88553-19-9Relevant academic research and scientific papers
Diastereoisomeric tetrahydropyrido-(2,3,d) pyrimidine derivatives
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, (2008/06/13)
The diastereoisomeric forms of N-(4-[2-(2-amino-4-hydroxy-5,6,7,8-tetrahydropyrido[2,3-d]-pyrimidin-6-yl)ethyl]benzoyl)-L-glutamic acid are antineoplastic agents. The compounds are prepared by separation of the diastereoisomeric form of the correspondingl
Pyrido(2,3-d)pyrimidine derivatives
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, (2008/06/13)
2,4-Diamino- and 2-amino-4-hydroxy- derivatives of N-(4-[1-(pyrido[2,3-d]pyrimidin-6-yl)alk-2-yl]-benzoyl)-L-glutamic acids, and the corresponding 5,6,7,8-tetrahydro compounds are antineoplastic agents. The compounds are prepared by hydrolytic or hydrogenolytic removal of carboxylic acid protecting groups from the correspondingly protected glutamic acid derivatives. A typical embodiment is N-(4-[2-(2-amino-4-hydroxy-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-6-yl)ethyl]benzoyl)-L-glutamic acid.
Synthesis of the Antileucemic Agents 5,10-Dideazaaminopterin and 5,10-Dideaza-5,6,7,8-tetrahydroaminopterin
Taylor, Edward C.,Harrington, Peter J.,Fletcher, Stephen R.,Beardsley, G. Peter,Moran, Richard, G.
, p. 914 - 921 (2007/10/02)
Total syntheses from pyridine precursors of 5,10-dideazaaminopterin (1) and 5,10-dideaza-5,6,7,8-tetrahydroaminopterin (2) are described.These compounds exhibit significant in vivo activity against L1210 leukemia that comparable to that observed with meth
Synthesis and Biological Activity of L-5-Deazafolic Acid and L-5-Deazaaminopterin: Synthetic Strategies to 5-Deazapteridines
Taylor, Edward C.,Palmer, David C.,George, Thomas J.,Fletcher, Stephen R.,Tseng, Chi Ping,et al.
, p. 4852 - 4860 (2007/10/02)
Condensation of 2,4-diamino-6(1H)-pyrimidinone with triformylmethane gives 6-formyl-5-deazapterin (13).Acetylation to 14, followed by reductive amination with dimethyl p-aminobenzoyl-L-glutamate and saponification of the resulting acetylated dimethyl ester 16 then gives L-5-deazafolic acid (12).Condensation of α-cyanothioacetamide with 2-methyl-3-ethoxyacrolein gives 3-cyano-5-methyl-2(1H)-pyridinethione (17), which is converted to 2--3-cyano-5-methylpyridine (18) by arylation with p-nitrofluorobenzene.Free-radical bromination of 18 to the 5-bromomethyl derivate, conversion to the corresponding aldehyde 21 by the Kroehnke procedure, formation of the acetal 22, and amination then gives 2-amino-3-cyano-5-(dimethoxymethyl)pyridine (23).This is condensed with guanidine and the product hydrolyzed selectively with formic acid to give 2,4-diamino-6-formyl-5-deazapteridine (26).Reductive amination of 26 with dimethyl p-aminobenzoyl-L-glutamate followed by saponification then gives L-5-deazaaminopterin (6).An alternative synthesis of 13 results from alkaline hydrolysis of 24 followed by acid cleavage of the resulting acetal 25.Two syntheses of 2,4-diamino-6-methyl-5-deazapteridine (32) are described; functionalization of the C-6 methyl group, however, was not possible.Syntheses of 3-formylthietane (45) and its dimethyl and ethylene acetals (44 and 46, respectively) are described, and their utilization as synthons for the pyridine ring in the 5-deazapteridines 51 and 52 is explored.Difficulties militating against this alternate strategy for the preparation of 26 are dicussed.L-5-Deazaaminopterin (6) is equipotent with methotrexate both as an inhibitor of bovine liver dihydrofolate reductase and of L1210 murine leukemia cells.It is also equipotent with methotrexate in vivo both against L1210 and P388 leukemia in BDF1 mice.
