CAS 738-70-5|2,4-Diamino-5-[3,4,5-trimethoxy-benzyl]pyrimidine|Trimethoprim|5-[(3,4,5-trimethoxyphenyl)methyl]pyrimidine-2,4-diamine|trimethoprim|5-(3,4,5-Trimethoxybenzyl)-2,4-pyrimidinediamine|Tri...

General Information

Structure

Molecular Formula

C₁₄H₁₈N₄O₃

Molecular Mass

290.31772

Exact Mass

290.13789046

Charge

InChI

InChI=1S/C14H18N4O3/c1-19-10-5-8(6-11(20-2)12(10)21-3)4-9-7-17-14(16)18-13(9)15/h5-7H,4H2,1-3H3,(H4,15,16,17,18)

InChIKey

IEDVJHCEMCRBQM-UHFFFAOYSA-N

Canonic Smiles

COc1cc(Cc2cnc(nc2N)N)cc(c1OC)OC

Isomeric Smiles

O(c1cc(Cc2c(nc(nc2)N)N)cc(OC)c1OC)C

Calculated Properties

JChem

LogD (pH = 7.4)

1.10

LogD (pH = 5.5)

0.02

Log P

1.28

Rotatable Bonds

H Donor

H Acceptors

Lipinski's Rule of Five

true

Acid pKa

7.16

Polar Surface Area

105.51

Polarizability

29.71

Molar Refractivity

81.51

LOG S

-2.80

Data Source

Names and Identifiers

IUPAC name

5-[(3,4,5-trimethoxyphenyl)methyl]pyrimidine-2,4-diamine

IUPAC Traditional name

trimethoprim 5-[(3,4,5-trimethoxyphenyl)methyl]pyrimidine-2,4-diamine

Synonyms

2,4-Diamino-5-[3,4,5-trimethoxy-benzyl]pyrimidineTrimethoprim5-(3,4,5-Trimethoxybenzyl)-2,4-pyrimidinediamineTrimethoprim2,4-二氨基-5-(3,4,5-三甲氧基苄基)嘧啶甲氧苄啶5-(3,4,5-trimethoxybenzyl)pyrimidine-2,4-diamine2,4-Diamino-5-(3,4,5-trimethoxybenzyl)pyrimidine5-[(3,4,5-Trimethoxyphenyl)methyl]-2,4-pyrimidinediamineTrimanylSyraprimMonotrimUretrimWellcoprim2,4-Diamino-5-(3',4',5'-trimethoxybenzyl)pyrimidineTiempeInstalacProloprimTrimpex2,4-diamino-5-(3,4,5-trimethoxybenzyl)pyrimidineTrimethoprimtrimethoprim5-[(3,4,5-trimethoxyphenyl)methyl]-2,4-pyrimidinediamineTRIMETHOPRIMProloprimTrimpex

Brand Name

TrimopanSulfamethoprim-DSSulmeprimSuprimUroplusSulprimTrimexazoleCo-TrimoxazoleMonotrimGantrimMethoprimPrimoseptBaktarAbacinTrimanylAlprimUnitrimSeptrinSupracombinSyraprimBactrim DSSulfamethoprimSeptraIpralGantaprimTrimethopriomMicrotrimTmp-RatiopharmLidaprimWellcoprimUro-SeptraPriloprimOraprimBactraminComoxTrimetoprimUroplus SSTrimogalSulfamethoxazole & TrimethoprimKepinolBactinTrimesulfMonotriminFectrimTrigonylIdotrimChemotrimSulfatrimSulfatrim PediatricSulfatrim-DSTeleprimTriprimSeptra GrapeAbaprimTrimpex 200Trimeth/SulfaInstalacImeximTrimpexUroplus DSProloprimSeptra DSSulfatrim-SSNopilTiempeThiocuranBactrim PediatricDrylinEusaprimUretrimCotrim D.S.CotrimTrimethioprimSumetrolimLaratrimMonoprimSulmeprim PediatricSulfotrimApo-SulfatrimBactrimPrimsolSigaprim

API Name

Trimethoprim

Names and Identifiers

Registration numbers

Properties

Related Proteins

Molecular Spectra

No Data Available

Click here to submit data

Molecule Details

DrugBank

DB00440

Drug Groups

approved

Description

A pyrimidine inhibitor of dihydrofolate reductase, it is an antibacterial related to pyrimethamine. The interference with folic acid metabolism may cause a depression of hematopoiesis. It is potentiated by sulfonamides and the trimethoprim-sulfamethoxazole combination is the form most often used. It is sometimes used alone as an antimalarial. Trimethoprim resistance has been reported. [PubChem]

Indication

For the treatment of urinary tract infections, uncomplicated pyelonephritis (with sulfamethoxazole) and mild acute prostatitis. May be used as pericoital (with sulfamethoxazole) or continuous prophylaxis in females with recurrent cystitis. May be used as an alternative to treat asymptomatic bacteriuria during pregnancy (only before the last 6 weeks of pregnancy). Other uses include: alternative agent in respiratory tract infections (otitis, sinusitus, bronchitis and pneumonia), treatment of Pneumocystis jirovecii pneumonia (acute or prophylaxis), Nocardia infections, and traveller's diarrhea.

Pharmacology

Trimethoprim is a pyrimidine analogue that disrupts folate synthesis, an essential part of the thymidine synthesis pathway. Inhibition of the enzyme starves the bacteria of nucleotides necessary for DNA replication.The drug, therefore, exhibits bactericidal activity.

Toxicity

LD₅₀=4850 (orally in mice)

Affected Organisms

Gram negative and gram positive bacteria

Biotransformation

Hepatic metabolism to oxide and hydroxylated metabolites.

Absorption

Readily and almost completely absorbed in the GI tract with peak serum concentrations attained 1-4 hours after oral administration. Widely distributed to tissues and fluids including kidney, lung, seminal fluid, aqueous humour, middle ear fluid, sputum, vaginal secretions, bile, bone and CSF.

Half Life

8-11 hours in adults with normal renal function

Protein Binding

42-46% bound to plasma proteins

Elimination

Ten to twenty percent of trimethoprim is metabolized, primarily in the liver; the remainder is excreted unchanged in the urine.
After oral administration, 50% to 60% of trimethoprim is excreted in the urine within 24 hours, approximately 80% of this being unmetabolized trimethoprim. Trimethoprim also passes the placental barrier and is excreted in human milk.

References

• Brumfitt W, Hamilton-Miller JM: Reassessment of the rationale for the combinations of sulphonamides with diaminopyrimidines. J Chemother. 1993 Dec;5(6):465-9. [Pubmed]

• Brumfitt W, Hamilton-Miller JM: Limitations of and indications for the use of co-trimoxazole. J Chemother. 1994 Feb;6(1):3-11. [Pubmed]

• Bean DC, Livermore DM, Papa I, Hall LM: Resistance among Escherichia coli to sulphonamides and other antimicrobials now little used in man. J Antimicrob Chemother. 2005 Nov;56(5):962-4. Epub 2005 Sep 8. [Pubmed]

• Felmingham D, Reinert RR, Hirakata Y, Rodloff A: Increasing prevalence of antimicrobial resistance among isolates of Streptococcus pneumoniae from the PROTEKT surveillance study, and compatative in vitro activity of the ketolide, telithromycin. J Antimicrob Chemother. 2002 Sep;50 Suppl S1:25-37. [Pubmed]

• Johnson JR, Manges AR, O'Bryan TT, Riley LW: A disseminated multidrug-resistant clonal group of uropathogenic Escherichia coli in pyelonephritis. Lancet. 2002 Jun 29;359(9325):2249-51. [Pubmed]

External Links

• [Wikipedia]

• [RxList]

• [Drugs.com]

MP Biomedicals

02195527

Crystalline
A specific inhibitor of formylation.

Wikipedia

Trimethoprim

Sigma Aldrich

T7883

Application
Primarily used as an antibacterial agent. Dihydrofolate reductase inhibitor with selectivity for the prokaryote enzyme.
Trimethoprim is primarily used as an antibacterial agent. It has dihydrofolate reductase inhibitor activity with selectivity for the prokaryote enzyme. It is used to treat urinary tract infections, mild acute prostatitis, recurrent cystitis, asymptomatic bacteriuria during pregnancy and respiratory tract infections1.
Other Notes
Specific inhibitor of formulation. Widely used in studies on dihydrofolate reductase2,3.
Biochem/physiol Actions
The combination of trimethoprim and sulfamethoxazole interferes with the cellular metabolism of folic acid in the bacterial cell by blocking the biosynthesis of nucleotides. Trimethoprim binds to dihydrofolate reductase and inhibits the reduction of dihydrofolic acid (DHF) to tetrahydrofolic acid (THF). THF is an essential precursor in the thymidine synthesis pathway and interference with this pathway inhibits bacterial DNA synthesis1.
Protocols & Applications
Antibiotic Selector for application, solubility, solution stability, working concentration, and mode of action information

02718

Application
Primarily used as an antibacterial agent. Dihydrofolate reductase inhibitor with selectivity for the prokaryote enzyme.
Other Notes
Specific inhibitor of formulation. Widely used in studies on dihydrofolate reductase1,2.

46984

Application
Commission Regulation (EU) No 37/2010 of 22 December 2009 on pharmacologically active substances and their classification regarding maximum residue limits in foodstuffs of animal origin
Primarily used as an antibacterial agent. Dihydrofolate reductase inhibitor with selectivity for the prokaryote enzyme.
Other Notes
Specific inhibitor of formulation. Widely used in studies on dihydrofolate reductase1,2.
Legal Information
VETRANAL is a trademark of Sigma-Aldrich Co. LLC

TRC

T795615

Antibacterial.

ChEBI

CHEBI:45924

An aminopyrimidine antibiotic whose structure consists of pyrimidine 2,4-diamine and 1,2,3-trimethoxybenzene moieties linked by a methylene bridge.

Molecule Details

References

PubChem Literature

From Data Sources

• Johnson JR, Manges AR, O'Bryan TT, Riley LW: A disseminated multidrug-resistant clonal group of uropathogenic Escherichia coli in pyelonephritis. Lancet. 2002 Jun 29;359(9325):2249-51. Pubmed

• Brumfitt W, Hamilton-Miller JM: Reassessment of the rationale for the combinations of sulphonamides with diaminopyrimidines. J Chemother. 1993 Dec;5(6):465-9. Pubmed

• Brumfitt W, Hamilton-Miller JM: Limitations of and indications for the use of co-trimoxazole. J Chemother. 1994 Feb;6(1):3-11. Pubmed

• Mol. Pharmacol., 1: 126, (1965).

• Brogden, R.N., et al.: Drugs, 23, 405 (1978)

• Manius, G.J., et al.: Anal. Profiles Drug Subs., 7, 445 (1978)

• Roth, B., et al.: J. Med. Chem., 23, 379 (1978)

• Brossi, A. et al., J. Med. Chem., 1971, 14, 462, (synth)

• Burchall, J.J., Antibiotics (N.Y.), 1975, 3, 304, (rev)

• Negwer, M., Organic-Chemical Drugs and their Synonyms, 7th edn., Akademie-Verlag, 1994, 4092

• Lewis, R.J., Sax's Dangerous Properties of Industrial Materials, 8th edn., Van Nostrand Reinhold, 1992, TKX000; TKZ000

• Sigel, C.W., Handb. Exp. Pharmacol., 1983, 64, 163, (rev, metab)

• Roth, B. et al., J. Med. Chem., 1980, 23, 379; 535, (synth)

• Huovinen, P., Antimicrob. Agents Chemother., 1987, 31, 1451, (rev, props)

• Martindale, The Extra Pharmacopoeia, 30th edn., Pharmaceutical Press, 1993, 219

• Brogden, R.N. et al., Drugs, 1982, 23, 405, (rev, pharmacol)

• Koetzle, T.F. et al., J.A.C.S., 1976, 98, 2074, (cryst struct)

• Manius, G.J., Anal. Profiles Drug Subst., 1978, 7, 445, (rev, synth, props, anal)

• Bryan, R.F. et al., Acta Cryst. C, 1987, 43, 2412, (cryst struct)

References

Bioactivity

PubChem BioAssay

Bioactivity