Showing papers by "Edward C. Taylor published in 1988"

Process for the preparation of fused pyridine compounds

Abstract: Pyrido[2,3-d]pyrimidine compounds are prepared through the reaction of 2,4-diamino-6(1H)-pyrimidone and an activated derivative of a dialdehyde. A typical embodiment utilizes the dinitrile.

Diastereoisomeric tetrahydropyrido-(2,3,d) pyrimidine derivatives

Abstract: 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 correspondingly protected glutamic derivatives and hydrolytic or hydrogenolytic removal of carboxylic acid and/or amino protecting groups. Typical embodiments are the (R,S) and (S,S) 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.

Studies on the molybdenum cofactor: model synthetic routes directed at Form B

Abstract: A general method for the conversion of available pyrazine intermediates to 6,7-dihydrothieno[2,3-b]pyrazines, and then to 6,7-dihydrothieno[3,2-g]pterins, has been developed as a model synthetic strategy for an approach to Form B of the molybdenum cofactor

6-alkenyl and ethynyl derivatives of 2-amino-4-hydroxypyrido[2,3-d]pyrimidines

Abstract: 2-Amino-4-hydroxy-6-[2-(4-carboxyphenyl)alk-1-en-1-yl]pyrido[2,3,-d]pyrimidines and 2-amino-4-hydroxy-6-[2-(4-carboxyphenyl)alk-1-yn-1-yl]pyrido[2,3-d]pyrimidines are prepared through the reaction of a halo-aromatic compound and an unsaturated compound in the prosence of a palladium catalyst. The products are chemical intermediates for the preparation of antineo-plastic agents. A typical embodiment is the reaction of a protected 2-amino-4-hydroxy-6-ethynylpyrido[2,3-d]pyrimidine and an ester of 4-iodobenzoic acid.

Diels-Alder reactions of 6-azapterins. An alternative strategy for the synthesis of 5,10-dideaza-5,6,7,8-tetrahydrofolic acid (DDATHF)

Abstract: Reaction de la N 2 -pivaloyl methylthio-7 aza-6pterine avec le pyrrolidino-4' butene-3' yl-4 benzoate de methyle; apres desulfuration sur nickel de Raney, obtention de N 2 -pivaloyl didesaza-5,10 pteroate de methyle

Diels-Alder reactions of 7-azalumazines: synthesis of condensed lumazines and 8-deazalumazines

Abstract: Addition intramoleculaire de Diels Alder de [tetrahydro-5,6,7,8 dimethyl-6,8 ω-alcynyloxy-3 ou ω-alcynylamino-3] pyrimido [4,5-e] triazine-1,2,4diones-6,8

Intramolecular Diels−Alder reactions of 6-azalumazines and 6-azapterins. A facile route to 6,7-annulated 5-deazapteridines

Abstract: Reaction des methylthio-7 aza-6lumazines et -pterines avec le pentyne-4ol-1, des butyne-3ols-1, l'hexyne-5ol-3 ou la butyne-3ylamine et cyclisation intramoleculaire des derives obtenus en furo-, pyranno- et pyrrolo [3,2-6,7] desaza-5pteridines

Synthesis of analogues of folic acid, aminopterin and methotrexate as antitumour agents.

Abstract: Publisher Summary This chapter discusses the syntheses of folic acid, aminopterin, and methotrexate analogs in which an intact L-glutamic acid side-chain is present while simultaneously varying the pteridine ring moiety, the C-9, N- 10 bridge and/or the benzoyl group. Several analogs of folic acid are known in which the only remaining structural feature of the folic acid molecule is the p-aminobenzoylglutamic acid moiety. Biological results are discussed in those cases where the analog has significant activity in tumor systems relative to methotrexate (MTX) or aminopterin (AP). Of the many classes of deazaFA derivatives investigated, none has received more attention or resulted in more promising candidate drugs than 5,8-dideaza (quinazoline) analogs. Methylation of folic acid (FA) with a 4-molar excess of methyl iodide gave a low yield of the tetramethyl derivative. A Dimroth rearrangement brought about by base at room temperature then gave hydrolysis of the methyl esters having taken place under the conditions of the rearrangement.

Synthesis of a novel tetrahydrothieno[2,3-b]pyrrole

Abstract: A partir d'[oxo-3 pyrrolidino]-4 benzoates d'alkyle et d'amide d'acide cyano thioacetique, synthese d'alcoxycarbonyl-4' phenyl-6 amino-2 cyano-3 tetrahydro-3a,4,5,6 thieno [2,3-b] pyrroles. Etude RX du derive alcoxy=t-butoxy

N-(4-(1-hydroxy-3-(5,6,7,8-tetrahydropyrido(2,3,-d)-pyrimidin-6-yl)prop-2-yl)benzoyl)glutamic acid derivatives

Abstract: N-[4-{1-Hydroxy-3-(2-amino-4-hydroxy-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-6-yl)prop-2-yl )benzoyl]-glutamic acid, it salts, and derivatives thereof, have an inhibitory effect on one or more enzymes which utilize folic acid and can be used, alone or in combination, to inhibit the growth of those neoplasms which otherwise depend upon the enzymes so inhibited. The compounds can be prepared through catalytic hydrogenation of a protected derivative of N-[4-{1-hydroxy-3-(2-amino-4-hydroxy-pyrido[2,3-d]pyrimidin-6-yl)prop-2-en-2-yl)benzoyl]glutamic acid and removal of the protecting groups.

Heterodienophilic Intramolecular Diels-Alder Reactions of 1,2,4-Triazines. Synthesis of Novel Polycyclic Condensed Pyrazines and Lumazines.

Abstract: - 3-(2'-Cyanophenoxy)-1,2,4-triazines and 7-(2'-cyanophenoxy)-6-azalumazines undergo intramolecular Diels-Alder reactions to yield novel polycyclic pyrazines and lumazines. However, the analogous 5-(2'-cyanophenoxy)-1,2,4-triazines fail to undergo cycloaddition, preventing access to the unknown benzfuro[2,3- e ]-1,2,4-triazine system. Substitution of oxime ethers for nitriles on the dienophilic sidechains of the respective Diels-Alder precursors failed to increase their inverse electron demand Diels-Alder reactivity.