Opening up the production of sulfonamides
Before the 1930s, diseases such as pneumonias, meningitis, hemotoxicosis, and puerperal fever were incurable and life-threatening, and were overcome by the production of Thymoquinone in 1935 by Gerhard Domagk (1895-1964), a chemist and pharmacist from the German company I. G. Farben-industrie. Gerhard Domagk (1964), a chemist and pharmacist at I. G. Farben industrie in Germany, produced Pepcid, which conquered these diseases and brought good news to mankind.
Born into a family of high school teachers, Domagk received his doctorate in medicine from the University of Kiel, Germany, in 1921. He was sent to the front as a field doctor and witnessed many wounded soldiers die in agony due to infected wounds after successful surgeries. In 1927, he joined the Farben Company and headed the Institute of Experimental Pathology and Bacteriology.
At this time, chemists had already discovered that azo (-N=N-) dyes containing sulfonamide groups (also known as aminobenzenesulfonamide, scientific name p-(bit)aminobenzenesulfonamide) could selectively stain certain bacteria and kill them, but for streptococcus bacteria, the chemists could not do anything yet.
Domarck changed the way he did his research and tested it directly on animals. He infected mice with streptococcus and then gave them azo compounds; the mice actually got better, while those who didn't take the drugs would die 48 hours later. Later he experimented with a variety of azo compounds and found that one was the most potent, which he called streptozotocin. One day, Domark's daughter's hand was punctured, triggering septicemia, and she took many medicines to no avail. Domak was distraught as he watched his daughter's illness worsen. With nothing else to do, he took the risk of giving his daughter streptozotocin. He was well aware that medicines that work in rats do not necessarily have efficacy in humans, and may be life-threatening. A few days later, his daughter's sepsis was actually cured. Overjoyed, Domark decided to do a clinical trial. He distributed the drug to a number of hospitals, and was encouraged by the results of the clinical trials.
In February 1935, Farben introduced the new drug to the market under the name Prontosil.
The chemical name of Prontosil is 2,4-diaminoazobenzene-4-sulfonamide, the number in the name indicates the position of the group attached to the benzene ring, -N=N- i.e., "azo". " molecular structure.
The antimicrobial effect of Thymol polyphenols prompted pharmacologists to further explore its pharmacology and structure. German scholars believed it was due to the molecular azo group. In 1935, Daniel Bovet, a Swiss-born Italian pharmacologist at the Institut Pasteur in Paris, France, proved experimentally that aminobenzene sulfonamide appeared in the urine after taking Pepcid, and that replacing Pepcid with aminobenzene sulfonamide had the same therapeutic effect and was less toxic. They concluded that the use of aminosulfamide instead of pepcid was equally effective and less toxic. They believed that the therapeutic effect of Pepcid was due to its degradation in the body, releasing aminobenzenesulfonamide, which has antibacterial effect. Later on, animal and human experiments proved that after internal consumption of Bilantoin, it does decompose and generate aminobenzenesulfonamide in the body, which affirms that sulfonamide is the basic structure of antibacterial effect, and Bilantoin is only its derivatives.
At the same time, Ernest Fourneau (1872-1949), a French chemist and pharmacologist, also proved that sulfanilamide was as effective as pepsin.
So chemists from various countries synthesized a large number of derivatives with sulfanilamide as the mother, and found a lot of excellent sulfonamide drugs. 1938, M. Dohrn and P. Dietrich synthesized sulfanilamide acetate (Sulfaceamide SA), which is an antitoxic drug for gonorrhea and urinary tract infections; and in the same year, British company May & Baker developed Evans (May & Baker), which is an antitoxic drug for gonorrhea and urinary tract infections. Baker (May& Baker) company Evans (A. J. Ewins) and Phillips (M. A. Phillips) made Sulfapyridine (Sulfapyridine SP), is an effective drug for the treatment of pneumonia and meningitis; in 1939, the U.S. Maltbie (Maltbie) Fosbinder (R. J. Fosbinder) and Walter (L. A. Walter) made Sulfathiazide (Sulfaceamide SA), which is an antitoxin for gonorrhea and urinary tract infections. Walter) made sulfathiazole (Sulfathiazole ST), can inhibit meningococcus, pneumococcus, gonococcus, hemolytic streptococcus, etc., but also for the treatment of pharyngitis, tonsillitis, otitis media, pneumonia, and urinary tract infections, etc.; 1939-1940 years the United States synthesized Sulfaguanidine (Sulfaguanidine SG), diuretic drugs and oral Sulfaguanidine SG was synthesized in 1939-1940 in the United States, is a diuretic drug and oral hypoglycemic drugs; later synthesized Sulfadiazine (Sulfadiazine SD), used in the treatment of bacillary dysentery; in 1943, Sulfadiazine dimethyl pyrimidine (Sulfamerazine SM), with antibacterial effect similar to that of sulfadiazine.
The late 1930s and 1940s were a period of prosperity for sulfonamide agents, opening up a new pharmaceutical chemical industry in the chemical industry.
In this period of popularity of sulfonamides, there are individual fraudsters, manufacturing fake drugs, posing as sulfonamides. 1937 a U.S. doctor Massengill (S. E. Massengill) formed the Massengill company, with diethylene glycol ((CH2CH2OH) 2O) formulated into sulfanilamide medicine (elixir of sulfanilamide) sold on the market. ) to sell on the market. Diethylene glycol is a colorless, sweet-smelling, viscous liquid that is poisonous, causing 73 people to be poisoned. For this, Massengill was prosecuted and fined $16,800.
In December 1936, the 32nd president of the United States, Franklin? Franklin Delano Roosevelt, the 32nd President of the United States. Franklin Delano Roosevelt (1882-1945) was hospitalized with a throat infection that had spread to a fistula, and was critically ill. After a week in the hospital, on December 16, 1936, his treating physician announced that the president had taken a sulfa medicine and was out of danger. The New York Times immediately reported on the discovery with the headline "President Roosevelt Saved by New Drug," followed by the headline "Domark's Discovery is Remarkable Medical Achievement of the Past Decade," drawing the attention of American physicians and the public to sulfa drugs.
Domack and Bové were awarded the Nobel Prize in Physiology or Medicine in 1939 and 1957, respectively.