt was saved by new drugs", and then under the title of "Domagk's discovery is an outstanding medical achievement in recent ten years", which aroused the concern of American doctors and the public about sulfonamides.
Domagk and Bowei won the Nobel Prize in Physiology and Medicine with 1939 and 1957 respectively.