Discovery of novel pyridazine derivatives as glucose transporter type 4 (GLUT4) translocation activators.
Basic Information
ID: ALA4340562
Journal: Bioorg Med Chem Lett
Title: Discovery of novel pyridazine derivatives as glucose transporter type 4 (GLUT4) translocation activators.
Authors: Tsuji T, Yamaguchi M, Kuroyanagi J, Furuzono S, Konishi M, Terayama K, Tanaka J, Saito M, Kobayashi Y.
Abstract: We report herein the synthesis and structure-activity relationships (SAR) of a series of pyridazine derivatives with the activation of glucose transporter type 4 (GLUT4) translocation. Through a cell-based phenotype screening in L6-GLUT4-myc myoblasts and functional glucose uptake assays, lead compound 1a was identified as a functional small molecule. After further derivatization, the thienopyridazine scaffold as the central ring (B-part) was revealed to have potent GLUT4 translocation activities. Consequently, we obtained promising compound 26b, which showed a significant blood glucose lowering effect in the severe diabetic mice model (10-week aged db/db mice) after oral dosing even at 10 mg/kg, implying that our pyridazine derivatives have potential to become novel therapeutic agents for diabetes mellitus.
CiteXplore: 31101471
DOI: 10.1016/j.bmcl.2019.05.013
Patent ID: ┄