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Trimethoprim Produkt Beschreibung

Trimethoprim Struktur
738-70-5
CAS-Nr.
738-70-5
Bezeichnung:
Trimethoprim
Englisch Name:
Trimethoprim
Synonyma:
Ipral;5-(3,4;Baktar;Tiempe;wr5949;abaprim;bw56-72;NIH 204;Trimpex;Uretrim
CBNumber:
CB2745185
Summenformel:
C14H18N4O3
Molgewicht:
290.32
MOL-Datei:
738-70-5.mol

Trimethoprim Eigenschaften

Schmelzpunkt:
199-203 °C
Siedepunkt:
432.41°C (rough estimate)
Dichte
1.1648 (rough estimate)
Brechungsindex
1.6000 (estimate)
storage temp. 
2-8°C
Löslichkeit
DMSO: soluble
pka
6.6(at 25℃)
Aggregatzustand
white powder
Farbe
colorless or white
Wasserlöslichkeit
<0.1 g/100 mL at 24 ºC
Merck 
14,9709
BRN 
625127
Stabilität:
Stable. Incompatible with strong oxidizing agents, acids.
CAS Datenbank
738-70-5(CAS DataBase Reference)
NIST chemische Informationen
Trimethoprim(738-70-5)
EPA chemische Informationen
Trimethoprim (738-70-5)
Sicherheit
  • Risiko- und Sicherheitserklärung
  • Gefahreninformationscode (GHS)
Kennzeichnung gefährlicher T
R-Sätze: 25
S-Sätze: 45-24/25
RIDADR  3249
WGK Germany  3
RTECS-Nr. UV8225000
8-10-21
HazardClass  6.1(b)
PackingGroup  III
HS Code  29335995
Giftige Stoffe Daten 738-70-5(Hazardous Substances Data)
Toxizität LD50 orally in mice: 7000 mg/kg (Yamamoto)
Bildanzeige (GHS)
Alarmwort
Gefahrenhinweise
Code Gefahrenhinweise Gefahrenklasse Abteilung Alarmwort Symbol P-Code
H227 Combustible liquid Flammable liquids Category 4 Warnung P210, P280, P370+P378, P403+P235,P501
Sicherheit
P403+P235 An einem gut belüfteten Ort aufbewahren. Kühl halten.

Trimethoprim Chemische Eigenschaften,Einsatz,Produktion Methoden

R-Sätze Betriebsanweisung:

R25:Giftig beim Verschlucken.

S-Sätze Betriebsanweisung:

S45:Bei Unfall oder Unwohlsein sofort Arzt zuziehen (wenn möglich, dieses Etikett vorzeigen).

Beschreibung

Trimethoprim selectivity between bacterial and mammalian dihydrofolate reductases results from the subtle but significant architectural differences between these enzyme systems. Whereas the bacterial enzyme and the mammalian enzyme both efficiently catalyze the conversion of dihydrofolic acid to tetrahydrofolic acid, the bacterial enzyme is sensitive to inhibition by trimethoprim by up to 40,000-fold lower concentrations than the mouse enzyme is. This difference explains the useful selective toxicity of trimethoprim.

Chemische Eigenschaften

Crystalline

Originator

Eusaprim,Wellcome,Italy,1970

Verwenden

anti-inflammatory

Verwenden

An antibacterial agent which selectively inhibits dihydrofolate reductase.

Manufacturing Process

6 grams (0.26 mol) sodium was dissolved in 300 ml methanol under stirring and refluxing. 47.5 grams (0.55 mol) β-methoxypropionitrile and 98 grams (0.5 mol) 3,4,5-trimethoxybenzaldehyde were added and the mixture refluxed gently for 4 hours. The mixture was then chilled and 150 ml of water was added. The product crystallized rapidly. Crystallization was allowed to proceed at 5° to 10°C under stirring for 1 hour. The product was filtered by suction and washed on the filter with 200 ml of 60% ice cold methanol. The crude material was air-dried and used for further steps without purification. It melted at 78° to 80°C. A pure sample, recrystallized from methanol, melted at 82°C. The yield of 3,4,5-trimethoxy-2'-methoxymethylcinnamonitrile was 92 grams, corresponding to 70% of the theory.
19 grams (0.83 mol) sodium was dissolved in 300 ml methanol, 106 grams of 3,4,5-trimethoxy-2'-methoxymethylcinnamonitrile was added and the mixture gently refluxed for 24 hours. The solution, which had turned brown, was poured into 1 liter of water and the precipitated oil extracted repeatedly with benzene. The combined benzene layers (500 to 700 ml) were washed 3 times with 500 ml of water, the benzene removed by evaporation in a vacuum from a water bath, and the brown residual oil distilled in vacuo, boiling point 215° to 225°C/11 mm. The clear, viscous oil, 3,4,5-trimethoxy-2'-cyano_x0002_dihydrocinnamaldehyde dimethyl acetal, weighed 83 grams (71% of the theory), and showed a nD23 = 1.5230. It solidified upon standing. A sample recrystallized from methanol melted at 69° to 70°C and showed a strong melting point depression with the starting material; nD25 = 1.5190. 31.5 grams (0.107 mol) 3,4,5-trimethoxy-2'-cyano-dihydrocinnamaldehyde dimethyl acetal was refluxed with methanolic guanidine solution (200 ml containing 0.25 mol of guanidine) for 2 hours. The methanol completely distilled off under stirring, finally from a bath of 110° to 120°C until the residue solidified completely to a yellowish crystalline mass. After allowing to cool, it was slurried with 100 ml of water and collected by vacuum filtration and dried. The yield of 2,4-diamino-5-(3,4,5-trimethoxybenzyl)pyrimidine amounted to 28 grams (91% of the theory). The material showed the correct melting point of 199° to 200°C and was, however, yellowish discolored. 20 grams of the above product was added to 30 ml of 3 N aqueous sulfuric acid at 60°C under stirring. The solution was chilled under stirring to 5° to 10°C. The crystalline sulfate was collected by vacuum filtration and washed on the filter twice with 10 ml of cold 3 N aqueous sulfuric acid each time. From the filtrate there was recovered 1.3 grams (6.5%) of discolored material melting at 195° to 196°C and which can be added to subsequent purification batches.
The sulfate on the filter was dissolved in 200 ml of hot water, the solution charcoaled hot, and the product precipitated from the clear colorless filtrate by the gradual addition of a solution of 20 grams of sodium hydroxide in 40 ml of water under chilling. The precipitate was filtered by suction and washed thoroughly with water on the filter. The white material, 17.5 grams (88%) showed the correct melting point of 200° to 201°C, according to US Patent 3,341,541.

Trademarks

Proloprim (Monarch); Trimpex (Roche).

Therapeutic Function

Antibacterial (urinary)

Antimicrobial activity

Trimethoprim has a broad spectrum of antimicrobial activity. It is 20–100 times more active than sulfamethoxazole with respect to most bacterial forms. Trimethoprim is active with respect to Gram-positive, aerobic bacteria such as Staphylococcus aureus, Staphylococcus epidermidis, and various types of Streptococcus and Listeria monocytogenes. Trimethoprim is inferior to sulfonamides against forms of Nocardia. It is active with respect to Gram-negative, aerobic bacteria such as most E. coli, Enterobacter, Proteus, Klebsiella, Providencia, Morganella, Serratia marcescens, Citrobacter, Salmonella, Shigella, Yersinia enterocolitica that are sensitive to trimethoprim. Trimethoprim is also active with respect to Legionella, Acinetobacter, Vibrio, Aeromonas, Pseudomonas maltophila, P. cepacia, although P. aeruginosa is resistant to trimethoprim.

Allgemeine Beschreibung

Odorless white powder. Bitter taste.

Air & Water Reaktionen

Insoluble in water.

Reaktivität anzeigen

Trimethoprim readily forms salts with acids. .

Brandgefahr

Flash point data for Trimethoprim are not available. Trimethoprim is probably combustible.

Mechanism of action

Haemophilus influenzae and H. ducreyi are sensitive to trimethoprim. Pathogenic Neisseria (meningococci and gonococci) and Branhamella catarrhalis are moderately resistant to trimethoprim, although they are very sensitive to a combination of trimethoprim and sulfamethoxazole. Anaerobic bacteria in general are resistant to trimethoprim, although a combination of trimethoprim-sulfamethoxazole does have an effect on them. Pneumocystis carinii is also sensitive to that combination.
Bacterial resistance to trimethoprim can originate because of a number of reasons: inability of the drug to penetrate through the membrane (P. aeruginosa); the presence of dihydrofolate reductase that is not sensitive to inhibition by trimethoprim; overproduction of dihydrofolate reductase and mutation expressed as thyminic dependence, when the organism requires exogenic thymine for synthesizing DNA, i.e. bypassing metabolic blockage caused by trimethoprim.
Resistance to a combination of trimethoprim-sulfamethoxazole is always less frequent than when any of these drugs is used separately. This combination of drugs, which is known by the commercial names cotrimoxazole, bactrim, biseptol, sulfatrim, and many others, is used for treating infections of the respiratory tract, infections of the urinary tract, gastric infections, surgical infections, enteritis, meningitis, and other diseases.

Clinical Use

Trimethoprim (5-[(3,4,5-trimethoxyphenyl)methyl]-2,4-pyrimidinediamine or 2,4-diamino-5-(3,4,5-trimethoxybenzyl)pyrimidine) is closely related to several antimalarialsbut does not have good antimalarial activity by itself; it is,however, a potent antibacterial. Originally introduced incombination with sulfamethoxazole, it is now available as asingle agent.
Approved by the FDA in 1980, trimethoprim as a singleagent is used only for the treatment of uncomplicatedurinary tract infections. The argument for trimethoprim asa single agent was summarized in 1979 by Wormser andDeutsch. They point out that several studies comparingtrimethoprim with TMP–SMX for the treatment ofchronic urinary tract infections found no statistically relevantdifference between the two courses of therapy.The concern is that when used as a single agent, bacterianow susceptible to trimethoprim will rapidly developresistance. In combination with a sulfonamide, however,the bacteria will be less likely to do so. That is, they willnot survive long enough to easily develop resistance toboth drugs.

Chemical Synthesis

Trimethoprim, 2,4-diamino-5-(3,4,5-trimethoxybenzyl)pyrimidine (33.1. 51), is synthesized in various ways. The first scheme of synthesis begins with ethyl ester of 3,4,5-trimethoxydehydrocinnamic acid, which is formylated with ethyl formate using sodium as a base to make an enol of the semialdehyde 3,4,5-trimethoxybenzylmalonic ester (33.1.49), which undergoes a heterocyclization reaction with guanidine to make 2-amino- 4-hydroxy-5-(3,4,5-trimethoxybenzyl)pyrimidine (33.1.50). Subsequent replacement of the hydroxyl group in the resulting product with chlorine using phosphorous oxychloride and then with an amino group using ammonia gives the desired trimethoprim.

All of the other syntheses begin with 3,4,5-trimethoxybenzaldehyde. According to one of them, condensation of 3,4,5-trimethoxybenzaldehyde with 3-ethoxy- or 3-anilinopropionitrile gives the corresponding benzylidene derivative (33.1.52), which upon direct reaction with guanidine gives trimethoprim.

Trimethoprim has also been synthesized by condensing 3,4,5-trimethoxybenzaldehyde with malonic acid dinitrile in a Knoevenagel reaction, which forms the derivative (33.1.53), which is partially reduced to the enamine (33.1.54) by hydrogen using a palladium on carbon catalyst, which upon being reacted with guanidine is transformed into trimethoprim.

Finally, trimethoprim can be synthesized in a manner that also uses a Knoevenagel condensation of 3,4,5-trimethoxybenzaldehyde as the first step, but this time with ethyl cyanoacetate, which gives an ylidene derivative (33.1.55). The double bond in this product is reduced by hydrogen over a palladium on carbon catalyst, giving 3,4,5-trimethoxybenzylcyanoacetic ester (33.1.56). Reacting this in a heterocyclization reaction with guanidine gives the desired trimethoprim.

Trimethoprim Upstream-Materialien And Downstream Produkte

Upstream-Materialien

Downstream Produkte


Trimethoprim Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

Global( 427)Lieferanten
Firmenname Telefon Fax E-Mail Land Produktkatalog Edge Rate
PI & PI BIOTECH INC.
18371201331
020-81716319 Sales@pipitech.com CHINA 3048 55
Henan Tianfu Chemical Co.,Ltd.
0371-55170693
0371-55170693 info@tianfuchem.com CHINA 22617 55
Hangzhou FandaChem Co.,Ltd.
0086 158 5814 5714 (Mobile
+86-571-56059825 fandachem@gmail.com CHINA 8463 55
Hubei XinRunde Chemical Co., Ltd.
+8615102730682
02783214688 bruce@xrdchem.cn CHINA 568 55
Hefei TNJ Chemical Industry Co.,Ltd.
86-0551-65418684 18949823763
86-0551-65418684 info@tnjchem.com China 2799 55
career henan chemical co
+86-371-86658258
sales@coreychem.com CHINA 30021 58
Hebei Ruishun Trade Co.,LTD
17052563120
Mike@rsbiology.com CHINA 301 58
Hubei Jusheng Technology Co.,Ltd.
86-18871470254
027-59599243 linda@hubeijusheng.com CHINA 28230 58
Hebei Jimi Trading Co., Ltd.
+86 319 5273535
bestoneforyou@sina.com CHINA 293 58
Accela ChemBio Inc.
(+1)-858-699-3322
(+1)-858-876-1948 info@accelachem.com United States 19969 58

738-70-5(Trimethoprim)Verwandte Suche:


  • methoxybenzyl aminopyrimidine
  • Trimethopim(TMP)
  • TRIMETHOPRIM, CRYSTALLIZED
  • TRIMETHOPRIM VETRANAL, 250 MG
  • 5-(3,4,5-trimethoxybenzyl)pyrimidine-2,4-diyldiamine
  • Antibiotic synergist
  • trimethoprim crystalline
  • TRIMETHOPRIM BP
  • Trimethorim
  • 5-(3,4,5-trimethoxybenzyl)pyrimidine-2,4-diamine(Trimethoprim)
  • TRIMETHOPRIMUM
  • 5-((3,4,5-trimethoxyphenyl)met
  • TRIMETHOPRIM,MICRONIZED,USP
  • TRIMETHOPRIM,POWDER,USP
  • TRIMETHOPRIM USP
  • 5-(3,4
  • AZT + TMP/SMX (mixture) combination
  • Proloprim (TN)
  • Trimpex (TN)
  • TRIMETHOPRIM CRYSTALLIZED, >= 99.0%
  • TRIMETHOPRIM, >=98% (HPLC)
  • abaprim
  • 5-((3,4,5-trimethoxyphenyl)methyl)-2,4-pyrimidinediamine
  • 5-(3,4,5-trimethoxybenzyl)-2,4-diaminopyrimidine
  • 5-(3,4,5-TRIMETHOXYBENZYL)PYRIMIDINE-2,4-DIYLAMINE
  • 2,4-DIAMINO-5-(3,4,5-TRIMETHOXYBENZYL)PYRIMIDE
  • 2,4-DIAMINO-5-(3',4',5'-TRIMETHOXYBENZYL)PYRIMIDINE
  • 2,4-DIAMINO-5-(3,4,5-TRIMETHOXYBENZYL)PYRIMIDINE
  • High quality Trimethoprim cas 738-70-5 CAS NO.738-70-5
  • Trimethoprim in stock GMP Factory
  • 5-(3,4,5-Trimethoxy-benzyl)-pyrimidine-2,4-diamine
  • Baktar
  • ST mixture
  • Sulfamethoxazole/trimetoprim
  • Trimetoprim/sulfamethoxazole
  • Trimetoprim/sulfamethoxazole,(1:x)
  • 2,4,6-Triisopropylthiophenol
  • [2-amino-5-(3,4,5-trimethoxybenzyl)pyrimidin-4-yl]amine
  • Trimethoprin(TMP)
  • Trimethoprim,2,4-Diamino-5-(3,4,5-trimethoxybenzyl)pyrimidine
  • Trimethoprim (300 mg)
  • Trimethoprim 99.8%
  • TRIMETHOPRIMRESEARCH GRADE
  • TRIMETHOPRIMMICRONIZED
  • 5-[(3,4,5-TriMethoxyphenyl)Methyl]-
  • TriMethopriM COS
  • TriMethopriM 0
  • TMP (triMethopriM)
  • Trimethoprim solution,1000ppm
  • Trimethoprim Solution, 100ppm
  • TRIMETOPRIM
  • TRIMETHOPRIM
  • TRIMETHORPIM
  • 2,4-diamino-5-(3,4,5-trimethoxybenzyl)-pyrimidin
  • 2,4-Pyrimidinediamine, 5-[(3,4,5-trimethoxyphenyl)methyl]-
  • 5-((3,4,5-trimethoxyphenyl)-methyl)-4-pyrimidinediamine
  • 5-(3,4,5-Trimethoxybenzyl)-2,4-pyrimidinediamine
  • Bactramin
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