7544-57-2Relevant articles and documents
Discovery of Highly Selective Inhibitors of Calmodulin-Dependent Kinases That Restore Insulin Sensitivity in the Diet-Induced Obesity in Vivo Mouse Model
Fromont, Christophe,Atzori, Alessio,Kaur, Divneet,Hashmi, Lubna,Greco, Graziella,Cabanillas, Alejandro,Nguyen, Huy Van,Jones, D. Heulyn,Garzón, Miguel,Varela, Ana,Stevenson, Brett,Iacobini, Greg P.,Lenoir, Marc,Rajesh, Sundaresan,Box, Clare,Kumar, Jitendra,Grant, Paige,Novitskaya, Vera,Morgan, Juliet,Sorrell, Fiona J.,Redondo, Clara,Kramer, Andreas,Harris, C. John,Leighton, Brendan,Vickers, Steven P.,Cheetham, Sharon C.,Kenyon, Colin,Grabowska, Anna M.,Overduin, Michael,Berditchevski, Fedor,Weston, Chris J.,Knapp, Stefan,Fischer, Peter M.,Butterworth, Sam
, p. 6784 - 6801 (2020)
Polymorphisms in the region of the calmodulin-dependent kinase isoform D (CaMK1D) gene are associated with increased incidence of diabetes, with the most common polymorphism resulting in increased recognition by transcription factors and increased protein expression. While reducing CaMK1D expression has a potentially beneficial effect on glucose processing in human hepatocytes, there are no known selective inhibitors of CaMK1 kinases that can be used to validate or translate these findings. Here we describe the development of a series of potent, selective, and drug-like CaMK1 inhibitors that are able to provide significant free target cover in mouse models and are therefore useful as in vivo tool compounds. Our results show that a lead compound from this series improves insulin sensitivity and glucose control in the diet-induced obesity mouse model after both acute and chronic administration, providing the first in vivo validation of CaMK1D as a target for diabetes therapeutics.
SULPHONYL UREA DERIVATIVES AS NLRP3 INFLAMMASOME MODULATORS
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, (2019/07/13)
The present disclosure relates to compounds of Formula (I): (I) and to their pharmaceutically acceptable salts, pharmaceutical compositions, methods of use, and methods for their preparation. The compounds disclosed herein are useful for inhibiting the maturation of cytokines of the IL-1 family by inhibiting inflammasomes and may be used in the treatment of disorders in which inflammasome activity is implicated, such as inflammatory, autoinflammatory and autoimmune diseases and cancers.
Organocatalysis with a fluorous tag: Asymmetric reduction of imines with trichlorosilane catalyzed by amino acid-derived formamides
Malkov, Andrei V.,Figlus, Marek,Stoncius, Sigitas,Kocovsky, Pavel
, p. 1315 - 1325 (2007/10/03)
(Chemical Equation Presented) Asymmetric reduction of ketimines 1 with trichlorosilane can be catalyzed by N-methylvaline-derived Lewis-basic formamides 3a-d with high enantioselectivity (≤95% ee) and low catalyst loading (1-5 mol %) at room temperature i
