- Metal-Free Approach to Zolpidem, Alpidem and their Analogues via Amination of Dibromoalkenes Derived from Imidazopyridine and Imidazothiazole
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A novel efficient approach towards Zolpidem, Alpidem and their analogues was elaborated. The corresponding amides derived from imidazopyridine and imidazothiazole were prepared by the reaction of amines with previously unknown dibromoalkenes having these heterocyclic fragments. Amination of dibromoalkenes in the presence of water led directly to target drugs and their analogues in up to 95 % yield.
- Muzalevskiy, Vasiliy M.,Sizova, Zoia A.,Shastin, Alexey V.,Nenajdenko, Valentine G.
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p. 4034 - 4042
(2019/06/24)
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- Flow chemistry synthesis of zolpidem, alpidem and other GABAA agonists and their biological evaluation through the use of in-line frontal affinity chromatography
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The flow of information between chemical and biological research can present a bottleneck in pharmaceutical research. Tools that bridge these disciplines and aid information exchange have therefore clear value. Over the last few years, both synthetic chemistry and biological screening have benefited from automation, and a seamless chemistry-biology interface is now possible. We report here on the use of flow processes to perform synthesis and biological evaluation in an integrated manner. As proof of concept, a flow synthesis of a series of imidazo[1,2-a]pyridines, including zolpidem and alpidem, was developed and connected to a Frontal Affinity Chromatography screening assay to investigate their interaction with Human Serum Albumin (HSA). The Royal Society of Chemistry 2013.
- Guetzoyan, Lucie,Nikbin, Nikzad,Baxendale, Ian R.,Ley, Steven V.
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p. 764 - 769
(2013/03/14)
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- A structure-activity relationship study of the affinity of selected imidazo[1,2-a]pyridine derivatives, congeners of zolpidem, for the ω1-subtype of the benzodiazepine receptor
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A series of 6-substituted 2-aryl-N,N-dimethylimidazol [1,2-a]pyridine-3-acetamides, congeners of zolpidem and alpidem, was synthesized and tested in vitro for binding with the benzodiazepine receptor in the competition with 3H-zolpidem as an ω1-selective radioligand. Molecular electrostatic potential (MEP) and the HOMO and LUMO energies were calculated for the compounds by semi-empirical quantum chemistry methods. The lipophilicity parameter of the compounds, expressed as the logarithm of the octanol-water partition coefficient (log P), was calculated; alternatively, standard values of the Hansch hydrophobic substituent constants π were used. In agreement with earlier investigations on the benzodiazepine receptor ligands with a high preference for the ω1-subtype, a quantitative correlation of the biological data with molecular parameters has revealed a significant dependence (r=0.954) of the binding affinity (IC50) on the deepest MEP minimum, in this case associated with the amide carbonyl oxygen atom. The lipophilicity parameters were found to be of lower significance.
- Lange,Karolak-Wojciechowska,Wejroch,Rump
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