- An N1-hydrogen bonding model for flavin coenzyme
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A model flavin possessing a specific hydrogen bond to the N1-position has been synthesized. The redox potential has been measured in aqueous buffer and found to be shifted +21 mV as compared to a similar flavin lacking this hydrogen bond. The reaction of the N1-hydrogen-bonding model with sulfite and 1-benzyl-dihydronicotinamide were examined and compared with the non-hydrogen-bonded flavin. The N1-hydrogen bond did not accelerate the rate of sulfite ion or hydride addition to N5, however the N5-sulfite complex was stabilized by nearly 4-fold over a non-hydrogen-bonding model. The model flavins were also studied computationally.
- Guo, Fengli,Chang, Bryan H.,Rizzo, Carmelo J.
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- Approach to the synthesis of 8-nitroquinoline-2-carboxylic acid in high yield
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A synthesis of 8-nitroquinoline-2-carboxylic acid was optimized, using the following basic scheme of transformations: 1) nitration of 2-methylquinoline with subsequent separation of a mixture of isomeric 8-nitroand 5-nitro-2-methylquinolines; 2) oxidation of the methyl group in 2-methyl-8-nitroquinoline (including consecutive steps of bromination and hydrolysis in aqueous sulfuric acid). A new method for the separation of isomeric 8-nitroand 5-nitro-2methylquinolines was suggested. The optimal conditions for the final step of hydrolysis were selected, which gave almost quantitative yield of 8-nitroquinoline-2-carboxylic acid.
- Gadomsky, S. Ya.,Yakuschenko
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p. 816 - 818
(2016/12/27)
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- Discovery of a new antileishmanial hit in 8-nitroquinoline series
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A series of nitrated 2-substituted-quinolines was synthesized and evaluated in vitro toward Leishmania donovani promastigotes. In parallel, the in vitro cytotoxicity of these molecules was assessed on the murine J774 and human HepG2 cell lines. Thus, a very promising antileishmanial hit molecule was identified (compound 21), displaying an IC50 value of 6.6 μM and CC 50 values ≥ 100 μM, conferring quite good selectivity index to this molecule, in comparison with 3 drug-compounds of reference (amphotericin B, miltefosine and pentamidine). Compound 21 also appears as an efficient in vitro antileishmanial molecule against both Leishmania infantum promastigotes and the intracellular L. donovani amastigotes (respective IC50 = 7.6 and 6.5 μM). Moreover, hit quinoline 21 does not show neither significant antiplasmodial nor antitoxoplasmic in vitro activity and though, presents a selective antileishmanial activity. Finally, a structure-activity relationships study enabled to define precisely the antileishmanial pharmacophore based on this nitroquinoline scaffold: 2-hydroxy-8-nitroquinoline.
- Paloque, Lucie,Verhaeghe, Pierre,Casanova, Magali,Castera-Ducros, Caroline,Dumetre, Aurelien,Mbatchi, Litaty,Hutter, Sebastien,Kraiem-M'Rabet, Manel,Laget, Michele,Remusat, Vincent,Rault, Sylvain,Rathelot, Pascal,Azas, Nadine,Vanelle, Patrice
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- Carbapenem antibiotic compounds
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The present invention relates to carbapenems and provides a compound of the formula (I) STR1 wherein: R1 is 1-hydroxyethyl, 1-fluoroethyl or hydroxymethyl; R2 is hydrogen or C1-4 alkyl; R3 is hydrogen or C1-4 alkyl; P1 is of the formula: STR2 and one or two of A,B,C,D,E,F,G and H, are nitrogen and the remainder are CH; and P is bonded to the nitrogen of the linking carbamoyl group by a carbon atom, in either ring, is substituted by the carboxy group on a carbon atom, in either ring, and is optionally further substituted, by up to three substitutents, on a carbon atom, in either ring; or a pharmaceutically acceptable salt or in vivo hydrolysable ester thereof. Processes for their preparation, intermediates in their preparation, their use as therapeutic agents and pharmaceutical compositions containing them are also described.
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