Some 2-substitution derivatives of 5-(4-oxo-6-hydroxy-3,4-dihydro-5-pyrimidinyl)pentanoic acid

1983 ◽  
Vol 48 (1) ◽  
pp. 304-311 ◽  
Author(s):  
Jiří Křepelka ◽  
Jan Beneš ◽  
Vladimír Pouzar ◽  
Jaroslav Vachek ◽  
Jiří Holubek
Keyword(s):  
Nitrile Group ◽  
Antineoplastic Activity ◽  
Carboxyl Group ◽  
Positional Isomers ◽  
Pentanoic Acid ◽  
Pharmacological Tests ◽  
Derivatives Of

Condensation of triethyl ester of 1,1,5-pentanetricarboxylic acid (XI) with substituted guanidines XXII - XXIX gave acids II - IX, which were converted into esters XI - XIX. The acid II and the ester XI were obtained as mixtures of positional isomers. Analogously, condensation of the triester XXI with dicyanodiamide gave rise to acid X, whose nitrile group, under conditions of esterification of a carboxyl group, produced iminoether XX. In pharmacological tests for antineoplastic activity the compounds prepared exhibited weaker efficacy than 5-(2-amino-6-hydroxy-4-oxo-3,4-dihydro-5-pyrimidinyl)pentanoic acid (I), employed as standard.

ÉTUDES SUR LA SYNTHÈSE DE L’HYDROXYPROLINE À PARTIR DE DÉRIVÉS DE L’ACIDE 2-AMINO-4-PENTÈNOÏQUE

1956 ◽  
Vol 34 (4) ◽  
pp. 502-514 ◽  
Author(s):  
Roger Gaudry ◽  
Louis Berlinguet ◽  
André Langis ◽  
Gérard Paris
Keyword(s):  
Double Bond ◽  
Acid Hydrolysis ◽  
Malonic Acid ◽  
Systematic Investigation ◽  
Carboxyl Group ◽  
Reaction Products ◽  
Pentanoic Acid ◽  
Copper Salts ◽  
Halogenation Reaction ◽  
Derivatives Of

A systematic investigation of the synthesis of 4-hydroxy-DL-proline and 2-amino-4-dihydroxyvaleric acid has been made, starting from the following derivatives of 2-amino-4-pentenoic acid: ethyl allylacetamidomalonate, ethyl allylacetamidocyanoacetate, 2-phthalimidopentenoic acid, allylacetamido-malonic acid, acetylallylglycine, 5-allylhydantoin, and 3-phenyl-5-allylhydantoin. Chlorine or bromine was added to the double bond of these compounds, and the reaction products were either derivatives of 5-halogenated-4-valerolactones or derivatives of 4,5-dihalogenated pentanoic acids, depending on whether the carboxyl group of the pentanoic acid was free or not when the halogenation reaction was carried out. Acid hydrolysis followed by treatment with barium hydroxide always gave mixtures, in different ratio, of 4-hydroxy-DL-proline and 2-amino-4,5-dihydroxyvaleric acid which were analyzed and isolated as the copper salts. In the case of 5-(2,3-dibromopropyl)hydantoin and 3-phenyl-5-(2,3-dibromopropyl)hydantoin, no cyclization could be obtained.

Some 2-substituted derivatives of 5-(2-amino-6-hydroxy-4-oxo-3,4-dihydro-5-pyrimidinyl)pentanoic acid

1981 ◽  
Vol 46 (6) ◽  
pp. 1397-1404 ◽  
Author(s):  
Rudolf Kotva ◽  
Jiří Křepelka ◽  
Antonín Černý ◽  
Vojtěch Pujman ◽  
Miroslav Semonský
Keyword(s):  
Point Of View ◽  
Pentanoic Acid ◽  
Antineoplastic Effect ◽  
Derivatives Of

On condensation of 6-substituted trialkyl esters of 2-carboxy-1,7-heptanedioic acids XIII-XXIII with guanidineand subsequent saponification 2-substituted 5-(2-amino-6-hydroxy-4-oxo-3,4-dihydro-5-pyrimidinyl)pentanoic acids II-XII were prepared. From the pharmacological point of view some of the substances prepared had a potentiating effect on the antileukemia effect of 5-fluorouracil in mice and the antineoplastic effect manifested by a diminution of the tumours in animals with experimental tumours.

2-Substituted derivatives of 5-(4-oxo-3,4-dihydro-5-pyrimidinyl)pentanoic acid

1982 ◽  
Vol 47 (9) ◽  
pp. 2525-2529 ◽  
Author(s):  
Rudolf Kotva ◽  
Jiří Křepelka ◽  
Jaroslav Vachek
Keyword(s):  
Pentanoic Acid ◽  
Antineoplastic Effect ◽  
Derivatives Of

Condensation of trialkyl esters of 6-substituted 2-carboxy-1,7-heptanedioic acids XII-XVII with urea or thiourea and subsequent saponification gave 2-substituted 5-(2,6-dihydroxy-4-oxo-3,4-dihydro-5-pyrimidinyl)pentanoic acids II-VI or 5-(2-mercapto-6-hydroxy-4-oxo-3,4-dihydro-6-pyrimidinyl)pentanoic acids VII-XI, respectively. Compounds II, VII and X had a weak antineoplastic effect in animals with experimental transplantable tumours.

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