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.

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.

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

1986 ◽  
Vol 51 (5) ◽  
pp. 1140-1149 ◽  
Author(s):  
Jiří Křepelka ◽  
Antonín Černý ◽  
Rudolf Kotva ◽  
Jaroslav Vachek ◽  
Milan Mělka
Keyword(s):  
Free Acid ◽  
Guanidine Hydrochloride ◽  
Amino Acid Esters ◽  
Pentanoic Acid ◽  
Urea Derivative ◽  
Sodium Ethylate ◽  
Chloride Method ◽  
Derivatives Of ◽  
Tumour Activity ◽  
Acid Esters

Using the chloride method esters II - X, amides XI - XIV, and condensates with amino acid esters XV - XVII were prepared from 5-(2-amino-6-hydroxy-4-oxo-3,4-dihydro-5-pyrimidinyl)pentanoic acid (I); the amides XIII and XIV were also prepared by aminolysis of ester II. The derivative of glycine, XVIII, was obtained on saponification of ester XV, also obtained by condensation of triethyl ester of N-(6,6-dicarboxyhexanol)glycine (XXIII) with guanidine hydrochloride in a medium containing sodium ethylate. Hydrazinolysis of ethyl ester XXIV gave hydrazine XIX. Disubstituted ureas XX - XXI were obtained on reaction of esters VI and XXIV with 2-chloroethyl isocyanate; saponification of the ester function in the urea derivative XX led to the free acid XXII. Reaction of acid I with an excess of diazomethane gave a mixture of compounds in which compound XXV (a product of esterification and O-methylation) and XXVI( a product of esterification, O-methylation, and N-methylation) predominated. None of the substances prepared displayed a clear ant-tumour activity. Some of the substances tested affected the weight of experimental tumours (XV, XVI, XX, XXV) or protracted the survival time of experimental animals (XXVI, XX). Substance XX had the broadest spectrum of activity.

Some ω-(2-amino-6-hydroxy-4-oxo-3,4-dihydro-5-pyrimidinyl) alkanoic acids, their derivatives and analogues

1980 ◽  
Vol 45 (12) ◽  
pp. 3583-3592 ◽  
Author(s):  
Miroslav Semonský ◽  
Antonín Černý ◽  
Jiří Křepelka ◽  
Rudolf Kotva ◽  
Bohumil Kakáč ◽  
...  
Keyword(s):  
Ethyl Ester ◽  
Spectral Methods ◽  
Barbituric Acid ◽  
Thiobarbituric Acid ◽  
Point Of View ◽  
Antineoplastic Effect ◽  
Alkanoic Acids ◽  
Derivatives Of ◽  
Acyl Derivatives

Condensation of 1,1,ω-alkanetricarboxylic acids triethyl esters XIV-XXI with guanidine gave ω-(2-amino-6-hydroxy-4-oxo-3,4-dihydro-5-pyrimidinyl) alkanoic acids I-IV, VI-VIII, XIII of which some were converted to derivatives (ethyl ester V, N-acyl derivatives XI and XII). Similarly, triester XVII gave by condensation with urea or thiourea the analogous 5-substituted derivatives of barbituric acid X, and thiobarbituric acid IX, respectively. The structures of selected compounds of this group (IV, V, IX-XI and XIII) were determined by spectral methods. Of interest, from the pharmacological point of view, has proved compound IV, which exhibited a significant antineoplastic effect on some experimental tumours in mice and rats, and enhanced the action of some current cytostatics.

Derivatives of 4-aryl-2,3-dihalogeno-1-naphthol

1980 ◽  
Vol 45 (10) ◽  
pp. 2700-2705 ◽  
Author(s):  
Jiří Křepelka ◽  
Viktor Zikán ◽  
Jiří Holubek ◽  
Miroslav Semonský
Keyword(s):  
Intramolecular Cyclization ◽  
Zinc Chloride ◽  
Antineoplastic Effect ◽  
Methyl Derivatives ◽  
Derivatives Of

Using intramolecular cyclization of the in situ prepared chlorides of acids XVI-XX, catalysed with zinc chloride, corresponding 4-aryl-2,3-dihalogeno-1-naphthols III-VII were prepared. Methylation or acetylation of compounds I, IV-VI gave O-methyl-derivatives VIII-XI or O-acetyl derivatives IXII-XV, respectively. Compounds III-XV displayed a weak antineoplastic effect in animals with some transplantable tumours.

Some derivatives of 4-aryl-2,3-dicyano-1-naphthol

1981 ◽  
Vol 46 (6) ◽  
pp. 1523-1529 ◽  
Author(s):  
Jiří Křepelka ◽  
Iva Vančurová ◽  
Jiří Holubek
Keyword(s):  
Spectral Methods ◽  
Aluminium Chloride ◽  
Partial Substitution ◽  
Anhydrous Aluminium Chloride ◽  
Antineoplastic Effect ◽  
Derivatives Of

Reactions of vicinal aromatic dibromo derivatives Ia-d with the system copper(I) cyanide-tetramethylurea gave the vicinal dicyano derivatives IIa-d; products of partial substitution, Va-d, demethylation and deacetylation, IIIa-c, were also formed. The compounds IIIa-c were also prepared by direct demethylation of compounds IIa-c with the system anhydrous aluminium chloride-dichloroethane. The structures of selected compounds were determined by spectral methods. Compounds IIa-d have proved to have a moderate antineoplastic effect in animals with some transplantable experimental tumours.

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