Raltitrexed Chemical Properties

Melting point:

176-1800C

Density 

1.49±0.1 g/cm3(Predicted)

storage temp. 

2-8°C

solubility 

H2O: ≥10mg/mL

pka

3.50±0.10(Predicted)

form 

solid

color 

off-white to light yellow

InChIKey

IVTVGDXNLFLDRM-HNNXBMFYSA-N

CAS DataBase Reference

112887-68-0(CAS DataBase Reference)

Safety Information

Hazard Codes 

Xi,T

Risk Statements 

36/38-25-61

Safety Statements 

26-37/39-45-53

RIDADR 

UN 2811 6.1 / PGIII

WGK Germany 

2

HS Code 

2934.99.4700

Raltitrexed Usage And Synthesis

Description

Tomudex was launched in Ireland, France, Luxembourg and the UK for advanced colorectal cancer and it was prepared in a convergent manner (6 steps) from diethyl L-glutamate and 6-bromomethyi-2-methyl-quinazolin4(3H)-one. Tomudex is a highly selective inhibitor of thymidylate synthase (TS), the key enzyme in the biochemical conversion of dUMP to dTMP. It enters the cell via the reduced folatefmethotrexate cell membrane carrier and is converted to the polyglutamate species by folylpolyglutamate synthase within 4h where it then binds to the folate substrate site of TS. Clinically, it had a 29% response rate in patients with advanced colorectal cancer. It is water soluble, can be administered as a single dose every three weeks and had no hepto- or nephrotoxicity.

Chemical Properties

Yellow Crystalline Powder

Originator

Zeneca (UK)

Uses

Folate-based inhibitor of thymidylate synthase; rapidly and extensively metabolized to its more potent polyglutamate derivatives. Antineoplastic

Definition

ChEBI: ICI D1694 is a N-acyl-amino acid.

brand name

Tomudex (Zeneca).

Biochem/physiol Actions

Raltitrexed is a folate-based inhibitor of thymidylate synthase (TS) that is rapidly and extensively metabolized to its more potent polyglutamate derivatives. By inhibiting the formation of precursor pyrimidine nucleotides, raltitrexed prevents the formation of DNA and RNA, which are required for the growth and survival of both normal cells and cancer cells.

Clinical Use

Treatment of colorectal cancer when fluorouracil and folinic acid cannot be used

Drug interactions

Potentially hazardous interactions with other drugs
Antipsychotics: avoid with clozapine, increased risk of agranulocytosis.
Folic and folinic acid: impairs cytotoxic action - avoid.

Metabolism

Raltitrexed is actively transported into cells and metabolised to active polyglutamate forms.
The remainder of a dose is not metabolised and is excreted unchanged, about 50% of a dose appearing in the urine, and about 15% in the faeces.

Raltitrexed(112887-68-0)Related Product Information

• Y27632 (hydrochloride)
• 5-Fluorouracil
• Bosutinib
• Pemetrexed Disodium
• BI 2536
• Methotrexate
• Milrinone
• Quinazoline
• 2-AMINO-5-METHYLBENZAMIDE
• Raltitrexed
• 5-(DIMETHYLAMINO)THIOPHENE-2-CARBALDEHYDE
• 4-HYDROXY-6-METHYLQUINAZOLINE
• 1400W
• 3-DIMETHYLAMINOMETHYL-BENZYLAMINE
• 2-[(2-thienylmethyl)amino]-1-butanol
• (THIOPHENE-2-CARBONYL)-AMINO]-ACETIC ACID
• 6-(bromomethyl)-3,4-dihydro-2-methyl-4-oxoquinazoline (intermediate of raltitrexed)
• 5-nitro-2-thiophenic acid (intermediate of raltitrexed)