- Biological evaluation of pyridone alkaloids on the endocannabinoid system
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Naturally occurring pyridone alkaloids as well as synthetic derivatives were previously shown to induce neurite outgrowth. However, the molecular basis for this biological effect remains poorly understood. In this work, we have prepared new pyridones, and tested the effect of thirteen 4-hydroxy-2-pyridone derivatives on the components of the endocannabinoid system. Investigation of binding affinities towards CB1 and CB2 receptors led to the identification of a compound binding selectively to CB1 (12). Compound 12 and a closely related derivative (11) also inhibited anandamide (AEA) hydrolysis by fatty acid amide hydrolase. Interestingly, none of the compounds tested showed any effect on 2-AG hydrolysis by monoacylglycerol lipase at 10 μM. Assessment of AEA uptake did, however, lead to the identification of four inhibitors with IC50 values in the submicromolar range and high selectivity over the other components of the endocannabinoid system.
- Chicca, Andrea,Berg, Regina,Jessen, Henning J.,Marck, Nicolas,Schmid, Fabian,Burch, Patrick,Gertsch, Jürg,Gademann, Karl
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- Combined Proteomic and In Silico Target Identification Reveal a Role for 5-Lipoxygenase in Developmental Signaling Pathways
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Identification and validation of the targets of bioactive small molecules identified in cell-based screening is challenging and often meets with failure, calling for the development of new methodology. We demonstrate that a combination of chemical proteom
- Brand, Silke,Roy, Sayantani,Schr?der, Peter,Rathmer, Bernd,Roos, Jessica,Kapoor, Shobhna,Patil, Sumersing,Pommerenke, Claudia,Maier, Thorsten,Janning, Petra,Eberth, Sonja,Steinhilber, Dieter,Schade, Dennis,Schneider, Gisbert,Kumar, Kamal,Ziegler, Slava,Waldmann, Herbert
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p. 1095 - 23,1106
(2018/06/11)
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- PYRIDONE GPR119 G PROTEIN-COUPLED RECEPTOR AGONISTS
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Novel compounds are provided which are GPR119 G protein-coupled receptor modulators. GPR119 G protein-coupled receptor modulators are useful in treating, preventing, or slowing the progression of diseases requiring GPR 119 G protein-coupled receptor modulator therapy. These novel compounds have the structure Formula I or Formula IA.
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Page/Page column 116
(2009/02/11)
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- Total synthesis of pyridovericin
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The total synthesis of the naturally occurring kinase inhibitor pyridovericin 1 is reported. A flexible and efficient synthesis has been accomplished in good yield from readily available 2,4-dihydroxypyridine. Pyridovericin is a key intermediate in our pr
- Irlapati, Nageswara Rao,Adlington, Robert M.,Conte, Aurelia,Pritchard, Gareth J.,Marquez, Rodolfo,Baldwin, Jack E.
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p. 9307 - 9317
(2007/10/03)
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- Total synthesis of pyridovericin: studies toward the biomimetic synthesis of pyridomacrolidin.
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[reaction: see text] The total synthesis of the novel metabolite pyridovericin 1 is reported. The synthesis of this key intermediate in our proposed biomimetic synthesis of pyridomacrolidin 2 has been accomplished in good yield from readily available 2,4-dihydroxypyridine.
- Baldwin, Jack E,Adlington, Robert M,Conte, Aurelia,Irlapati, Nageswara Rao,Marquez, Rodolfo,Pritchard, Gareth J
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p. 2125 - 2127
(2007/10/03)
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