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112887-68-0

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112887-68-0 Usage

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

Uses

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

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.

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)

112887-68-0SDS

SAFETY DATA SHEETS

According to Globally Harmonized System of Classification and Labelling of Chemicals (GHS) - Sixth revised edition

Version: 1.0

Creation Date: Aug 17, 2017

Revision Date: Aug 17, 2017

1.Identification

1.1 GHS Product identifier

Product name Raltitrexed

1.2 Other means of identification

Product number -
Other names (2S)-2-[[5-[methyl-[(2-methyl-4-oxo-1H-quinazolin-6-yl)methyl]amino]thiophene-2-carbonyl]amino]pentanedioic acid

1.3 Recommended use of the chemical and restrictions on use

Identified uses For industry use only.
Uses advised against no data available

1.4 Supplier's details

1.5 Emergency phone number

Emergency phone number -
Service hours Monday to Friday, 9am-5pm (Standard time zone: UTC/GMT +8 hours).

More Details:112887-68-0 SDS

112887-68-0Downstream Products

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.

Quinazoline Antifolate Thymidylate Synthase Inhibitors: Heterocyclic Benzoyl Ring Modifications

Marsham, Peter R.,Hughes, Leslie R.,Jackman, Ann L.,Hayter, Anthony J.,Oldfield, John,et al.

, p. 1594 - 1605 (2007/10/02)

The synthesis is described of a series of C2-methyl-N10-alkylquinazoline-based antifolates in which the p-aminobenzoate ring is replaced by the heterocycles thiophene, thiazole, thiadiazole, pyridine, and pyrimidine.These were generally elaborated by the reaction of (bromomethyl)quinazoline 18 or its N3--protected derivative 36 with suitable heterocyclic amines although each heterocyclic system required its own particular synthetic approach.The compounds were tested as inhibitors of partially purified L1210 thymidylate synthase (TS).Theywere also examined for their inhibition of the growth of L1210 cells in culture.The thiophene system 7 and its related thiazole 8 gave analogues that were considerably more potent than the parent benzene series 2 as inhibitors of L1210 cell growth although in general these heterocycles were somewhat poorer inhibitors of the isolated TS enzyme.The enhanced cytotoxicities of the thiophene and thiazole analogues result, at least in part, from their efficient transport into the cells via the reduced folate carrier mechanism and very good substrate activity for folypolyglutamate synthetase.The replacement of the C2-methyl group by C2-(fluoromethyl) and C2-(hydroxymethyl) substituents in the thiophene and thiazole series gave derivatives that were only slightly less potent inhibitors of the TS enzyme but which were considerably less cytotoxic.

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