112887-68-0 Usage
Description
Raltitrexed, also known as Tomudex, is a folate-based inhibitor of thymidylate synthase (TS), a key enzyme in the biochemical conversion of dUMP to dTMP. It is a yellow crystalline powder that is rapidly and extensively metabolized to its more potent polyglutamate derivatives, making it an effective antineoplastic agent.
Uses
Used in Anticancer Applications:
Raltitrexed is used as an antineoplastic agent for the treatment of advanced colorectal cancer. It is a highly selective inhibitor of thymidylate synthase (TS) and enters the cell via the reduced folate/methotrexate cell membrane carrier. Once inside the cell, it is converted to the polyglutamate species by folylpolyglutamate synthase within 4 hours, where it then binds to the folate substrate site of TS. Clinically, Raltitrexed has demonstrated a 29% response rate in patients with advanced colorectal cancer.
Used in Pharmaceutical Industry:
Raltitrexed is used as a key component in the development of Tomudex, a brand name drug launched in Ireland, France, Luxembourg, and the UK. It is prepared in a convergent manner through a six-step process from diethyl L-glutamate and 6-bromomethyi-2-methyl-quinazolin4(3H)-one. Tomudex is water-soluble, allowing for single-dose administration every three weeks, and has shown no hepatoor nephrotoxicity, making it a safer alternative for cancer treatment.
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.
Check Digit Verification of cas no
The CAS Registry Mumber 112887-68-0 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,1,2,8,8 and 7 respectively; the second part has 2 digits, 6 and 8 respectively.
Calculate Digit Verification of CAS Registry Number 112887-68:
(8*1)+(7*1)+(6*2)+(5*8)+(4*8)+(3*7)+(2*6)+(1*8)=140
140 % 10 = 0
So 112887-68-0 is a valid CAS Registry Number.
InChI:InChI=1/C20H24N4O2S/c1-12-21-15-7-6-13(10-14(15)18(25)22-12)11-24(5)17-9-8-16(27-17)19(26)23-20(2,3)4/h6-10H,11H2,1-5H3,(H,23,26)(H,21,22,25)
112887-68-0Relevant articles and documents
New synthesis of thymidylate synthase inhibitor raltitrexed
Cao, Sheng-Li,Wan, Rong,Feng, Yu-Ping
, p. 3519 - 3526 (2003)
The quinazoline-based inhibitor of thymidylate synthase, Raltitrexed, was synthesized from 2,5-thiophenedicarboxylic acid via monocoupling with diethyl L-glutamate, modified Curtius reaction, N-methylation, removal of Boc-protecting group, condensation with (bromomethyl)quinazolinone and saponification in 18.2% overall yield.
Raltitrexed pharmaceutical composition and preparation method thereof
-
, (2018/04/02)
The invention relates to a raltitrexed pharmaceutical composition which is high in safety and a preparation method thereof. The raltitrexed pharmaceutical composition comprises raltitrexed and thiophene related substances, wherein the content of the thiophene related substances is not higher than 0.3%. The raltitrexed pharmaceutical composition is good in safety, effectiveness and stability and can relieve the blood toxicity of the raltitrexed to a certain degree.
Anti-tumour agents
-
, (2008/06/13)
A quinazoline of the formula: STR1 wherein R1 is alkyl, cycloalkyl, alkenyl, alkynyl, alkoxy, alkylthio, aryl, aryloxy, arylalkyl, halogeno, hydroxy, mercapto, pyridylthio, pyrimidinylthio, or substituted alkyl or alkoxy; wherein R2 is hydrogen, alkyl, alkenyl, alkynyl, substituted alkyl or alkanoyl; wherein Ar is phenylene, naphthylene or heterocyclene which is unsubstituted or bears one or more substituents and wherein R3 is such that R3 --NH2 is an amino acid; or a pharmaceutically-acceptable salt or ester thereof. The compounds possess anti-tumour activity.
