80576-83-6

Basic information

• Product Name: Edatrexate
• Synonyms: Edatrexate;PSYLLIUMSEED;2-[[4-[1-(2,4-Diaminopteridin-6-yl)butan-2-yl]benzoyl]amino]pentanedioic acid;N-(4-(1-((2,4-Diamino-6-pteridinyl)methyl)propyl)benzoyl)-L-glutamic acid;(S)-2-[4-[1-[(2,4-Diaminopteridine-6-yl)methyl]propyl]benzoylamino]pentanedioic acid;10-Ethyl-10-deazaaminopterin;10-Ethyl-10-deazaaminopterine;EDX
• CAS NO: 80576-83-6
• Molecular Formula: C₂₂H₂₅N₇O₅
• Molecular Weight: 467.48
• Mol File: 80576-83-6.mol
• Article Data: 3

Chemical Properties

• Appearance: /
• Density: 1.441 g/cm³
• Refractive Index: 1.686
• PKA: 3.56±0.10(Predicted)
• CAS DataBase Reference: Edatrexate(CAS DataBase Reference)
• NIST Chemistry Reference: Edatrexate(80576-83-6)
• EPA Substance Registry System: Edatrexate(80576-83-6)

Safety Data

• Hazardous Substances Data: 80576-83-6(Hazardous Substances Data)

Usage

Uses

Antineoplastic.

InChI:InChI=1/C22H25N7O5/c1-2-11(9-14-10-25-19-17(26-14)18(23)28-22(24)29-19)12-3-5-13(6-4-12)20(32)27-15(21(33)34)7-8-16(30)31/h3-6,10-11,15H,2,7-9H2,1H3,(H,27,32)(H,30,31)(H,33,34)(H4,23,24,25,28,29)/t11?,15-/m0/s1

Upstream product

• 1118-89-4 diethyl-L-glutamate hydrochloride 
• 80576-82-5 diethyl N-<4-<1-<(2,4-diamino-6-pteridinyl)methyl>propyl>benzoyl>-L-glutamate 
• 151071-45-3 methyl 4-<2-(2,4-diamino-6-pteridinyl)-1-ethylethenyl>benzoate 
• 142721-22-0 methyl 4-<1-<(2,4-diamino-6-pteridinyl)methyl>propyl>benzoate 
• 80576-79-0 4-(3-Bromo-1-ethyl-4-oxo-butyl)-benzoic acid 
• 80576-81-4 4-[1-(2,4-Diamino-pteridin-6-ylmethyl)-propyl]-benzoic acid 
• 2438-05-3 4-n-propylbenzoic acid 

Relevant articles and documents

Synthesis and antifolate evaluation of 10-ethyl-5-methyl-5,10- dideazaaminopterin and an alternative synthesis of 10-ethyl-10- deazaaminopterin (edatrexate)

Previous findings suggesting that 5,10-dialkyl-substituted derivatives of 5,10-dideazaaminopterin warranted study as potential antifolates prompted synthesis of 10-ethyl-5-methyl-5,10-dideazaaminopterin (12a). The key step in the synthetic route to 12a was Wittig condensation of the tributylphosphorane derived from 6-(bromomethyl)-2,4-diamino-5-methylpyrido[2,3-d]pyrimidine (7a) with methyl 4-propionylbenzoate. Reaction conditions for the Wittig condensation were developed using the tributylphosphorane prepared from 6- (bromomethyl)-2,4-pteridinediamine (7b) as a model. Each of the respective Wittig products 8a and 8b was obtained in 75-80% yield. Hydrogenation of 8a and 8b at their 9,10-double bond afforded 4-amino-4-deoxy-10-ethyl-5-methyl- 5,10-dideazapteroic acid methyl ester (9a) and 4-amino-4-deoxy-10-ethyl-10- deazapteroic acid methyl ester (9b). This route to 9b intersects reported synthetic approaches leading to 10-ethyl-10-deazaaminopterin (10-EDAM, edatrexate), an agent now in advanced clinical trials. Thus the Wittig approach affords an alternative synthetic route to 10-EDAM. Remaining steps were ester hydrolysis of 9a,b to give carboxylic acids 10a,b followed by standard peptide coupling with diethyl L-glutamate to produce diethyl esters 11a,b, which on hydrolysis gave 12a and 10-EDAM (12b), respectively. The relative influx of 12a was enhanced about 3.2-fold over MTX, but as an inhibitor of dihydrofolate reductase (DHFR) from L1210 cells and in the inhibition of L1210 cell growth in vitro, this compound was approximately 20- fold less effective than MTX (DHFR inhibition, K(i) = 4.82 ± 0.60 pM for MTX, 100 pM for 12a; cell growth, IC50 = 3.4 ± 1.0 nM for MTX, 65 ± 18 nM for 12a).

Synthesis and antitumor activity of 10-alkyl-10-deazaminopterins. A convenient synthesis of 10-deazaminopterin

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