Nucleoside, 391) Angular und linear erweiterte Allopurinole:Pyrazolo[4,3‐f]‐ und Pyrazolo[4,3‐g] chinazolinone

Ausgehend von 5-Aminoindazol (6)bzw. 5-Methyl-6-nitroindazol (17) wurden einfache, jeweils funfstufige Synthesen entwickelt fur 3,8-Dihydro-9H-pyrazolo[4,3-f]chinazolin-9-on (3), einem gewinkelten Benzologen von Allopurinol (1a), und fur die Pyrazolo [4,3-g]chinazolin-5-one 4, 29, 30 und 31, die gestreckt erweiterte Benzologe darstellen. 4 und 30 weisen eine dem Allopurinol vergleichbare Hemmung der Xanthin-Oxidase auf, wobei 4 unter Oxidation zum 7-Ox-Derivat 31 auch als Substrat fungiert. Nucleosides, 391) Angular and Linear Extended Allopurinols: Pyrazolo[4,3-f]- and Pyrazolo[4,3-g]quinazolinones Facile synthese have been developed for 3,8-dihydro-9H-pyrazolo[4,3-f]quinazolin-9-one (3), an angled benzolog of allopurinol (1a), and for the linear benzologously extended pyrazolo[4,3-g]-quinazolin-5-ones 4, 29, 30, and 31, involving five-step sequences starting with 5-aminoindazol (6) and 5-methyl-6-nitroindazol (17), respectively. 4 and 30 display a xanthine oxidase inhibition comparable to that of allopurinol, 4 also acting as a substrate, whereby it is oxidized to the 7-oxo derivative 31.

[1]  F. Lichtenthaler,et al.  Nucleosides, 381) The Ribonucleosides of Allopurinol , 1981 .

[2]  F. Lichtenthaler,et al.  Synthesis of a [3,4-f]-Linked Pyrazoloquinazolinone , 1981 .

[3]  A. Moser,et al.  Benzologs of allopurinol: Synthesis of pyrazolo [4,3-g] and [3,4-f] quinazolinones , 1980 .

[4]  N. Leonard,et al.  SYNTHESIS OF LIN-BENZOALLOPURINOL , 1979 .

[5]  R. Miller,et al.  Allopurinol ribonucleoside as an antileishmanial agent. Biological effects, metabolism, and enzymatic phosphorylation. , 1979, The Journal of biological chemistry.

[6]  N. Leonard,et al.  Synthesis of fluorescent nucleotide analogues: 5'-mono-, di-, and triphosphates of linear-benzoguanosine, linear-benzoinosine, and linear-benzoxanthosine. , 1979, Proceedings of the National Academy of Sciences of the United States of America.

[7]  N. Leonard,et al.  Synthesis of lin-benzoinosine, lin-benzoxanthosine, and lin-benzoguanosine , 1979 .

[8]  E. B. Skibo,et al.  Synthesis of fused [1,2,6]thiadiazine 1,1-dioxides as potential transition-state analogue inhibitors of xanthine oxidase and guanase. , 1979, Journal of medicinal chemistry.

[9]  D. Nelson,et al.  Metabolism of pyrazolo(3,4-d)pyrimidines in Leishmania braziliensis and Leishmania donovani. Allopurinol, oxipurinol, and 4-aminopyrazolo(3,4-d)pyrimidine. , 1979, The Journal of biological chemistry.

[10]  N. Kamatani,et al.  Suppression of cellular immunity due to inhibition of purine nucleoside phosphorylase by allopurinol-riboside. , 1979, Advances in experimental medicine and biology.

[11]  J. Barrio,et al.  Allosteric activation of aspartate transcarbamylase with a fluorescent nucleotide analogue: linear-benzo-ATP. , 1978, The Journal of biological chemistry.

[12]  J. Barrio,et al.  Dimensional probes of the enzyme binding sites of adenine nucleotides. Biological effects of widening the adenine ring by 2.4 A. , 1978, Biochemistry.

[13]  O. Uhlenbeck,et al.  Synthesis of modified nucleoside 3',5'-bisphosphates and their incorporation into oligoribonucleotides with T4 RNA ligase. , 1978, Biochemistry.

[14]  G. Elion.  Allopurinol and Other Inhibitors of Urate Synthesis , 1978 .

[15]  R. K. Robins,et al.  Chemistry and biology of nucleosides and nucleotides , 1978 .

[16]  T. Traut,et al.  Inhibitors of orotate phosphoribosyl-transferase and orotidine-5'-phosphate decarboxylase from mouse Ehrlich ascites cells: a procedure for analyzing the inhibition of a multi-enzyme complex. , 1977, Biochemical pharmacology.

[17]  N. Leonard,et al.  Linear benzoguanine. Synthesis by two independent methods , 1976 .

[18]  N. Leonard,et al.  Defined dimensional changes in enzyme substrates and cofactors. Synthesis of lin-benzoadenosine and enzymatic evaluation of derivatives of the benzopurines. , 1976, Journal of the American Chemical Society.

[19]  R. K. Robins,et al.  Synthesis and enzymic activity of some novel xanthine oxidase inhibitors. 3-Substituted 5,7-dihydroxypyrazolo(1,5-alpha)pyrimidines. , 1976, Journal of medicinal chemistry.

[20]  B. Lynch,et al.  Synthesis and biological evaluation of xanthine oxidase inhibitors. Pyrazolo(3,4-d)pyrimidines and pyrazolo(3,4-b)pyridines. , 1975, Journal of medicinal chemistry.

[21]  M. Sprecker,et al.  Linear benzoadenine. A stretched-out analog of adenine. , 1975, Journal of Organic Chemistry.

[22]  D. Nelson,et al.  Ribonucleotides of allopurinol and oxipurinol in rat tissues and their significance in purine metabolism. , 1974, Advances in experimental medicine and biology.

[23]  W. N. Kelley,et al.  Effects of allopurinol and oxipurinol on pyrimidine biosynthesis in man. , 1974, Advances in experimental medicine and biology.

[24]  R. Miller,et al.  Kinetic properties and inhibition of orotidine 5'-phosphate decarboxylase. Effects of some allopurinol metabolites on the enzyme. , 1973, The Journal of biological chemistry.

[25]  G. Hitchings,et al.  A comparison of the specificities of xanthine oxidase and aldehyde oxidase. , 1972, Archives of biochemistry and biophysics.

[26]  V. Massey,et al.  On the mechanism of inactivation of xanthine oxidase by allopurinol and other pyrazolo[3,4-d]pyrimidines. , 1970, The Journal of biological chemistry.

[27]  W. F. Wood,et al.  Irreversible enzyme inhibitors. CXXVI. Hydrocarbon interaction with xanthine oxidase by phenyl substituents on purines and pyrazolo[3,4-d]pyrimidines. , 1968, Journal of medicinal chemistry.

[28]  G. Hitchings,et al.  Effects of Xanthine Oxidase Inhibitors on Purine Catabolism , 1968 .

[29]  R. K. Robins.  ANTITUMOR ACTIVITY AND STRUCTURAL RELATIONSHIPS OF PURINE DERIVATIVES AND RELATED COMPOUNDS AGAINST NEOPLASMS IN EXPERIMENTAL ANIMALS. , 1964, Journal of medicinal chemistry.

[30]  R. K. Robins,et al.  Pyrazolopyrimidines as inhibitors and substrates of xanthine oxidase. , 1957, The Journal of biological chemistry.

[31]  R. Huisgen,et al.  Nitroso-acyl-amine und Diazo-ester IX Die Jacobsonsche Indazolsynthese und die Konfiguration der Diazo-ester , 1954 .

[32]  R. Huisgen.  Orientierungsphänomene bei der Substitution aromatischer Bicyclen II. Die Chinolinsynthese nach Combes , 1949 .

[33]  R. Huisgen.  Beiträge und Deutungsversuche zur Reaktionsweise aromatischer Bicyclen , 1948 .

[34]  W. Schäfer,et al.  Über die Darstellung von Phthalidabkömmlingen , 1929 .

[35]  T. Sandmeyer.  Über Isonitrosoacetanilide und deren Kondensation zu Isatinen , 1919 .

[36]  F. Kunckell.  Ueber einige Derivate des 2.4‐Diketotetrahydrochinazolins , 1905 .

[37]  E. Noelting.  Ueber Bildung von Indazolen aus nitrirten orthomethylirten Aminen , 1904 .

[38]  S. Niementowski.  Synthesen von Chinazolinverbindungen , 1894 .