5-Amino-1-methyl-1H-benzimidazole

The structure of the title compound, C8H9N3, a potential anti­tumour drug, was determined in order to give more insight into its structure–function relationships. The benzimidazole core of the mol­ecule was found to be exactly planar, while the substituents are displaced slightly from the mol­ecular plane [C—C—N—C and C—C—C—N torsion angles of 0.8 (3) and 179.0 (1)° for the methyl and amino groups, respectively]. The bond lengths are analysed in detail and compared with those of the parent unsubstituted analogues. The results show that the lone-pair electrons on the amino N atom are involved in conjugation with the adjacent π system and hence affect the charge distribution in the heterocycle. Two inter­molecular N—H⋯N and C—H⋯N hydrogen bonds have been identified

Dimethyl 2-(amino­methyl­ene)malonate

In the title compound, C6H9NO4, which is an example of a push–pull alkene, N—H⋯O inter­actions stabilize the crystal structure

Synthesis and Anticancer Activity of Novel 9-O-Substituted Berberine Derivatives

Berberine is a bioactive isoquinoline alkaloid derived from many plants. Although berberine has been shown to inhibit growth and induce apoptosis of several tumor cell lines, its poor absorption and moderate activity hamper its full therapeutic potential. Here, we describe the synthesis of a series of 9-O-substituted berberine derivatives with improved antiproliferative and apoptosis-inducing activities. An analysis of novel berberine derivatives by EPR spectroscopy confirmed their similar photosensitivity and analogous behavior upon UVA irradiation as berberine, supporting their potential to generate ROS. Improved antitumor activity of novel berberine derivatives was revealed by MTT assay, by flow cytometry and by detection of apoptotic DNA fragmentation and caspase-3 activation, respectively. We showed that novel berberine derivatives are potent inhibitors of growth of HeLa and HL-60 tumor cell lines with IC50 values ranging from 0.7 to 16.7 µM for HL-60 cells and 36 to >200 µM for HeLa cells after 48 h treatment. Further cell cycle analysis showed that the observed inhibition of growth of HL-60 cells treated with berberine derivatives was due to arresting these cells in the G2/M and S phases. Most strikingly, we found that berberine derivative 3 (9-(3-bromopropoxy)-10-methoxy-5,6-dihydro-[1,3]dioxolo[4,5-g]isoquino[3,2-a] isoquinolin-7-ylium bromide) possesses 30-fold superior antiproliferative activity with an IC50 value of 0.7 µM and 6-fold higher apoptosis-inducing activity in HL-60 leukemia cells compared to berberine. Therefore, further studies are merited of the antitumor activity in leukemia cells of this berberine derivative

Naturally occurring enolethers

Abstract Enolethers are a group of reactive compounds also occurring in the nature and displaying different kinds of activities, such as antifungal, antibacterial, nematocidal, cytostatic, cytotoxic, phytotoxic, nematicidal, antipyretic, hypotensive, analgesic, antitussive, depresant, anticancerogenic and antiviral

Mass Spectra of Some 4- and 5-Substituted Derivatives of Benzoselenadiazoles

Electron impact mass spectra of variety of eight 4-substituted and eight 5-substituted benzoselenadiazoles are presented and their spectral fragmentations are discussed. New mass spectra containing selenium in heterocyclic azole atom containing ring

Carbazol-9-yl-methanol

n/

Utilisation des alcoxyméthylènes disubstitués pour la synthèse d'hétérocycles d'intérêt biologique

L'objectif de ce travail a été l'application des alcoxyméthylènes disubstitués dans la synthèse des hétérocycles d'intérêt biologique.Les alcoxyméthylènes sont des éthers d'énol très réactifs,souvent utilisés comme précurseurs pour la synthèse de composés hétérocycliques de manière simple et efficace. La première partie de ce travail consiste en la synthèse de quinolones qui sont bien connus pour leurs activités antibactériennes. Ils sont habituellement préparés par la réaction de Gould-Jacobs. Il s'agit d'une réaction d'addition-élimination entre une amine aromatique et un alcoxymèthylène disubstitué (souvent l'éthoxyméthylènemalonate de diéthyle) suivie d'une cyclisation par voie thermique. La réaction de cyclisation par voie thermique est effectuée dans des solvants de hauts points d'ébullition (environ 250C), il reste toujours le problème d'isolement du produit après la réaction.C'est pourquoi nous avons étudié cette réaction dans des conditions de "chimie verte", c'est-à-dire en absence de solvant. Cette technique pourra être couplée dans certains cas avec une irradiation sous micro-ondes. Une seconde partie concerne la préparation de nouveaux composés alcoxyméthylèniques : le 2-éthoxyméthylène-3-oxobutanenitrile et le 3-éthoxy-2-méthanesulfonylacrylonitrile.Ces alcoxyméthylènes s'avèrent être un réactif particulièrement intéressant quant aux applications synthétiques possibles. De nouveaux hétérocycles (pyrazoles, pyrimidines et leurs dérivés) ont ainsi pu être préparés très simplement par réaction avec des amines particulières (hydrazines, amidines, aminotriazoles, aminobenzazoles).Les activités biologiques de quelques produits ainsi obtenus ont été testées.The aim of my PhD thesis was utilization of alkoxymethylene compounds in the synthesis of heterocycles possessing biological activity. The first part consists of solvent-free synthesis of quinolone derivatives. We have realised the synthesis of the quinolone derivatives in a three-step procedure from triethylorthoformate and activated methylene derivatives leading to alkoxymethylene malonates followed by reaction with aromatic amines and finally an intramolecular cyclization. High boiling solvents such as biphenyl and diphenyl ether used for thermal processes are solids at ambient temperature, which complicate work-up and recovery. To avoid this problem, a study of this reaction has been carried out under solvent-free conditions.The second part of my PhD study concerning the utilization of 2-ethoxymethylene-3-oxobutanenitrile and 3-ethoxy-2-methanesulfonylacrylonitrile in the synthesis of heterocycles possessing biological activity. As described in the literature, pyrazoles, pyrimidines and [1,2,4]triazolo[1,5-a]pyrimidines have been the subject of chemical and biological studies due to their interesting pharmacology including antipyretic, analgesic, antiinflammatory, potential herbicidal, fungicidal and leishmanicidal properties. Stimulated by these findings, the reactions of the titles compounds with hydrazines, amidines, aminotriazoles, aminobenzazoles and other nitrogen nucleophiles were studied giving access to a set of new substituted pyrazoles, pyrimidines, quinolines etc. Some of these products have been inspected for biological activities against bacteria, filamentous fungi, yeasts and tumor HeLa and L1210 cells.ORSAY-PARIS 11-BU Sciences (914712101) / SudocSudocFranceF