- Thienylhalomethylketones: Irreversible glycogen synthase kinase 3 inhibitors as useful pharmacological tools
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Thienylhalomethylketones, whose chemical, biological, and pharmaceutical data are here reported, are the first irreversible inhibitors of GSK-3β described to date. Their inhibitory activity is likely related to the cysteine residue present in the ATP-binding site, which is proposed as a relevant residue for modulation of GSK-3 activity. The good cell permeability of the compounds allows them to be used in different cell models. Overall, the results presented here support the potential use of halomethylketones as pharmacological tools for the study of GSK-3β functions and suggest a new mechanism for GSK-3β inhibition that may be considered for further drug design.
- Perez, Daniel I.,Conde, Santiago,Perez, Concepcion,Gil, Carmen,Simon, Diana,Wandosell, Francisco,Moreno, Francisco J.,Gelpi, Jose L.,Luque, Francisco J.,Martinez, Ana
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scheme or table
p. 6914 - 6925
(2010/02/28)
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- Thienyl and Phenyl α-Halomethyl Ketones: New Inhibitors of Glycogen Synthase Kinase (GSK-3β) from a Library of Compound Searching
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Glycogen synthase kinase (GSK-3β) plays a crucial role in Alzheimer's disease (AD). Its inhibition is a valid approach to the treatment of AD. In this initial letter, some thienyl and phenyl α-halomethyl ketones are described as new non-ATP competitive inhibitors of GSK-3β. They are considered as lead compounds for designing and synthesizing new series, to carry out SAR studies, clear up the mechanism of action, and, in general, evaluate their therapheutical usefulness.
- Conde, Santiago,Pérez, Daniel I.,Martínez, Ana,Perez, Concepción,Moreno, Francisco J.
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p. 4631 - 4633
(2007/10/03)
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- Bromothiophene Reactions. I. Friedel-Crafts Acylation
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Friedel-Crafts acylation of 2,5-dibromo- and 2,3,5-tribromothiophenes with different acyl chlorides and anhydrous aluminium trichloride has been studied.The reaction afforded a mixture of acyl derivatives and tetrabromothiophene.The results obtained suggest a mechanism which involves the formation of bromine cations in the reaction medium.Several products obtained in this reaction are described.
- Agua, M. J. del,Alvarez-Insua, A. S.,Conde, S.
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p. 1345 - 1347
(2007/10/02)
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