Roscovitine-Derived, Dual-Specificity Inhibitors of Cyclin-Dependent Kinases and Casein Kinases 1
摘要:
Cyclin-dependent kinases (CDKs) and casein kinases 1 (CK 1) are involved in the two key molecular features of Alzheimer's disease, production of amyloid-beta peptides (extracellular plaques) and hyper-phosphorylation of Tau (intracellular neurofibrillary tangles). A series of 2,6,9-trisubstituted purines, structurally related to the CDK inhibitor roscovitine, have been synthesized. They mainly differ by the substituent on the C-6 position. These compounds were screened for kinase inhibitory activities and antiproliferative effects. Several biaryl derivatives displayed potent inhibition of both CDKs and CK1. In particular, derivative 13a was a potent inhibitor of CDK1/cyclin B (IC50: 220 nM), CDK5/p25 (IC50: 80 nM), and CK1 (IC50: 14 nM). Modeling of these molecules into the ATP-binding pocket of CK1 delta provided a rationale for the increased selectivity toward this kinase. 13a was able to prevent the CK1-dependent production of anyloid-beta in a cell model. CDK/CK1 dual-specificity inhibitors may have important applications in Alzheimer's disease and cancers.
[EN] CARBAMATE COMPOUNDS AND OF MAKING AND USING SAME<br/>[FR] COMPOSÉS CARBAMATES ET LEUR PROCÉDÉ DE FABRICATION ET D'UTILISATION
申请人:ABIDE THERAPEUTICS
公开号:WO2013142307A1
公开(公告)日:2013-09-26
Provided herein are carbamate compounds which may be useful in the treatment of, for example, pain, solid tumors and/or obesity.
本文提供的是可能在治疗疼痛、实体肿瘤和/或肥胖等方面有用的氨基甲酸酯化合物。
[EN] INSULIN SECRETION PROMOTING AGENTS<br/>[FR] ACTIVATEURS DE LA SÉCRÉTION D'INSULINE
申请人:CT HOSPITALIER DE L UNIVERSITE DE MONTREAL
公开号:WO2013016807A1
公开(公告)日:2013-02-07
The present disclosure relates to novel compounds, compositions containing same and methods for treating or preventing a condition associated with a deficient insulin secretion such as diabetes and metabolic syndrome in a subject in need thereof.
[EN] ABHD6 ANTAGONISTS FOR PROMOTING BROWNING OF WHITE ADIPOSE TISSUE AND BROWN ADIPOSE TISSUE FUNCTIONALITY<br/>[FR] ANTAGONISTES ABHD6 FAVORISANT LE BRUNISSEMENT DES TISSUS ADIPEUX BLANCS ET FONCTIONNALITÉ DES TISSUS ADIPEUX BRUNS
申请人:VAL CHUM LTD PARTNERSHIP
公开号:WO2015127559A1
公开(公告)日:2015-09-03
The present disclosure relates to compounds of formula I : compositions containing same and methods for treating or preventing a condition associated with brown adipose tissue dysfunction in a subject and/or for converting white adipose tissue into beige/brite adipose tissue.
A method for producing a biaryl compound, comprising reacting an aromatic organic compound with at least one compound selected from the group consisting of aromatic organoboron compounds and boroxine compounds, in the presence of a zero-valent nickel catalyst, phosphine ligand and base.
PROCESS FOR THE PREPARATION OF TRYPTASE INHIBITORS
申请人:Sanofi-Aventis Deutschland GmbH
公开号:US20130225825A1
公开(公告)日:2013-08-29
This invention is directed to processes for the preparation of a compound of the formula I or salt thereof,
that is useful as a tryptase inhibitor, to intermediates useful in the preparation of such a compound, to processes for the preparation of such intermediates, and to the use of such intermediates for the preparation of such a compound.