- A convenient copper-catalyzed direct animation of nitroarenes with 9-alkylhydroxylamines
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O-Alkylhydroxylamines, particularly O-methylhydroxylamine, aminate nitroarenes in the presence of a strong base and a copper catalyst to give aminonitroarenes in good yields, ortho- or para-Animation with respect to the nitro group takes place, and in some cases the ortho-aminated product is preferentially obtained. With 3-substituted nitrobenzenes where the substituent has a lone pair of electrons, preferential amination occurs at the 2-position to give the sterically most congested 3c-f, 14 and 22g.
- Seko, Shinzo,Miyake, Kunihito,Kavvamura, Norio
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p. 1437 - 1444
(2007/10/03)
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- Hypoxia-Selective Agents Derived from Quinoxaline 1,4-Di-N-oxides
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Hypoxic cells, which are a common feature of solid tumors, but not normal tissues, are resistant to both anticancer drugs and radiation therapy.Thus the identification of drugs with selective toxicity toward hypoxic cells is an important objective in anticancer chemotherapy.The benzotriazine di-N-oxide (SR 4233, Tirapazamine) has been shown to be an efficient and selective cytotoxin for hypoxic cells.Since the bioreductive activation of Tirapazamine is thought to be due to the presence of the 1,4-di-N-oxide moiety, a series of 3-aminoquinoxaline-2-carbonitrile 1,4-di-N-oxides with a range of electron-donating and -withdrawing substituents in the 6- and /or 7- positions has been synthesized and evaluated for toxicity to hypoxic cells.Electrochemical studies of the quinoxaline di-N-oxides and Tirapazamine showed that as the electron-withdrawing nature of the 6(7)-substituent increases, the reduction potential becomes more positive and the compound is more readily reduced.Apart from the unsubstituted 6a and the 6,7-dimethyl derivative 6c, the quinoxaline di-N-oxide have reduction potentials significantly more positive than Tirapazamine (Epc -0.90 V).The most potent cytotoxins to cells in culture were the 6,7-dichloro and 6,7-difluoro derivatives 6i and 6l, which were 30-fold more potent than Tirapazamine.The 6(7)-fluoro and 6(7)-chloro compounds, 6e and 6h, showed the greatest hypoxia selectivity.Four of the compounds, 6e, 6f, 6h and 6i, killed the inner cells of multicellular tumor spheroids in vitro.In vivo Balb/c mice tolerated a dose of these four compounds twice the size of that of Tirapazamine.This study demonstrates that quinoxaline 1,4-di-N-oxides could provide useful hypoxia-selective therapeutic agents.
- Monge, Antonio,Palop, Juan A.,Cerain, Adela Lopez de,Senador, Virginia,Martinez-Crespo, Francisko J.,et al.
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p. 1786 - 1792
(2007/10/02)
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- 2-(Guanidino)-anilides and related compounds. Synthesis and anthelmintic activity. 3rd Communication: Anthelmintics
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Anilides bearing a guanidino, thioallophanato, isothioallophanato or amidino group in the ortho position were synthesized for investigations of their anthelmintic effects, and tested against sheep trichostrongylides. The most active anilides are those containing a 5-alkylthio, 5-alkylsulphinyl (alkyl = C3H7, C4H9), 5-phenylthio, 5-phenylsulphinyl or 4-phenylsulphonyloxy group, and a guanidino group substituted at both nitrogen atoms by a methoxycarbonyl group. The most active anthelmintic anilides are the form-, propion-, butyr- and methoxy-acetanilides. Of the guanidines unsubstituted at N' and N'', the 2-guanidino-5-phenylthio-2-methoxyacetanilide and the 2-guanidino-5-phenylsulphinyl-2-methoxyacetanilide were more active than parbendazole. From the class of bismethoxycarbonylguanidines, which are also the most interesting products in terms of stability, febantel (Rintal) has been introduced into veterinary practice for the treatment of nematode infections in horses, cattle, sheep and swine.
- Wollweber,Kolling,Niemers,et al.
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p. 531 - 542
(2007/10/02)
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- Process for the production of 2-aryl-2H-benzotriazoles
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A process for the production of 2-aryl-2H-benzotriazoles comprises reducing and cyclizing the corresponding o-nitroazobenzenes with hydrogen at a temperature in the range of about 20° C. to about 100° C. and at a pressure in the range of about 15 psia (1 atmosphere) to about 1000 psia (66 atmospheres) in an alkaline medium at a pH over 10 in the presence of a nickel catalyst, preferably molybdenum-promoted Raney nickel. High yields of pure product are obtained directly with a concomitant reduction of undesired by-product and a reduction in effluent pollution problems.
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- Process for the production of 2-aryl-2H-benzotriazoles
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A process for the production of 2-aryl-2H-benzotriazoles comprises reducing and cyclizing the corresponding o-nitroazobenzenes with hydrogen at a temperature in the range of about 20° C. to about 100° C. and at a pressure in the range of about 15 psia (1 atmosphere) to about 1000 psia (66 atmospheres) in an organic solvent mixture containing an organic amine at a pH over 10 in the presence of noble metal hydrogenation catalyst, preferably palladium. High yields of pure product are obtained with a concomitant reduction of undesired by-products and a reduction in effluent pollution problems.
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- Process for the production of 2-aryl-2H-benzotriazoles
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A process for the production of 2-aryl-2H-benzotriazoles comprises reducing and cyclizing the corresponding o-nitroazobenzenes with carbon monoxide at a temperature in the range of about 20° C. to about 150° C. and at a pressure in the range of about 15 psia (1 atmosphere) to about 1000 psia (66 atmospheres) in an alkaline medium at a pH over 10 in the presence of a copper-amine complex catalyst. High yields of pure product are obtained with a concomitant reduction of undesired by-products and a reduction in effluent pollution problems.
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- Process for the production of 2-aryl-2H-benzotriazoles
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An improved process for the production of 2-aryl-2H-benzotriazoles by the reduction of o-nitroazobenzene intermediates with zinc in alkaline medium comprises employing a ratio of moles of alkali to moles of o-nitroazobenzene intermediate in the range of 0.2-1.7/1 in the presence of less than 150 ppm of iron based on zinc used. The improved process results in higher yields of high purity products with a concomitant reduction in the amount of undesired cleavage amine by-products and a reduction in effluent pollution problems. The process is carried out in a polar/non-polar solvent mixture.
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