- Synthesis of Functionalized Pyridines via a Regioselective Oxazoline Promoted C-H Amidation Reaction
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The first Rh-catalyzed C-H amidation of pyridines is reported. The incorporation of a substituent at the C2 position both is crucial to the success of this transformation and provides considerable scope for further elaboration of the resulting products. Among these compounds, 2-chloropyridines allow access to a selection of intermediates including a versatile azaquinazoline scaffold.
- Maiden, Tracy M. M.,Swanson, Stephen,Procopiou, Panayiotis A.,Harrity, Joseph P. A.
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supporting information
p. 3434 - 3437
(2016/07/26)
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- Synthesis, antinociceptive activity and pharmacokinetic profiles of nicorandil and its isomers
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Nicorandil (N-(2-hydroxyethyl)nicotinamide nitrate) is an antianginal drug, which activates guanylyl cyclase and opens the ATP-dependent K+ channels, actions that have been suggested to mediate its vasodilator activity. We synthesized nicorandil and its two isomers, which vary in the positions of the side chain containing the nitric oxide (NO) donor, and also their corresponding denitrated metabolites. The activities of these compounds were evaluated in an experimental model of pain in mice. Pharmacokinetic parameters of nicorandil and its isomers, as well as the plasma concentrations of the corresponding denitrated metabolites and also nicotinamide and nitrite were determined. Nicorandil exhibited the highest antinociceptive activity, while the ortho-isomer was the least active. Nicorandil and para-nicorandil, which induced higher plasma concentrations of nitrite, exhibited higher antinociceptive activity, which suggests that the release of NO may mediate this activity.
- Cesar, Isabela C.,Godin, Adriana M.,Araujo, Debora P.,Oliveira, Francinely C.,Menezes, Raquel R.,Santos, Julliana R.A.,Almeida, Mariana O.,Dutra, Marcela M.G.B.,Santos, Daniel A.,MacHado, Renes R.,Pianetti, Gerson A.,Coelho, Marcio M.,De Fatima, Angelo
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p. 2783 - 2790
(2014/05/06)
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- Study of synthesis and cardiovascular activity of some furoxan derivatives as potential NO-donors
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A series of hybrid molecules incorporating the furoxan and nicorandil moieties were designed as potential NO donors with cardiovascular and cerebrovascular activities. Thirty-six target molecules were successfully synthesized by conventional methods and characterized by infrared spectroscopy, 1H-NMR spectroscopy and high resolution mass spectra. The compounds were tested for their effects on KCl-induced contraction of rabbit thoracic aorta whose endothelium was denuded. Eight compounds were found to reduce KCl-induced contraction by more than 30% at 10 μM. All except one of these compounds are characterized by the presence of electron withdrawing groups in the phenyl ring attached via an amide or ester linkage to the furoxan moiety. The nature of the terminal carbonyl linkage (ester or amide) and the length or type of the alkyl chain bridging the two carbonyl functions have little effect on the activity. One of the active compounds, N-(4- methoxy-benzoyl)-N'-[3-methylfuroxanyl-4-carbonyl)piperazine (17i) was tested for hypotensive effects on anaesthetized rats at 1.5 mg/kg, and found to demonstrate a gradual and sustained hypotensive effect. The results suggest that the furoxannicorandil derivatives are a useful lead in the design of NO- donor compounds for hypertension.
- Mu, Li,Feng, Si-Shen,Go, Mei Lin
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p. 808 - 816
(2007/10/03)
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- Reactions of Hydroxy Carboxylic Acid Amides and Their O-Trimethylsilyl Derivatives with Chloro(chloromethyl)-dimethylsilane. Synthesis of 1-Oxa-4-aza-2-sila-and 1-Oxa-4-aza-2,6-disilacyclohexanes
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A general strategy has been developed for the synthesis of 1-oxa-4-aza-2-silacyclohexanes, 1-oxa-4-aza-2-silacyclohexan-5-ones, and 4-acyl-1-oxa-4-aza-2-silacyclohexanes from carboxylic acid amides containing a hydroxy group in the acid and/or amide moiety via two routes. The first of these includes transformation of N-monosubstituted carboxamides into corresponding O-trimethylsilyl derivatives which react with chloro(chloromethyl)dimethylsilane in the presence of a base to form unstable N-chlorodimethylsilyl-methyl amide derivatives with a five-coordinate silicon atom. Thermal decomposition of the latter during fractionation yields the target silicon-containing heterocycles with an OSiCH2N fragment. The second route consists of direct treatment of N-monosubstituted carboxamides with a mixture of hexamethyldisilazane and chloro(chloromethyl)dimethylsilane, which results in formation of 1-oxa-4-aza-2-silacyclohexan-5-ones and 4-acyl-1-oxa-4-aza-2-silacyclohexanes in high yields, thus excluding preliminary O-silylation of the starting hydroxy amides. One-pot reactions of N-unsubstituted carboxylic acid amides with a hexamethyldisilazane-chloro(chloromethyl)dimethylsilane mixture, followed by hydrolysis, yield 4-acyl-1-oxa-4-aza-2,6-disilacyclohexanes.
- Baukov,Shipov,Kramarova,Mamaeva,Zamyshlyaeva,Anisimova,Negrebetskii
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p. 1216 - 1228
(2007/10/03)
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- Use of N-acyl derivatives of aminoalcohols for the manufacture of a medicament for the treatment of pathologies involving mast cells
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N-acyl-derivatives of amino alcohols suitable for the therapeutic treatment of pathologies characterized by degranulation of mast cells caused by a neurogen and/or immunogenic hyperstimulation.
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