70280-71-6

Basic information

• Product Name: diethyl N-<4-(ethylamino)benzoyl>-L-glutamate
• Synonyms: diethyl N-<4-(ethylamino)benzoyl>-L-glutamate
• CAS NO: 70280-71-6
• Molecular Weight: 350.415
• Mol File: 70280-71-6.mol
• Article Data: 2

Chemical Properties

• CAS DataBase Reference: diethyl N-<4-(ethylamino)benzoyl>-L-glutamate(CAS DataBase Reference)
• NIST Chemistry Reference: diethyl N-<4-(ethylamino)benzoyl>-L-glutamate(70280-71-6)
• EPA Substance Registry System: diethyl N-<4-(ethylamino)benzoyl>-L-glutamate(70280-71-6)

Safety Data

• Hazardous Substances Data: 70280-71-6(Hazardous Substances Data)

Upstream product

• 13726-52-8 diethyl N-(p-aminobenzoyl)-L-glutamate 
• 75-03-6 ethyl iodide 

Downstream Products

• 106585-60-8 Diethyl N-(4-(N-((3,4-dihydro-4-oxo-3-((pivaloyl)oxy) methyl-6-quinazolinyl)methyl)ethylamino)benzoyl)-L-glutamate 
• 131078-75-6 (S)-2-{4-[Ethyl-(4-methylsulfanyl-quinazolin-6-ylmethyl)-amino]-benzoylamino}-pentanedioic acid diethyl ester 
• 101810-78-0 N-<4-<<(2,4-diamino-5-methylpyrido<2,3-d>pyrimidin-6-yl)methyl>ethylamino>benzoyl>-L-glutamic acid diethyl ester 
• 123637-84-3 (S)-2-(4-{[2-(2,2-Dimethyl-propionylamino)-4-methoxy-quinolin-6-ylmethyl]-ethyl-amino}-benzoylamino)-pentanedioic acid diethyl ester 
• 118111-79-8 (S)-2-{4-[(2,4-Dimethoxy-quinazolin-6-ylmethyl)-ethyl-amino]-benzoylamino}-pentanedioic acid diethyl ester 
• 106585-68-6 N-(4-(N-((3,4-dihydro-4-oxo-6-quinazolinyl)methyl) ethylamino)benzoyl)-L-glutamic acid 
• 112888-05-8 (S)-2-{4-[Ethyl-(2-methoxy-4-oxo-3,4-dihydro-quinazolin-6-ylmethyl)-amino]-benzoylamino}-pentanedioic acid 
• 101810-80-4 5-methyl-5-deaza-10-ethylaminopterin 
• 112887-74-8 p-[ N-(3,4-dihydro-2-hydroxymethyl-4-oxoquinazolin-6-ylmethyl)-N-ethylamino]benzoyl-L-glutamic acid 
• 112887-77-1 N - p-[ N-(3,4-dihydro-2-methyl-4-oxoquinazolin-6-ylmethyl)-N-ethylamino]benzoyl-L-glutamic acid 
• 123637-22-9 N-[4-[N-(2amino-4-methoxyquinolin-6-ylmethyl)-N-ethylamino]benzoyl]-L-glutamic acid 

Relevant articles and documents

Quinazoline antifolates inhibiting thymidylate synthase: 2-Desamino derivatives with enhanced solubility and potency

The poor solubility of the thymidylate synthase (TS) inhibiting antifolate 10-propargyl-5,8-dideazafolic acid has posed problems for its clinical use and is probably responsible for its renal toxicity. The insolubility is caused by the 2-amino-3,4-dihydro-4-oxopyridimine moiety of the drug which stabilizes the solid state by intermolecular hydrogen bonding. In examining this moiety we have removed the 2-amino group and now report on 2-desamino-10-propargyl-5,8-dideazafolic acid (8e) and four analogues with H, Me, Et, and allyl at N10. 3,4-Dihydro-4-oxo-6-methylquinazoline was solubilized by alkylating the lactam nitrogen with chloromethyl pivalate. Reaction with N-bromosuccinimide gave the corresponding 6-bromomethyl compound, which was coupled with diethyl N-(4-aminobenzoyl)-L-glutamate or the appropriate N-substituted derivative thereof. The quinazoline N3 nitrogen and carboxyl groups in the product were simultaneously deprotected by cold alkali in the final step to give the desired five antifolates. These were tested against L1210 TS and its was found that removal of the 2-amino group caused a slight (3-9-fold) loss of TS inhibition. 8e was only 8-fold a lesser TS inhibitor than the parent drug. Inhibition of rat liver dihydrofolate reductase was reduced by over 1 order of magnitude for three compounds tested. All five analogues were more cytotoxic to L1210 cells in culture than their 2-amino counterparts; 8e was 8.5-fold more active with an ID50 of 0.4 μM. This remarkable result probably owes to increased cellular penetration. 8e was 5-fold more soluble than 1 at pH 5.0 and > 340-fold more soluble at pH 7.4.