113859-36-2

Upstream product

• 13726-52-8 diethyl N-(p-aminobenzoyl)-L-glutamate 
• 113859-31-7 (2,4-Diamino-7-methyl-5-phenyl-pyrido[2,3-d]pyrimidin-6-yl)-methanol; hydrochloride 
• 113859-19-1 2-Methanesulfonyl-5-methoxymethoxymethyl-6-methyl-4-phenyl-nicotinonitrile 
• 113859-25-9 6-Methoxymethoxymethyl-7-methyl-5-phenyl-pyrido[2,3-d]pyrimidine-2,4-diamine 
• 113859-13-5 5-Methoxymethoxymethyl-6-methyl-2-methylsulfanyl-4-phenyl-nicotinonitrile 
• 113859-01-1 5-Cyano-2-methyl-6-methylsulfanyl-4-phenyl-nicotinic acid ethyl ester 
• 113859-07-7 5-Hydroxymethyl-6-methyl-2-methylsulfanyl-4-phenyl-nicotinonitrile 
• 97651-26-8 3-cyano-5-(ethoxycarbonyl)-6-methyl-4-phenylpyridine-2(1H)-thione 
• 569-37-9 ethyl 3-oxo-2-benzoylbutanoate 

Downstream Products

• 113859-41-9 N-pyrimidin-6-yl)methyl>amino>benzoyl>-L-glutamic acid 

Relevant academic research and scientific papers

Chemical synthesis and biological activities of 5-deazaaminopterin analogues bearing substituent(s) at the 5- and/or 7-position(s)

Condensation of cyanothioacetamide (4) with ethyl α-(ethoxymethylene)acetoacetate (5b), ethyl 4-ethoxy-2-(ethoxymethylene)-3-oxobutanoate (5c), ethyl 2-(ethoxymethylene)-3-oxo-4-phenylpropanoate (5d) afforded exclusively the corresponding 6-substituted pyridines (6b-d). Cyclization of 4 with 3-carbethoxybutane-2,4-dione (5e) gave 3-cyano-5-(ethoxycarbonyl)-4,6-dimethylpyridine-2(1H)-thione (6e), whereas reaction of 4 with 3-carbethoxy-1-phenylpropane-1,3-dione (5f) yielded two products, 3-cyano-5-(ethoxycarbonyl)-4-methyl-6-phenylpyridine-2(1H)-thione (6f) and the 6-methyl-4-phenyl isomer 6g. The structural assignments for 6f and 6g are made on the basis of 1H and 13C NMR spectral analyses of the 2-(methylthio)nicotinates (7f,g) prepared from 6f and 6g by treatment with MeI/K2CO3. Nicotinates 7b,d-g were converted into their corresponding 2,4-diaminopyrido[2,3-d]pyrimidines 12b,d-g in five steps, via reduction, protection, oxidation, condensation with guanidine, and deprotection. The 7-mono- and 5,7-disubstituted-5-deazaaminopterins (1b,d-g) were prepared from the respective pyrido[2,3-d]pyrimidines 12b,d-g. Preliminary biological studies showed that 7-methyl and 5,7-dimethyl analogues (1b and 1e) were less active than methotrexate against human leukemic HL-60 and murine L-1210 cells in tissue culture. Compound 1e produced and ILS of 71% at 100 mg/kg per day x 5 (ip) in BDF mice inoculated ip with 106 L-1210 cells.