Rosowsky, Andre; Freisheim, James H.; Bader, Henry; Forsch, Ronald A.; Susten, Sandra A.; Cucchi, Carol A.; Frei, Emil III published an article in 1985, the title of the article was Methotrexate analogs. 25. Chemical and biological studies on the γ-tert-butyl esters of methotrexate and aminopterin.Synthetic Route of 53838-27-0 And the article contains the following content:
γ-tert-Bu aminopterin (I; R = R1 = H, R2 = CMe3) (II) was prepared, and new routes to the known γ-tert-Bu methotrexate (I; R = Me, R1 = H, R2 = CMe3) (III) were developed. Thus, pteridine IV (R3 = OH) was brominated by Br2/PPh3 to give IV (R3 = Br), which was treated in situ with p-H2NC6H4CO2H to give pteroic acid V (R = H), which was formylated to give V (R = CHO). The latter was condensed with H-Glu(OCMe3)-OMe.HCl by ClCO2CH2CHMe2 in DMF containing Et3N to give I (R = CHO, R1 = Me, R2 = CMe3), which was hydrolyzed and then deformylated to give II. II was also prepared by treating IV.HBr (R3 = Br) with p-RNHC6H4CO-Glu(OCMe3)-OR1 (VI, R = R1 = H) in AcNMe2 containing Me2CHNEt2. III was prepared by brominating IV (R3 = OH), treating the resulting IV (R3 = Br) with VI (R = R1 = Me), and hydrolyzing the resulting I (R = R1 Me, R2 = CMe3). The inhibitory effects of II on the activity of dihydrofolate reductase (DHFR) from L1210 murine leukemia cells, the growth of 4210 cells and CEM human leukemic lymphoblasts in suspension culture, and the growth of human squamous cell carcinoma of the head and neck in monolayer culture were compared with the effects of III and the parent acids aminopterin (I, R-R2 = H) and methotrexate (I, R = Me, R1 = R2 = H). The activity of II was close to that of III in the DHFR inhibition assay, but II was more potent than III against cells in culture and against L1210 leukemia in mice. The experimental process involved the reaction of (S)-5-tert-Butyl 1-methyl 2-aminopentanedioate(cas: 53838-27-0).Synthetic Route of 53838-27-0
The Article related to tertiary butyl ester aminopterin methotrexate, dihydrofolate reductase inhibitor aminopterin ester, leukemia inhibitor aminopterin methotrexate ester, Amino Acids, Peptides, and Proteins: Amino Acids and other aspects.Synthetic Route of 53838-27-0
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