Compounds > metioprim
Page last updated: 2024-11-06

metioprim

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth

Metioprim is a synthetic antimicrobial agent belonging to the diaminopyrimidine class. It inhibits the enzyme dihydrofolate reductase, which is essential for the synthesis of tetrahydrofolic acid, a cofactor required for purine and thymidylate biosynthesis. This inhibition ultimately leads to the disruption of DNA synthesis and cell growth. Metioprim is particularly effective against protozoa such as *Toxoplasma gondii* and *Pneumocystis jirovecii*, and is often used in combination with sulfamethoxazole, forming the widely used antibiotic co-trimoxazole (also known as Bactrim or Septra). Metioprim is also used to treat bacterial infections, particularly urinary tract infections, and is under investigation for its potential use in treating cancer.'

Cross-References

ID SourceID
PubMed CID68590
CHEMBL ID56318
SCHEMBL ID193012
MeSH IDM0110607

Synonyms (37)

Synonym
ro 126995
he 909
2,4-pyrimidinediamine, 5-((3,5-dimethoxy-4-(methylthio)phenyl)methyl)-
methioprim (bacteriostat)
ro 12-6995
metioprimum [inn-latin]
5-((3,5-dimethoxy-4-(methylthio)phenyl)methyl)-2,4-pyrimidinediamine
metioprima [inn-spanish]
2,4-diamino-5-(3,5-dimethoxy-4-(methylthio)benzyl)pyrimidine
metioprim
metioprime [inn-french]
2,4-diamino-5-(3,5-dimethoxy-4-methylthiobenzyl)pyrimidine
5-[(3,5-dimethoxy-4-methylsulfanyl-phenyl)methyl]pyrimidine-2,4-diamine
metioprim (usan/inn)
D05005
68902-57-8
ro-12-6995
CHEMBL56318
5-[(3,5-dimethoxy-4-methylsulfanylphenyl)methyl]pyrimidine-2,4-diamine
metioprim [usan:inn:ban]
metioprima
metioprimum
unii-k29kwu39j0
metioprime
k29kwu39j0 ,
bdbm50405997
2,4-pyrimidinediamine,5-[[3,5-dimethoxy-4-(methylthio)phenyl]methyl]-
metioprim [inn]
metioprim [usan]
metioprim [mart.]
2,4-diamino-5-[3,5-dimethoxy-4-(methylthio)benzyl]pyrimidine
SCHEMBL193012
DTXSID60218982
Q27281845
HY-122289
CS-0083400
AKOS040746107

Research Excerpts

Pharmacokinetics

ExcerptReferenceRelevance
" The elimination half-life was much shorter in goats (23 +/- 4 min."( Pharmacokinetics and metabolism of metioprim in pigs and goats.
Gyrd-Hansen, N; Nielsen, P; Olsen, CE; Xia, WJ, 1987)		0.55
" The pharmacokinetic parameters of unchanged metioprim were derived by analyzing plasma level curves using a two-compartment model."( Pharmacokinetics of metioprim in normal subjects and patients with impaired renal function.
Bishop-Freudling, GB; Kaiser, W; Köhler, M; Reutter, FW; Strobel, K; Vergin, H, 1983)		0.85

Compound-Compound Interactions

The activities of the 2,4-diamino-5-benzylpyrimidines brodimoprim and metioprim against anaerobic bacteria were tested alone and in combination with sulfonamides.

ExcerptReferenceRelevance
"Bacterial growth kinetics and checkerboard titration experiments have been performed to determine the inhibitory power of metioprim (I) and brodimoprim (II) alone and in combination with diaminodiphenylsulfone (DDS) using Escherichia coli and mycobacteria as test organisms."( Bacterial growth kinetics of Escherichia coli and mycobacteria in the presence of brodimoprim and metioprim alone and in combination with sulfamerazine and dapsone (VI).
Rosenfeld, M; Seydel, JK; Wempe, EG, 1983)		0.69
"The activities of the 2,4-diamino-5-benzylpyrimidines brodimoprim and metioprim against anaerobic bacteria were tested alone and in combination with sulfonamides."( Activity of brodimoprim and metioprim alone and in combination with sulfonamides against anaerobic bacteria.
Schwarzenbach, J; Wüst, J, 1983)		0.79

Bioavailability

ExcerptReferenceRelevance
" In dogs with healthy meninges, the CSF bioavailability - expressed as the ratio of CSF/plasma area under the curve 0-5-hour values - following continuous infusion was determined to be 86."( Diffusion of metioprim, tetroxoprim and sulphadiazine in the cerebrospinal fluid of dogs with healthy meninges and dogs with experimental meningitis.
Armengaud, H; Bishop-Freudling, GB; Foing, N; Szelenyi, I; van Tho, T; Vergin, H, 1984)		0.64
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Protein Targets (3)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Dihydrofolate reductaseGallus gallus (chicken)Ki51.28610.11220.21580.3311AID56467
Dihydrofolate reductaseLacticaseibacillus caseiKi0.05620.00001.26756.3096AID57779
Dihydrofolate reductase Salmonella enterica subsp. enterica serovar TyphiKi0.00850.00450.11790.6607AID57579
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (6)

Processvia Protein(s)Taxonomy
one-carbon metabolic processDihydrofolate reductaseGallus gallus (chicken)
response to methotrexateDihydrofolate reductaseGallus gallus (chicken)
tetrahydrofolate metabolic processDihydrofolate reductaseGallus gallus (chicken)
tetrahydrofolate biosynthetic processDihydrofolate reductaseGallus gallus (chicken)
dihydrofolate metabolic processDihydrofolate reductaseGallus gallus (chicken)
folic acid metabolic processDihydrofolate reductaseGallus gallus (chicken)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (3)

Processvia Protein(s)Taxonomy
mRNA bindingDihydrofolate reductaseGallus gallus (chicken)
dihydrofolate reductase activityDihydrofolate reductaseGallus gallus (chicken)
NADP bindingDihydrofolate reductaseGallus gallus (chicken)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (1)

Processvia Protein(s)Taxonomy
mitochondrionDihydrofolate reductaseGallus gallus (chicken)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (10)

Assay IDTitleYearJournalArticle
AID57574Activity against dihydrofolate reductase of Escherichia coli strain MB 14281992Journal of medicinal chemistry, Aug-21, Volume: 35, Issue:17
Application of neural networks: quantitative structure-activity relationships of the derivatives of 2,4-diamino-5-(substituted-benzyl)pyrimidines as DHFR inhibitors.
AID27589Partition coefficient (logD) (0.01 N NaOH)1989Journal of medicinal chemistry, Aug, Volume: 32, Issue:8
On the structure selectivity problem in drug design. A comparative study of benzylpyrimidine inhibition of vertebrate and bacterial dihydrofolate reductase via molecular graphics and quantitative structure-activity relationships.
AID57779Inhibitory activity against Lactobacillus casei dihydrofolate reductase1989Journal of medicinal chemistry, Aug, Volume: 32, Issue:8
On the structure selectivity problem in drug design. A comparative study of benzylpyrimidine inhibition of vertebrate and bacterial dihydrofolate reductase via molecular graphics and quantitative structure-activity relationships.
AID65359Inhibition of growth of methotrexate-resistant (MB1428) strain of Escherichia coli cells.1985Journal of medicinal chemistry, Dec, Volume: 28, Issue:12
Quantitative structure-activity relationship of antifolate inhibition of bacteria cell cultures resistant and sensitive to methotrexate.
AID57083Inhibitory activity against dihydrofolate reductase2001Journal of medicinal chemistry, Aug-16, Volume: 44, Issue:17
Adaptive neuro-fuzzy inference system: an instant and architecture-free predictor for improved QSAR studies.
AID65357Inhibition of growth of methotrexate-sensitive (MB1417) strain of Escherichia coli cells.1985Journal of medicinal chemistry, Dec, Volume: 28, Issue:12
Quantitative structure-activity relationship of antifolate inhibition of bacteria cell cultures resistant and sensitive to methotrexate.
AID57579Inhibitory activity against Escherichia coli dihydrofolate reductase1991Journal of medicinal chemistry, Jan, Volume: 34, Issue:1
On the optimization of hydrophobic and hydrophilic substituent interactions of 2,4-diamino-5-(substituted-benzyl)pyrimidines with dihydrofolate reductase.
AID56461Inhibition of chicken liver dihydrofolate reductase1986Journal of medicinal chemistry, May, Volume: 29, Issue:5
Inhibition of chicken liver dihydrofolate reductase by 5-(substituted benzyl)-2,4-diaminopyrimidines. A quantitative structure-activity relationship and graphics analysis.
AID56467Inhibitory activity against chicken liver dihydrofolate reductase1989Journal of medicinal chemistry, Aug, Volume: 32, Issue:8
On the structure selectivity problem in drug design. A comparative study of benzylpyrimidine inhibition of vertebrate and bacterial dihydrofolate reductase via molecular graphics and quantitative structure-activity relationships.
AID23497Partition coefficient (logD) (aqueous phase 0.1 N HCl)1986Journal of medicinal chemistry, May, Volume: 29, Issue:5
Inhibition of chicken liver dihydrofolate reductase by 5-(substituted benzyl)-2,4-diaminopyrimidines. A quantitative structure-activity relationship and graphics analysis.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (16)

TimeframeStudies, This Drug (%)All Drugs %
pre-199013 (81.25)18.7374
1990's2 (12.50)18.2507
2000's1 (6.25)29.6817
2010's0 (0.00)24.3611
2020's0 (0.00)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials0 (0.00%)5.53%
Reviews0 (0.00%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other17 (100.00%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]
SubstanceRelationship StrengthStudiesTrialsClassesRoles
dapsone
[no description available]		6.9610substituted aniline;
sulfone		anti-inflammatory drug;
antiinfective agent;
antimalarial;
leprostatic drug
pyrimethamine
Maloprim: contains above 2 cpds		1.9610aminopyrimidine;
monochlorobenzenes		antimalarial;
antiprotozoal drug;
EC 1.5.1.3 (dihydrofolate reductase) inhibitor
sulfadiazine
Sulfadiazine: One of the short-acting SULFONAMIDES used in combination with PYRIMETHAMINE to treat toxoplasmosis in patients with acquired immunodeficiency syndrome and in newborns with congenital infections.. sulfadiazine : A sulfonamide consisting of pyrimidine with a 4-aminobenzenesulfonamido group at the 2-position.. diazine : The parent structure of the diazines.		1.9610pyrimidines;
substituted aniline;
sulfonamide antibiotic;
sulfonamide		antiinfective agent;
antimicrobial agent;
antiprotozoal drug;
coccidiostat;
drug allergen;
EC 1.1.1.153 [sepiapterin reductase (L-erythro-7,8-dihydrobiopterin forming)] inhibitor;
EC 2.5.1.15 (dihydropteroate synthase) inhibitor;
environmental contaminant;
xenobiotic
sulfamerazine
[no description available]		6.9610pyrimidines;
sulfonamide antibiotic;
sulfonamide		antiinfective agent;
drug allergen
trimethoprim
Trimethoprim: A pyrimidine inhibitor of dihydrofolate reductase, it is an antibacterial related to PYRIMETHAMINE. It is potentiated by SULFONAMIDES and the TRIMETHOPRIM, SULFAMETHOXAZOLE DRUG COMBINATION is the form most often used. It is sometimes used alone as an antimalarial. TRIMETHOPRIM RESISTANCE has been reported.. trimethoprim : An aminopyrimidine antibiotic whose structure consists of pyrimidine 2,4-diamine and 1,2,3-trimethoxybenzene moieties linked by a methylene bridge.		9.1160aminopyrimidine;
methoxybenzenes		antibacterial drug;
diuretic;
drug allergen;
EC 1.5.1.3 (dihydrofolate reductase) inhibitor;
environmental contaminant;
xenobiotic
cycloguanil
cycloguanil: the active metabolite of proguanil; antifolate drug; structure in first source. cycloguanil : A triazine in which a 1,6-dihydro-1,3,5-triazine ring is substituted at N-1 by a 4-chlorophenyl group, at C-2 and -4 by amino groups and at C-6 by gem-dimethyl groups. A dihydrofolate reductase inhibitor, it is a metabolite of the antimalarial drug proguanil.		1.9610triazinesantifolate;
antiinfective agent;
antimalarial;
antiparasitic agent;
antiprotozoal drug;
EC 1.5.1.3 (dihydrofolate reductase) inhibitor
4,6-diamino-2,2-dimethyl-1,2-dihydro-1-phenyl-s-triazine
4,6-diamino-2,2-dimethyl-1,2-dihydro-1-phenyl-s-triazine: structure in first source		1.9610
diaveridine
diaveridine: RN given refers to parent cpd; structure. diaveridine : An aminopyrimidine in which the pyrimidine ring carries amino substituents at C-2 and C-4 and a 3,4-dimethoxybenzyl group at C-5. A folic acid antagonist, it is used as a synergist with sulfonamides against the parasitic Eimeria species.		3.2360aminopyrimidineantiparasitic agent;
drug allergen
metoprine
metoprine: histamine methyltransferase antagonist		1.9610
piritrexim
piritrexim: RN given refers to parent cpd; structure given in first source		1.9610
tetroxoprim
tetroxoprim: structure given in Negwer 5th ed, #6419		3.67100dimethoxybenzene
aditoprim
aditoprim: structure given in first source		2.8940
brodimoprim
brodimoprim: inhibits dihydrofolate reductase. brodimoprim : An aminopyrimidine that is 2,4-diaminopyrimidine in which the hydrogen at position 5 has been replaced by a 4-bromo-3,5-dimethoxybenzyl group.		3.5890aminopyrimidine;
bromobenzenes;
methoxybenzenes		antibacterial drug;
antiinfective agent;
EC 1.5.1.3 (dihydrofolate reductase) inhibitor
epiroprim
epiroprim: an analog of trimethoprim with improved antimicrobial and pharmacokinetic properties; structure given in first source		3.0750
2,4-diamino-5-benzylpyrimidine
2,4-diamino-5-benzylpyrimidine: structure given in first source		3.2360
methotrexate
[no description available]		1.9610dicarboxylic acid;
monocarboxylic acid amide;
pteridines		abortifacient;
antimetabolite;
antineoplastic agent;
antirheumatic drug;
dermatologic drug;
DNA synthesis inhibitor;
EC 1.5.1.3 (dihydrofolate reductase) inhibitor;
immunosuppressive agent
ConditionIndicatedRelationship StrengthStudiesTrials
Pachymeningitis
[description not available]		01.9610
Infections, Staphylococcal
[description not available]		01.9610
Meningitis
Inflammation of the coverings of the brain and/or spinal cord, which consist of the PIA MATER; ARACHNOID; and DURA MATER. Infections (viral, bacterial, and fungal) are the most common causes of this condition, but subarachnoid hemorrhage (HEMORRHAGES, SUBARACHNOID), chemical irritation (chemical MENINGITIS), granulomatous conditions, neoplastic conditions (CARCINOMATOUS MENINGITIS), and other inflammatory conditions may produce this syndrome. (From Joynt, Clinical Neurology, 1994, Ch24, p6)		06.9610
Staphylococcal Infections
Infections with bacteria of the genus STAPHYLOCOCCUS.		01.9610
Kidney Diseases
Pathological processes of the KIDNEY or its component tissues.		01.9610
Bleb
[description not available]		01.9610