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

基本信息

化学结构

分子式

C₁₄H₁₈N₄O₃

分子量

290.31772

精确质量

290.13789046

电荷

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

计算属性

JChem

LogD (pH = 7.4)

1.10

LogD (pH = 5.5)

0.02

Log P

1.28

可自由旋转的化学键

质子供体

质子受体

里宾斯基五规则

true

Acid pKa

7.16

极化表面积

105.51

极化性

29.71

摩尔折射率

81.51

LOG S

-2.80

数据来源

名称和标识

别名

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)pyrimidineTrimanylUretrimProloprim5-[(3,4,5-Trimethoxyphenyl)methyl]-2,4-pyrimidinediamineInstalacMonotrimWellcoprim2,4-Diamino-5-(3',4',5'-trimethoxybenzyl)pyrimidineSyraprimTiempeTrimpex2,4-diamino-5-(3,4,5-trimethoxybenzyl)pyrimidineTrimethoprim5-[(3,4,5-trimethoxyphenyl)methyl]-2,4-pyrimidinediaminetrimethoprimTRIMETHOPRIMTrimpexProloprim

IUPAC标准名

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

IUPAC传统名

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

商标名

TrimexazoleGantaprimSeptraBactrim DSTrimopanSulprimMethoprimPrimoseptTrimethopriomAlprimBaktarUnitrimTrimanylSulmeprimSyraprimMonotrimAbacinSuprimSulfamethoprimGantrimCo-TrimoxazoleIpralSulfamethoprim-DSMicrotrimSeptrinSupracombinUroplusBactinChemotrimMonotriminTrigonylTrimesulfSulfatrimFectrimTriprimComox

API名称

Trimethoprim

名称和标识

数据登录号

化合物性质

分子相关蛋白质

分子图谱

暂无数据

点击上传数据

描述信息

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
Primarily used as an antibacterial agent. Dihydrofolate reductase inhibitor with selectivity for the prokaryote enzyme.
欧洲委员会 (EU) 2009 年 12 月 22 日第 37/2010 号关于动物源食品药理活性物质及其最大残留限值分类的规定。
Other Notes
Specific inhibitor of formulation. Widely used in studies on dihydrofolate reductase1,2.
法律信息
VETRANAL 商标 Sigma-Aldrich Co. LLC

92131

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.

描述信息

参考文献

PubChem文献

数据源提供

• 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).

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

参考文献

生物活性

PubChem BioAssay

生物活性

参考文献

PubChem文献

数据源提供

• 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).

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

生物活性

PubChem BioAssay

化合物性质

描述信息

DrugBank

DB00440

Drug Groups

approved

Description

Indication

Pharmacology

Toxicity

LD₅₀=4850 (orally in mice)

Affected Organisms

Gram negative and gram positive bacteria

Biotransformation

Hepatic metabolism to oxide and hydroxylated metabolites.

Absorption

Half Life

8-11 hours in adults with normal renal function

Protein Binding

42-46% bound to plasma proteins

Elimination

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]

• 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

02718