Safety of 2-Chloro-5-pyridinesulfonyl chloride. Aromatic compounds can be divided into two categories: single heterocycles and fused heterocycles. Compound: 2-Chloro-5-pyridinesulfonyl chloride, is researched, Molecular C5H3Cl2NO2S, CAS is 6684-39-5, about Small Molecule Disruptors of the Glucokinase-Glucokinase Regulatory Protein Interaction: 3. Structure-Activity Relationships within the Aryl Carbinol Region of the N-Arylsulfonamido-N’-arylpiperazine Series. Author is Nishimura, Nobuko; Norman, Mark H.; Liu, Longbin; Yang, Kevin C.; Ashton, Kate S.; Bartberger, Michael D.; Chmait, Samer; Chen, Jie; Cupples, Rod; Fotsch, Christopher; Helmering, Joan; Jordan, Steven R.; Kunz, Roxanne K.; Pennington, Lewis D.; Poon, Steve F.; Siegmund, Aaron; Sivits, Glenn; Lloyd, David J.; Hale, Clarence; St. Jean, David J..
We have recently reported a novel approach to increase cytosolic glucokinase (GK) levels through the binding of a small mol. to its endogenous inhibitor, glucokinase regulatory protein (GKRP). These initial investigations culminated in the identification of 2-(4-((2S)-4-((6-amino-3-pyridinyl)sulfonyl)-2-(1-propyn-1-yl)-1-piperazinyl)phenyl)-1,1,1,3,3,3-hexafluoro-2-propanol (I, AMG-3969), a compound that effectively enhanced GK translocation and reduced blood glucose levels in diabetic animals. Herein we report the results of our expanded SAR investigations that focused on modifications to the aryl carbinol group of this series. Guided by the X-ray cocrystal structure of compound I bound to hGKRP, we identified several potent GK-GKRP disruptors bearing a diverse set of functionalities in the aryl carbinol region. Among them, sulfoximine and pyridinyl derivatives II and III possessed excellent potency as well as favorable PK properties. When dosed orally in db/db mice, both compounds significantly lowered fed blood glucose levels (up to 58%).
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Chiral nitrogen ligands in late transition metal-catalysed asymmetric synthesis—I. Addressing the problem of ligand lability in rhodium-catalysed hydrosilations,
Nitrogen-Containing Ligands for Asymmetric Homogeneous and Heterogeneous Catalysis