Trimetrexate

Chemical compound

P01AX07 (WHO)

Pharmacokinetic dataBioavailabilityVD: 20-30 LitersMetabolismOxidative O-demethylation, followed by conjugation with glucuronide or sulfateElimination half-life11 to 12 hoursIdentifiers

IUPAC name

5-methyl-6-[(3,4,5-trimethoxyphenyl) aminomethyl] quinazoline-2,4-diamine

CAS Number

52128-35-5^Y

PubChem CID

5583

IUPHAR/BPS

7613

DrugBank

DB01157^Y

ChemSpider

5381^Y

UNII

UPN4ITI8T4

KEGG

D06238^Y

ChEMBL

ChEMBL119^Y

CompTox Dashboard (EPA)

DTXSID3023714

Chemical and physical dataFormulaC₁₉H₂₃N₅O₃Molar mass369.425 g·mol⁻¹3D model (JSmol)

Interactive image

SMILES

n3c1c(c(c(cc1)CNc2cc(OC)c(OC)c(OC)c2)C)c(nc3N)N

InChI

InChI=1S/C19H23N5O3/c1-10-11(5-6-13-16(10)18(20)24-19(21)23-13)9-22-12-7-14(25-2)17(27-4)15(8-12)26-3/h5-8,22H,9H2,1-4H3,(H4,20,21,23,24)^Y
Key:NOYPYLRCIDNJJB-UHFFFAOYSA-N^Y

(verify)

Trimetrexate is a quinazoline derivative. It is a dihydrofolate reductase inhibitor.^[1]

Uses

It has been used with leucovorin in treating pneumocystis pneumonia.^[2]

It has been investigated for use in treating leiomyosarcoma.^[3] It is a methotrexate (MTX) analog that is active against transport-deficient MTX-resistant tumor cells that overcome the acquired and natural resistance to methotrexate. Other uses include skin lymphoma. ^[4]

References

^ Wong BK, Woolf TF, Chang T, Whitfield LR (1990). "Metabolic disposition of trimetrexate, a nonclassical dihydrofolate reductase inhibitor, in rat and dog". Drug Metab. Dispos. 18 (6): 980–6. PMID 1981548.
^ Sattler FR, Allegra CJ, Verdegem TD, et al. (January 1990). "Trimetrexate-leucovorin dosage evaluation study for treatment of Pneumocystis carinii pneumonia". J. Infect. Dis. 161 (1): 91–6. doi:10.1093/infdis/161.1.91. PMID 2136905.
^ Smith HO, Blessing JA, Vaccarello L (January 2002). "Trimetrexate in the treatment of recurrent or advanced leiomyosarcoma of the uterus: a phase II study of the Gynecologic Oncology Group". Gynecol. Oncol. 84 (1): 140–4. doi:10.1006/gyno.2001.6482. PMID 11748990.
^ Trimetrexate in relapsed T-cell lymphoma with skin involvement. J Clin Oncol. 2002 Jun 15;20(12):2876-80.

External links

MedlinePlus DrugInfo uspdi-202693
Diseases Database (DDB): 30480

Antiparasitics – antiprotozoal agents – Chromalveolata antiparasitics (P01)

Alveo-
late

Apicom-
plexa

Conoidasida/
(Coccidiostats)

Cryptosporidiosis	thiazolides (nitazoxanide)
Isosporiasis	trimethoprim/sulfamethoxazole^#
Toxoplasmosis	pyrimethamine sulfadiazine clindamycin atovaquone

Aconoidasida

Malaria

Individual
agents

Hemozoin
inhibitors

Aminoquinolines	(4-): amodiaquine^# chloroquine^# hydroxychloroquine^# (8-): primaquine^# pamaquine^‡ tafenoquine
4-Methanolquinolines	mefloquine^# quinine^# quinidine
Other	lumefantrine + artemether^# halofantrine

Antifolates

DHFR inhibitors	pyrimethamine cycloguanil biguanides chlorproguanil proguanil^#
Sulfonamides	sulfadoxine sulfalene
Co-formulation	sulfadoxine/pyrimethamine (SP)^#

Sesquiterpene
lactones

Other

Combi-
nations

Fixed-dose (co-formulated) ACTs	artemether/lumefantrine^# arterolane/piperaquine artesunate/amodiaquine (ASAQ) artesunate/mefloquine (ASMQ) artesunate/pyronaridine piperaquine/dihydroartemisinin
Other combinations (not co-formulated)	artesunate/mefloquine artesunate/SP quinine/clindamycin quinine/doxycycline quinine/tetracycline