- Nitric Oxide Releasing Prodrugs of Therapeutic Agents
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The present invention relates to nitric oxide releasing prodrugs of known drugs or therapeutic agents which are represented herein as compounds of formula (I) wherein the drugs or therapeutic agents contain one or more functional groups independently sele
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Page/Page column 82
(2011/11/06)
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- Chemical insights in the concept of hybrid drugs: The antitumor effect of nitric oxide-donating aspirin involves a quinone methide but not nitric oxide nor aspirin
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Hybrid drug 1 (NO-ASA) continues to attract intense research from chemists and biologists alike. It consists of ASA and a -ONO2 group connected through a spacer and is in preclinical development as an antitumor drug. We report that, contrary to current beliefs, neither ASA nor NO contributes to this antitumor effect. Rather, an unsubstituted QM was identified as the sole cytotoxic agent. QM forms from 1 after carboxylic ester hydrolysis and, in accordance with the HSAB theory, selectively reacts with cellular GSH, which in turn triggers cell death. Remarkably, a derivative lacking ASA and the -ONO 2 group is 10 times more effective than 1. Thus, our data provide a conclusive molecular mechanism for the antitumor activity of 1. Equally importantly, we show for the first time that a "presumed invisible" linker in a hybrid drug is not so invisible after all and is in fact solely responsible for the biological effect.
- Hulsman, Niels,Medema, Jan Paul,Bos, Carina,Jongejan, Aldo,Leurs, Rob,Smit, Martine J.,De Esch, Iwan J. P.,Richel, Dick,Wijtmans, Maikel
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p. 2424 - 2431
(2008/02/03)
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- Nitroderivatives as drugs for diseases having an inflammatory basis
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Use for the treatment of diseases having an inflammatory basis of compounds or salts thereof, having the following general formula (I): A-Xt-L-(W)p—NO2 wherein A contains the radical of a drug, Xt and W arc bivalent radicals, L, is a covalent bond or oxygen, sulphur, NRtc wherein Rtc is H or a C1-C5 linear or branched alkyl.
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- Process for obtaining (nitroxymethyl)phenyl esters of salicylic acid derivatives
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A process for obtaining (nitroxymethyl)phenyl esters of salicylic acid derivatives of formula (I) wherein R1is the OCOR3group characterized in that it comprises the following steps: a) reaction of a halide of a salicylic acid derivative with hydroxybenzylacohol in the presence of a base: b) nutration of the obtained product in anhydrous conditions by a mixture of nitric acid with a different inorganic acid, or an organic acid, or an anhydride of one or two organic acids: c) recovery of the final product.
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Page column 5
(2008/06/13)
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- Nitric oxide-donating non-steroidal anti-inflammatory drugs: The case of nitroderivatives of aspirin
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Nitric oxide (NO) acts as a key signalling mechanism in a number of cells and tissues in the mammalian organism. Modulation of the biosynthesis of NO has emerged to be relevant to the treatment of a variety of human diseases. In the attempt to reduce the serious side effects of non-steroidal anti-inflammatory drugs (NSAIDs), especially in the gastrointestinal tract, a NO-releasing moiety has been linked to conventional NSAIDs. A prototypical example is that of NO-releasing derivatives of aspirin. Thanks to the cytoprotective action of NO such compounds do not produce gastric damage and are emerging as an interesting novel group of drugs for their unique pharmacological properties.
- Chiroli, Valerio,Benedini, Francesca,Ongini, Ennio,Del Soldato, Piero
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p. 441 - 446
(2007/10/03)
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- Prodrugs - Part 1. Formylphenyl esters of aspirin
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The synthesis and study of a novel series of potential prodrugs of aspirin is reported. 2-, 3- and 4-formylphenyl aspirins, as well as a series of 4-substituted 2-formylphenyl aspirins, have been prepared. A study of their alkaline hydrolysis indicates that these compounds act as true prodrugs of aspirin which hydrolyse to aspirin and the formylphenol. The rates of hydrolysis and activation parameters indicate that hydrolysis of the 2-formylphenyl esters employs an intramolecular catalytic route.
- Bowden,Huntington,Powell
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p. 987 - 993
(2007/10/03)
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