Trimetrexate

Trimetrexate

Systematic (IUPAC) name
5-methyl-6-[(3,4,5-trimethoxyphenyl) aminomethyl] quinazoline-2,4-diamine
Clinical data
AHFS/Drugs.com	Consumer Drug Information
MedlinePlus	a694019
Pregnancy cat.	?
Legal status	?
Pharmacokinetic data
Bioavailability	VD: 20-30 Liters
Metabolism	Oxidative O-demethylation, followed by conjugation with glucuronide or sulfate
Half-life	11 to 12 hours
Identifiers
CAS number	52128-35-5^Y
ATC code	P01AX07
PubChem	CID 5583
DrugBank	APRD00268
ChemSpider	5381^Y
UNII	UPN4ITI8T4^Y
KEGG	D06238^N
ChEMBL	CHEMBL119^Y
Chemical data
Formula	C₁₉H₂₃N₅O₃
Mol. mass	369.418 g/mol
SMILES	eMolecules & PubChem
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
N(what is this?) (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. http://dmd.aspetjournals.org/cgi/pmidlookup?view=long&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. 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. http://linkinghub.elsevier.com/retrieve/pii/S0090825801964820.
^ 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
DDB 30480

Antiparasitics – antiprotozoal agents – Chromalveolate antiparasitics (P01)

Alveo-
late

Apicom-
plexa

Conoidasida/
(Coccidiostats)

Cryptosporidiosis	thiazole (Nitazoxanide)

Isosporiasis	Trimethoprim/sulfamethoxazole^#

Toxoplasmosis	Pyrimethamine • Sulfadiazine

Aconoidasida

Malaria

Individual
agents

Hemozoin
inhibitors

Aminoquinolines	(4-): Amodiaquine^# • Chloroquine^# • Hydroxychloroquine (8-): Primaquine^# • Pamaquine

4-methanolquinolines	Mefloquine^#• Quinine^# • Quinidine

Other	Lumefantrine (combined with artemether) Halofantrine Pyronaridine

Antifolates

DHFR inhibitors (antifols)	2,4-Diaminopyrimidines (pyrimethamine) biguanides (proguanil^# • chlorproguanil)

Sulfonamides	Sulfadoxine • sulfamethoxypyrazine

Coformulation	Fansidar^# (sulfadoxine/pyrimethamine)

Sesquiterpene
lactones

Artemether^# • Artesunate^#• Dihydroartemisinin •
Arteether/Artemotil • Artemisinin

Other

Atovaquone (as Malarone)
Tetracycline • Doxycycline^#
Clindamycin

Combi-
nations

Fixed-dose (coformulated) ACTs	artemether-lumefantrine^# artesunate-amodiaquine (ASAQ) artesunate-mefloquine (ASMQ) dihydroartemisinin-piperaquine artesunate-pyronaridine

Other combinations (not co-formulated)	artesunate/SP • artesunate/mefloquine • quinine/tetracycline • quinine/doxycycline • quinine/clindamycin

Babesiosis

Clindamycin

Cilio-
phora

Balantidiasis: Tetracycline

Hetero-
kont

Blastocystosis: Metronidazole

^#WHO-EM. ^‡Withdrawn from market. Clinical trials: ^†Phase III. ^§Never to phase III

M: PRO

ambz, excv, chrm (strc)

ambz, excv, chrm