Trimethoprim

Base Information

• Chemical Name: Trimethoprim
• CAS No.: 738-70-5
• Molecular Formula: C14H18N4O3
• Molecular Weight: 290.322
• Hs Code.: 29335995
• European Community (EC) Number: 212-006-2
• NSC Number: 757370,752719,106568
• UN Number: 2811
• UNII: AN164J8Y0X
• DSSTox Substance ID: DTXSID3023712
• Nikkaji Number: J9.454D
• Wikipedia: Trimethoprim
• Wikidata: Q422665
• NCI Thesaurus Code: C908
• RXCUI: 10829
• Pharos Ligand ID: 1UYSPXCG15AL
• Metabolomics Workbench ID: 42795
• ChEMBL ID: CHEMBL22
• Mol file: 738-70-5.mol

Synonyms:Bacidal;Sulthrim;Bactrim;Resprim Forte;Trimetoprim [DCIT];Deprim;5-(3,4,5-Trimethoxybenzyl)-2,4-diaminopyrimidine;Briscotrim;Salvatrim;Metoprim;Bacdan;Abaprim;Bencole;Bacticel;Trimez-IFSA;Trimethopim(TMP);Sulfamethoxazole Trimethoprim;Bethaprim;Trimexol;Sulfamethoprim;Streptoplus;Trimethoprim [USAN:BAN:INN:JAN];5-[(3,4,5-trimethoxyphenyl)methyl]pyrimidine-2,4-diamine;Tmp Smx;Trimethoprime [INN-French];NIH 204;Wellcoprin;Roubal;Trimpex (TN);Co-Trimoxizole;Trimetoprima [INN-Spanish];Syraprim;Monotrimin;Protrin;2,4-Diamino-5-(3,4,5-trimethoxybenzyl)pyrimidine;

Chemical Property of Trimethoprim

Chemical Property:

• Appearance/Colour: Odorless white powder.
• Melting Point: 199-203 °C
• Refractive Index: 1.6000 (estimate)
• Boiling Point: 525.956 °C at 760 mmHg
• PKA: 6.6(at 25℃)
• Flash Point: 271.889 °C
• PSA: 105.51000
• Density: 1.252 g/cm³
• LogP: 2.42000
• Storage Temp.: 2-8°C
• Solubility.: DMSO: soluble
• Water Solubility.: <0.1 g/100 mL at 24℃
• XLogP3: 0.9
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 7
• Rotatable Bond Count: 5
• Exact Mass: 290.13789045
• Heavy Atom Count: 21
• Complexity: 307
• Transport DOT Label: Poison

Purity/Quality:

99%, ^*data from raw suppliers

Trimethoprim ^*data from reagent suppliers

Safty Information:

• Pictogram(s): T
• Hazard Codes: T
• Statements: 25
• Safety Statements: 45-24/25

MSDS Files:

SDS file from LookChem

Total 1 MSDS from other Authors

Useful:

• Canonical SMILES: COC1=CC(=CC(=C1OC)OC)CC2=CN=C(N=C2N)N
• Recent ClinicalTrials: The Effect of SLC19A3 Inhibition on the Pharmacokinetics of Thiamine
• Recent EU Clinical Trials: 3-day intravenous antibiotic treatment versus 3-day intravenous followed by 7-day oral antibiotic treatment for acute pyelonephritis in children 1 month to 3 years old: a non-inferiority open randomized multicentric clinical trial
• Recent NIPH Clinical Trials: Drug-drug interaction study of repaglinide with regard to CYP2C8 and OATP1B1
• Uses: 1. It can be used as a synergistic antimicrobial drugs; it can also be used for treating bacterial infections and coccidiosis in poultry. 2. It is a novel orally administrated broad-spectrum antibiotics. It has a similar antibacterial spectrum with sulfa drugs but with a stronger potency. It is effective in treating a variety of Gram positive and negative bacteria. Since the bacteria is easy to evolve drug resistance to this product, it is not suitable to be used alone as an antimicrobial drug. The combination between trimethoprim and sulfa drugs can enhance the antibacterial activity by several times to several dozens of times. The product is mainly used for being as the synergistic drugs for sulfonamide drugs with a general ratio of 1: 5 for usage. It can also be used as a veterinary drug for treatment of avian sepsis caused by Escherichia coli, salmonellosis, fowl typhoid, cholera, and respiratory system secondary bacterial infections. It can also be used for the treatment of coccidiosis. 3. Application: used as antibacterial synergistic drugs; treat respiratory tract infections, urinary tract infections and intestinal infections when being used alone. The above information is edited by the lookchem of Dai xiongfeng. An antibacterial and inhibitor of formylation. Dihydrofolate reductase inhibitor with selectivity for the prokaryote enzyme.Trimethoprim is an antibiotic involved in the treatment of urinary tract infections, middle ear infections and traveler?s diarrhea. It is associated with sulfamethoxazole and interferes with the cellular metabolism of folic acid in the bacterial cell by blocking the biosynthesis of nucleotides. Furthermore, It is also used to treat and prevent Pneumocystis jiroveci pneumonia. anti-inflammatory An antibacterial agent which selectively inhibits dihydrofolate reductase.
• Description: 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.
• 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.
• Drug interactions: Potentially hazardous interactions with other drugs Anti-arrhythmics: increased risk of ventricular arrhythmias with amiodarone - avoid; concentration of procainamide increased. Antiepileptics: antifolate effect and concentration of fosphenytoin and phenytoin increased. Antimalarials: increased risk of antifolate effect with pyrimethamine. Ciclosporin: increased risk of nephrotoxicity; concentration of ciclosporin reduced by IV trimethoprim. Cytotoxics: increased risk of haematological toxicity with azathioprine, methotrexate and mercaptopurine; antifolate effect of methotrexate increased. Tacrolimus: possible increased risk of nephrotoxicity.

Technology Process of Trimethoprim

There total 39 articles about Trimethoprim which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 95.0%

3-anilino-2-(3,4,5-trimethoxybenzyl)propenenitrile (30078-48-9) + guanidine nitrate (506-93-4) → 5-(3,4,5-trimethoxybenzyl)pyrimidine-2,4-diamine (738-70-5)

Guidance literature:

guanidine nitrate; With sodium methylate; at 30 ℃; for 0.5h; Reflux;

3-anilino-2-(3,4,5-trimethoxybenzyl)propenenitrile; for 10h; Reflux;

DOI:10.1080/00397911.2011.644380

Reference yield: 90.0%

β-(p-methylanilino)-β-3,4,5-trimethoxybenzylacrylonitrile → 5-(3,4,5-trimethoxybenzyl)pyrimidine-2,4-diamine (738-70-5)

Guidance literature:

Reference yield: 85.0%

2,4-dichloro-5-(3,4,5-trimethoxybenzyl)pyrimidine (55694-05-8) → 5-(3,4,5-trimethoxybenzyl)pyrimidine-2,4-diamine (738-70-5)

Guidance literature:

With ammonia; In methanol; at 175 ℃; for 6h;

DOI:10.1021/ol0616790

upstream raw materials:

3,4,5-trimethoxy-2'-(methoxymethyl)cinnamonitrile

sodium methylate

diguanidine carbonate

guanidine hydrochloride

Downstream raw materials:

C₁₉H₁₀Br₄O₅S*C₁₄H₁₈N₄O₃

N-[4-(2,2-dimethyl-propionylamino)-5-(2-iodo-3,4,5-trimethoxy-benzyl)-pyrimidin-2-yl]-2,2-dimethyl-propionamide

2,4-diamino-5-(3,4,5-trimethoxybenzoyl)pyrimidine

2-amino-4-hydroxy-5-(3,4,5-trimethoxybenzyl)pyrimidine

Refernces

• 1、 -. "METHODS AND COMPOSITIONS FOR OPTOCHEMICAL CONTROL OF CRISPR-CAS9". Paragraph 0044. . Retrieved 2021/10/15.
• 2、 -. "Synthetic method of trimethoprim". . . Retrieved 2016/10/08.