Tìm theo
Trimetrexate
Các tên gọi khác (9 ) :
  • CI-898
  • Neutrexin
  • SID26755046
  • SID50110873
  • TMQ
  • TMX
  • Trimetrexate
  • Trimetrexato
  • Trimetrexatum
antifungal agents, antiprotozoal agents, folic acid antagonists, antimetabolites antineoplastic, antibio
Thuốc Gốc
Small Molecule
CAS: 52128-35-5
ATC: P01AX07
ĐG : Ben Venue Laboratories Inc. , http://www.benvenue.com
CTHH: C19H23N5O3
PTK: 369.4176
A nonclassical folic acid inhibitor through its inhibition of the enzyme dihydrofolate reductase. It is being tested for efficacy as an antineoplastic agent and as an antiparasitic agent against pneumocystis pneumonia in AIDS patients. Myelosuppression is its dose-limiting toxic effect. [PubChem]
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C19H23N5O3
Phân tử khối
369.4176
Monoisotopic mass
369.180089627
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)
InChI Key
InChIKey=NOYPYLRCIDNJJB-UHFFFAOYSA-N
IUPAC Name
5-methyl-6-{[(3,4,5-trimethoxyphenyl)amino]methyl}quinazoline-2,4-diamine
Traditional IUPAC Name
trimetrexate
SMILES
COC1=CC(NCC2=C(C)C3=C(C=C2)N=C(N)N=C3N)=CC(OC)=C1OC
Độ tan chảy
215-217 °C
Độ hòa tan
31.4 mg/L
logP
2.55
logS
-4.1
pKa (strongest acidic)
17.04
pKa (Strongest Basic)
7.54
PSA
117.54 Å2
Refractivity
107.7 m3·mol-1
Polarizability
40.24 Å3
Rotatable Bond Count
6
H Bond Acceptor Count
8
H Bond Donor Count
3
Physiological Charge
1
Number of Rings
3
Bioavailability
1
Rule of Five
true
Ghose Filter
true
MDDR-Like Rule
true
pKa
8.0
Dược Lực Học : Trimetrexate, a non-classical folate antagonist, is a synthetic inhibitor of the enzyme dihydrofolate reductase (DHFR). During DNA synthesis and cellular reproduction, folic acid is reduced to tetrahydrofolic acid by the enzyme folic acid reductase. By interfering with the reduction of folic acid, trimetrexate interferes with tissue cell reproduction. Generally, the most sensitive cells to the antimetabolite effect of trimetrexate are those cells which are most actively proliferating such as malignant cells, dermal epithelium, buccal and intestinal mucosa, bone marrow, fetal cells, and cells of the urinary bladder. Because the proliferation of cells in malignant tissues is greater than in most normal tissues, trimetrexate may impair the growth of the malignant tissues without causing irreversible damage to normal tissues. Due to very serious and potentially life-threatening side-effects of this drug, leucovorin must be co-administered for at least 72 hours after the last dose.
Cơ Chế Tác Dụng : A nonclassical folic acid inhibitor through its inhibition of the enzyme dihydrofolate reductase. It is being tested for efficacy as an antineoplastic agent and as an antiparasitic agent against pneumocystis pneumonia in AIDS patients. Myelosuppression is its dose-limiting toxic effect. [PubChem] In vitro studies have shown that trimetrexate is a competitive inhibitor of dihydrofolate reductase (DHFR) from bacterial, protozoan, and mammalian sources. DHFR catalyzes the reduction of intracellular dihydrofolate to the active coenzyme tetrahydrofolate. Inhibition of DHFR results in the depletion of this coenzyme, leading directly to interference with thymidylate biosynthesis, as well as inhibition of folate-dependent formyltransferases, and indirectly to inhibition of p.r.n. biosynthesis. The end result is disruption of DNA, RNA, and protein synthesis, with consequent cell death.
Dược Động Học :

▧ Volume of Distribution :
* 20 ± 8 L/m2 * 36.9 ± 6 L/m2 [cancer patients]
▧ Protein binding :
95% (over the concentration range of 18.75 to 1000 ng/mL)
▧ Metabolism :
Hepatic. Preclinical data strongly suggest that the major metabolic pathway is oxidative O-demethylation, followed by conjugation to either glucuronide or the sulfate.
▧ Route of Elimination :
Ten to 30% of the administered dose is excreted unchanged in the urine.
▧ Half Life :
11 to 20 hours
▧ Clearance :
* 38 +/- 15 mL/min/m2 [patients with acquired immunodeficiency syndrome (AIDS) who had Pneumocystis carinii pneumonia (4 patients) or toxoplasmosis (2 patients). Trimetrexate was administered intravenously as a bolus injection at a dose of 30 mg/m2/day along with leucovorin 20 mg/m2 every 6 hours for 21 days] * 53 +/- 41 mL/min/m2 [Cancer patients with advanced solid tumors using various dosage regimensreceiving a single-dose administration of 10 to 130 mg/m2] * 30 +/- 8 mL/min/m2 [Cancer patients with advanced solid tumors using various dosage regimensafter a five-day infusion]
Độc Tính : The LD50 of intravenous trimetrexate in mice is 62 mg/kg (186 mg/m2). Myelosuppression is a dose-limiting toxic effect.
Chỉ Định : For use, with concurrent leucovorin administration (leucovorin protection), as an alternative therapy for the treatment of moderate-to-severe Pneumocystis carinii pneumonia (PCP) in immunocompromised patients, including patients with the acquired immunodeficiency syndrome (AIDS). Also used to treat several types of cancer including colon cancer.
Tương Tác Thuốc :
  • Acenocoumarol The anticoagulant effect of Acenocoumarol, a Vitamin K antagonist, may be altered by antineoplastics such as Trimetrexate. Monitor for changes in the anticoagulant effects of warfarin and other coumarin derivatives during concomitant use.
  • Digoxin The absorption of Digoxin, a cardiac glycoside, may be decreased by antineoplastic agents such as Trimetrexate. Liquid forms of Digoxin do not appear to be significantly affected. Monitor Digoxin tablet efficacy if Trimetrexate therapy is initiated, discontinued or if the dose is altered.
  • Warfarin The anticoagulant effect of Warfarin, a Vitamin K antagonist, may be altered by antineoplastics such as Trimetrexate. Monitor for changes in the anticoagulant effects of warfarin and other coumarin derivatives during concomitant use.
Liều Lượng & Cách Dùng : Powder, for solution - Intravenous
Dữ Kiện Thương Mại
Nhà Sản Xuất
  • Công ty :
    Sản phẩm biệt dược : Neutrexin
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB01157
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=5583
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46505247
KEGG Compound
http://www.genome.jp/dbget-bin/www_bget?cpd:C11154
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D06238
ChemSpider
http://www.chemspider.com/Chemical-Structure.5381.html
BindingDB
http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=18268
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/58178-020-10
PharmGKB
http://www.pharmgkb.org/drug/PA451790
Wikipedia
http://en.wikipedia.org/wiki/Trimetrexate
RxList
http://www.rxlist.com/cgi/generic2/trimetrexate.htm
Drugs.com
http://www.drugs.com/cdi/trimetrexate.html
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