112887-62-4

Basic information

• Product Name: N-(4-{[(2-methyl-4-oxo-1,4-dihydroquinazolin-6-yl)methyl](prop-2-yn-1-yl)amino}benzoyl)-L-glutamic acid
• CAS NO: 112887-62-4
• Molecular Formula: C₂₅H₂₄N₄O₆
• Molecular Weight: 476.4813
• Mol File: 112887-62-4.mol
• Article Data: 4

Chemical Properties

• Density: 1.33g/cm³
• Refractive Index: 1.638
• CAS DataBase Reference: N-(4-{[(2-methyl-4-oxo-1,4-dihydroquinazolin-6-yl)methyl](prop-2-yn-1-yl)amino}benzoyl)-L-glutamic acid(CAS DataBase Reference)
• NIST Chemistry Reference: N-(4-{[(2-methyl-4-oxo-1,4-dihydroquinazolin-6-yl)methyl](prop-2-yn-1-yl)amino}benzoyl)-L-glutamic acid(112887-62-4)
• EPA Substance Registry System: N-(4-{[(2-methyl-4-oxo-1,4-dihydroquinazolin-6-yl)methyl](prop-2-yn-1-yl)amino}benzoyl)-L-glutamic acid(112887-62-4)

Safety Data

• Hazardous Substances Data: 112887-62-4(Hazardous Substances Data)

Upstream product

• 112888-39-8 6-bromomethyl-3,4-dihydro-2-methyl-4-oxo-3-((pivaloyl)oxy)methylquinazoline 
• 76858-72-5 diethyl N-(4-(prop-2-ynylamino)benzoyl)-L-glutamate 
• 112888-43-4 4(3H)-oxo-6-(bromomethyl)-2-methyl quinazoline 
• 18731-19-6 3,4-dihydro-2,6-dimethyl-4-oxoquinazoline 
• 2941-78-8 2-Amino-5-methylbenzoic acid 
• 119820-58-5 (S)-2-{4-[(4-Acetylamino-3-carboxy-benzyl)-prop-2-ynyl-amino]-benzoylamino}-pentanedioic acid diethyl ester 
• 119820-57-4 2-acetamido-5-(bromomethyl)benzoic acid 
• 67081-68-9 2-acetamido-5-methylbenzoic acid 

Downstream Products

• 138899-61-3 (S)-2-[(S)-4-Carboxy-4-((S)-4-carboxy-4-{4-[(2-methyl-4-oxo-3,4-dihydro-quinazolin-6-ylmethyl)-prop-2-ynyl-amino]-benzoylamino}-butyrylamino)-butyrylamino]-pentanedioic acid; compound with trifluoro-acetic acid 
• 138899-58-8 C₆₀H₈₅N₇O₁₅ 
• 138899-60-2 (S)-2-((S)-4-Carboxy-4-{4-[(2-methyl-4-oxo-3,4-dihydro-quinazolin-6-ylmethyl)-prop-2-ynyl-amino]-benzoylamino}-butyrylamino)-pentanedioic acid; compound with trifluoro-acetic acid 
• 138899-57-7 (S)-2-[(S)-4-tert-Butoxycarbonyl-4-((S)-4-tert-butoxycarbonyl-4-{4-[(2-methyl-4-oxo-3,4-dihydro-quinazolin-6-ylmethyl)-prop-2-ynyl-amino]-benzoylamino}-butyrylamino)-butyrylamino]-pentanedioic acid di-tert-butyl ester 
• 138899-56-6 (S)-2-((S)-4-tert-Butoxycarbonyl-4-{4-[(2-methyl-4-oxo-3,4-dihydro-quinazolin-6-ylmethyl)-prop-2-ynyl-amino]-benzoylamino}-butyrylamino)-pentanedioic acid di-tert-butyl ester 
• 138899-63-5 (S)-2-((S)-4-Carboxy-4-{(S)-4-carboxy-4-[(S)-4-carboxy-4-((S)-4-carboxy-4-{4-[(2-methyl-4-oxo-3,4-dihydro-quinazolin-6-ylmethyl)-prop-2-ynyl-amino]-benzoylamino}-butyrylamino)-butyrylamino]-butyrylamino}-butyrylamino)-pentanedioic acid; compound with trifluoro-acetic acid 
• 138899-62-4 (S)-2-{(S)-4-Carboxy-4-[(S)-4-carboxy-4-((S)-4-carboxy-4-{4-[(2-methyl-4-oxo-3,4-dihydro-quinazolin-6-ylmethyl)-prop-2-ynyl-amino]-benzoylamino}-butyrylamino)-butyrylamino]-butyrylamino}-pentanedioic acid; compound with trifluoro-acetic acid 
• 138899-59-9 C₆₉H₁₀₀N₈O₁₈ 
• 112888-70-7 p-[N-(2-methyl-4-oxo-3,4-dihydroquinazolin-6-ylmethyl)-N-(prop-2-ynyl)amino]benzoic acid 
• 133933-15-0 2-desamino-2-methyl-N¹⁰-propargyl-5,8-dideaza-1,2-dihydrofolic acid 

Relevant articles and documents

Anti-tumour agents

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.

Quinazoline antifolate thymidylate synthase inhibitors: Alkyl, substituted alkyl, and aryl substituents in the C2 position

Modification of the potent thymidylate synthase (TS) inhibitor N-[4-[N-[(2-amino-3,4-dihydro-4-oxo-6-quinazolinyl)methyl]-N-prop-2-yn ylamino]benzoyl]-L-glutamic acid (1a) has led to the synthesis of quinazoline antifolates bearing alkyl, substituted alkyl, and aryl substituents at C2. In general the synthetic route involved the coupling of the appropriate diethyl N-[4-(alkylamino)benzoyl]-L-glutamate with a C2-substituted 6-(bromo-methyl)-3,4-dihydro-4-oxoquinazoline followed by deprotection using mild alkali. Good enzyme inhibition and cytotoxicity were found with compounds containing small nonpolar groups in the C2 position with the 2-desamino-2-methyl analogue 3a being the most potent. Larger C2 substituents were tolerated by the enzyme, but cytotoxicity was reduced. Highly potent series were followed up by the synthesis of a number of analogues in which the N10 substituent was varied. In this manner a number of interesting TS inhibitors have been prepared. Although none of these was more potent than 1a against the isolated enzyme, over half of the compounds prepared were more potent as cytotoxic agents against L1210 cells in culture. The potential of such compounds as useful antitumor agents was further enhanced by the finding that the improved aqueous solubilities of compounds such as 3a over 1a were reflected in vivo in that 3a was at least 5 times less toxic to mice than 1a.