137464-99-4

Upstream product

• 137464-98-3 4-(4-oxocyclohexyl)benzoic acid methyl ester 
• 616-38-6 carbonic acid dimethyl ester 
• 4746-97-8 cyclohexanedione monoethylene ketal 
• 623-00-7 4-bromobenzenecarbonitrile 
• 137465-00-0 4-(4-carbomethoxyphenyl)-2,4-dicarbomethoxycyclohexanone 
• 137464-97-2 4-(4'-carbomethoxyphenyl)-4-hydroxycyclohexanone ethylene ketal 
• 137464-96-1 4-(4'-carboxyphenyl)-4-hydroxycyclohexanone ethylene ketal 
• 137464-95-0 4-(4'-cyanophenyl)-4-hydroxycyclohexanone ethylene ketal 
• 137465-01-1 4-(4-oxocyclohexyl)benzoic acid 
• 52787-14-1 methyl 4-(2-methoxy-2-oxoethyl)benzoate 

Downstream Products

• 137465-02-2 methyl 4-amino-4-deoxy-5,10-ethano-7-hydroxy-5,10-dideazapteroate 
• 137465-06-6 5,10-ethano-5,10-dideazaaminopterin diethyl ester 
• 137465-07-7 5,10-ethano-5,10-dideazaaminopterin 
• 137465-03-3 4-(1,3-Diamino-5,6,7,8,9,10-hexahydro-pyrimido[4,5-c]isoquinolin-8-yl)-benzoic acid methyl ester 
• 137465-04-4 methyl 4-amino-4-deoxy-5,10-ethano-5,10-dideazapteroate 
• 137465-05-5 pteroic acid 

Relevant academic research and scientific papers

Synthesis and antifolate properties of 5,10-ethano-5,10-dideazaaminopterin

2-Carbomethoxy-4-(p-carbomethoxyphenyl)cyclohexanone was prepared in a four-step process and thermally condensed with 2,4,6-triaminopyrimidine to afford methyl 2,4-diamino-4-deoxy-7-hydroxy-5,10-ethano-5,10-dideazapteroate. Reduction of the 7-oxo function with borane gave the 7,8-dihydro pterin which was subsequently oxidized to the fully aromatic pteroate ester with dicyanodichlorobenzoquinone. Saponification of the benzoate ester, coupling with diethyl glutamate and final ester hydrolysis afforded the title compound. This novel deazaaminopterin analogue was approximately as potent as methotrexate in vitro in terms of DHFR and L1210 cell growth inhibition. There are indications of diastereomeric differences in the enzyme inhibition measurements. A significant transport advantage over MTX for influx into L1210 cells was observed. The compound was active against the E 0771 murine mammary solid tumor, but further investigation with individual diastereomers is required to define the ED50.

Cyclized 5,10-dideazaaminopterin compounds

5,10-Dialkyl substituted 5,10-dideazaaminopterins and a cyclized derivative thereof are disclosed as potent antineoplastic agents. Also disclosed is an improved process for the preparation of 10-ethyl-10-deazaaminopterin using the intermediate methyl 4-[[2-(2,4-diamino-6-pteridinyl)-1-ethyl]ethenyl]benzoate.