Copper-Catalyzed Arylation Reaction in the Synthesis of New Derivatives of Angular Triazaphenoxazinone

The synthesis of 11-(N-substituted)-angular triazaphenoxazinone via copper catalyzed N-arylation reaction is reported. The key intermediate, 7-chloro-5, 8-quinolinequinone was obtained in a five-step reaction, starting from 8-hydroxyquinoline. This was coupled with 4, 5-diamino-6-hydroxypyrimidine, in the presence of sodium acetate under anhydrous condition to afford 11-amino-1, 8, 10-triazabenzo[a]phenoxazin-5-one. The new derivatives were obtained by the reaction of 11-amino-1, 8, 10-triazabenzo[a]phenoxazin-5-one with substituted potassium/lithium phenyltriolborates, under the catalytic influence of copper (II) acetate in the presence of trimethylamine N-oxide, and 4Å molecular sieve. Products were obtained in good yield (70-80%). Structures were established by spectra and analytical data. These tetracyclic heterocycles absorb light in the visible region (400-700nm), which makes them applicable as laser dyes. Keywords: synthesis, triazaphenoxazinone, copper catalyzed N-arylation reactio

Copper Catalysed N-Arylation of Angular Triazaphenothiazinone

The copper catalyzed N-arylation of angular aminotriazaphenothiazinone is reported. This was achieved by the coupling of 11-amino-1,8,10-triazabenzo[a]phenothiazin-5-one with potassium or lithium aryltriolborate in the presence of a copper catalyst  for over 20h at room temperature to give the desired product. The success of this reaction lies in the preparation of the key intermediate, 11-amino-1, 8, 10-triazabenzo[a]phenothiazin-5-one synthesized by the condensation of 4, 5-diamino-6-thioprimidine with 7-chloro-5, 8-quinolinequinone in an anhydrous basic medium. Structures were assigned on the basis of spectral and analytical data.   Keywords: Aminotriazaphenothiazinone, triazabenzo[a]phenothiazinone, aryltriolborate, diaminothioprimidine

New carboxamide derivatives bearing benzenesulphonamide as a selective COX-II inhibitor: Design, synthesis and structure-activity relationship.

Sixteen new carboxamide derivatives bearing substituted benzenesulphonamide moiety (7a-p) were synthesized by boric acid mediated amidation of appropriate benzenesulphonamide with 2-amino-4-picoline and tested for anti-inflammatory activity. One compound 7c showed more potent anti-inflammatory activity than celecoxib at 3 h in carrageenan-induced rat paw edema bioassay. Compounds 7g and 7k also showed good anti-inflammatory activity comparable to celecoxib. Compound 7c appeared selectivity index (COX-2/COX-1) better than celecoxib. Compound 7k appeared selectivity index (COX-2/COX-1) a little higher than the half of celecoxib while compound 7g is non-selective for COX-2. The LD50 of compounds 7c, 7g and 7k were comparable to celecoxib

Synthesis, characterization and in vitro antitrypanosomal activities of new carboxamides bearing quinoline moiety.

The reported toxicities of current antitrypanosomal drugs and the emergence of drug resistant trypanosomes underscore the need for the development of new antitrypanosomal agents. We report herein the synthesis and antitrypanosomal activity of 24 new amide derivatives of 3-aminoquinoline, bearing substituted benzenesulphonamide. Nine of the new derivatives showed comparable antitrypanosomal activities at IC50 range of 1-6 nM (melarsoprol 5 nM). Compound 11n and 11v are more promising antitrypanosomal agents with IC50 1.0 nM than the rest of the reported derivatives. The novel compounds showed satisfactory predicted physico-chemical properties including oral bioavailability, permeability and transport properties

New antibacterial, antifungal and antioxidant agents bearing sulfonamide

The successful nickel catalyzed synthesis of N-(aryl) substituted p-toluene sulphonamides is reported. The intermediate 4-methylbenzenesulphonamide was obtained by the reaction of p-toluenesulphonyl chloride and ammonium hydroxide. Substituted p-toluene sulphonamides were obtained by coupling 4-methylbenzenesulphonamide with readily available aryl halides via Buchwald-Hartwig cross-coupling reaction. The structures of the compounds were confirmed using Fourier Transform Infrared (FT-IR), proton NMR, carbon-13 NMR and mass spectroscopy. The new compounds were screened for antibacterial and antifungal activities against Bacillus subtilis, Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Candida albicans and Aspergillus niger using agar diffusion technique. Some of the compounds showed improved antimicrobial activity when compared with ciprofloxacin and ketoconazole. The sulphonamides were further screened for antioxidant activity using 1,1-diphenyl-2-picrylhydrazide (DPPH), ferric reducing antioxidant potency (FRAP) and ferrous sulphate induced lipid peroxidation. The compounds showed improved antioxidant activity on comparison with ascorbic acid. Specifically, compound 20 was revealed by this study to be a lead antibacterial and antifungal agent whereas compound 17 showed a lead as antioxidant agent. The drug-likeness study indicated that none of the compounds violated Lipinski, Ghose, and Verber rules for drug-able molecules

<i>In vitro</i> anti-inflammatory activity.

<p><i>In vitro</i> anti-inflammatory activity.</p

Description of <i>p</i>-toluenesulphonamide derivatives 7i-n.

<p>A structural representation of the <i>p</i>-toluenesulphonamide derivatives 7i-n and the intermediates 3i-n and 5i-n.</p

Description of <i>p</i>-nitrobenzenesulphonamide derivatives 7a-f.

<p>A structural representation of the <i>p</i>-nitrobenzenesulphonamide derivatives 7a-f and the intermediates 3a-f and 5a-f.</p