Hassan A. Allimony

Synthesis of Heterobicyclic Nitrogen Systems Bearing a 1,2,4-Triazine Moiety as Anticancer Drugs: Part IV

Some new isolated and fused heterobicyclic nitrogen systems such as thiazolidinone, imidazolone, pyrimidinone, quinazolone, as-triazolone, as-triazinones, tetrazino-as-triazines, and the related compounds 3,4-diaminotriazine and sulfa derivatives 2–27 have been synthesized via treatment of 4-amino-6-styryl-3-thioxo-1,2,4-triazin-5(2,4H)ones (1) with cyclic and acyclic oxygen and nitrogen compounds. The structures of the products have been established from their elemental and spectral analyses. Some new compounds exhibited significant anticancer activities, where compounds 11j > 2a > 6 and 11I > 14 > 11k showed a moderate activity toward leukemia, ovarian cancer, and non-small cell lung cancer. The authors are very grateful to Prof. Dr. Johan P. Bader, Chief Antiviral Evaluations Branch and Prof. Dr. V. L. Narayanan, Chief Drug Synthesis, Chemistry Branch National Cancer Institute, Bethesda, Maryland, USA for evalution of the vitro antitumor tests as development program. Thanks also are due to the members of the NCl staff.

Synthesis, chemical reactivity and fungicidal activity of pyrido[1,2-b][1,2,4]triazine derivatives

The synthesis of some new pyrido[1,2-b][1,2,4]triazines (2-12) was achieved by cyclocondensation of 4-aryl-1,6-diamino-2-oxo-1,2-dihydropyridine-3,5-dicarbonitriles (1a, b) with α,β-bifunctional compounds. Pyrido[1,2:2´,3´]triazino[5´,6´-f]triazines (13-14) were also prepared. The behavior of 1a, b toward interactions with indole-2,3-dione and its N-acetyl analogue have been studied under different reaction conditions. The structures of the new products have been deduced from elemental analysis and spectral data (UV, IR, 1H NMR, 13C NMR and mass spectra). The new synthesized compounds were screened for their antifungal activities.

FUSED CYANOPYRIMIDINES: PART II SYNTHESIS AND REACTIONS OF FUSED CYANOPYRIMIDINE DERIVATIVES AS AFFECTING ENZYMATIC AGENTS

Abstract Some new fused heterobicyclic systems, such as thiazolo[3,2-a]-pyrimidin-5-one (3), 2,3-tetrahydrothiazolo[3,2-a]pyrimidin-5-one (5), 2,4-tetrahydrothiazino[3,2-a]pyrimidin-3,6-dione (6), 3-dihydrothiazino[3,2-a]pyrimidin-2,4,6-trione (7), 3-arylidenethiazino[3,2-a]pyrimidin-2,4,6-trione (8) and/or the related nitrogen compounds, such as 2,3-tetrahydroimidazolo[3,2-a]-pyrimidin-5-one (9), 1-aryl-2,3-tetra-hydroimidazolo[3,2-a]pyrimidin-5-one (11), quinazolino[3,2-a]-pyrimidin-6,8-dione (12) and 3-mercapto-1,2,4-triazolo[4,3-a]pyrimidin-5-one (14) have been synthesized by the interaction of 2-mercapto-4-arylidene-5-cyanopyrimidin-6(1H)one (1) with α,β-bifunctional nitrogen, oxygen and/or sulfur compounds. The structures have been characterized by elemental analyses, IR, UV, 1H NMR and mass spectral data. Some newly prepared compounds revealed a moderate effect on the activity of cellobiase produced by Aspergillus nidulans.

Substituted quinolinones 27.* Regioselective synthesis of pyrazolo-, oxazolo-, and triazepinoquinoline derivatives

Reactivity of 3-acetyl-4-(methylsulfanyl)quinolin-2(1H)-one towards 1,2- and/or 1,4-diazanucleophiles has been studied under different reaction conditions. Condensation of 3-acetyl-4-(methylsulfanyl)quinolin-2(1H)-one with hydrazine, phenylhydrazine, hydroxylamine hydrochloride, semicarbazide, and thiosemicarbazide was carried out in different media. The structure of the reaction products was dependent not only on the reagent used, but also on the solvent and reaction temperature. Accordingly, the reaction regioselectively produced in good yields pyrazolo[3,4-b]quinoline, pyrazolo[4,3-c]quinoline, oxazolo[5,4-b]quinoline, oxazolo[4,5-c]quinoline, isoxazolo-[4,5-c]quinoline, [1, 2, 4]triazepino[5,6-b]quinoline, and [1,2,4]triazepino[6,5-c]quinoline derivatives in addition to open-chain condensates which, too, were transformed to the respective cyclic products. The structures of new products were established on basis of their analytical and spectral data.

Substituted Quinolinones. Part 19. New and Unexpected Results from Oxidation of 3-Acetyl-1-Alkyl- 4-Hydroxyquinolin-2(1H)-Ones Using Selenium Dioxide

Abstract Oxidation of 3-acetyl-1-alkyl-4-hydroxyquinolin-2(1H)-ones using selenium dioxide under Riley conditions was described. The oxidation reaction produced a mixture of 2 unexpected α-keto acid and its dehydrated dimer derivatives. The oxidation reaction was studied under different reaction conditions in order to maximize the yields and optimize reaction conditions. Also, 1-alkyl-4-hydroxy-3-(2-nitroacetyl)quinolin-2(1H)-one and/or 3-acetyl-1-alkyl-4-diflouro-boryloxyquinolin-2(1H)-one derivatives were subjected to the same oxidation reaction giving rise improved reaction yields and selectivity in case of the boron-complex. Alkaline degradation of the dehydrated dimers led to formation of the 4-hydroxy-2-oxoquinoline-3-carboxylic acids while under the same conditions the α-keto acids underwent deoxalylation. [Supplemental materials are available for this article. Go to the publishers online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the following free supplemental files: Additional figures]. GRAPHICAL ABSTRACT