Yuusuke Tamura, Ippei Morita, Yu Hinata, Eiichi Kojima, Hiroki Ozasa, Hidaka Ikemoto, Mutsumi Asano, Toshihiro Wada, Yoko Hayasaki-Kajiwara, Takanori Iwasaki, Kenichi Matsumura
Bioorganic & medicinal chemistry letters 2022 Jul 15AMP-activated protein kinase (AMPK) has been shown to play an important role in the beneficial effects of exercise on glucose and lipid metabolism in skeletal muscle and liver. Therefore, activation of AMPK has been proposed as an attractive strategy for the treatment of metabolic disorders, such as type 2 diabetes. Many of existing AMPK activators bearing diverse chemical structure were reported. However, there have been few reports of direct AMPK activator with high potency for β2-AMPK isoform, which is thought to be important for glucose homeostasis, and their chemical structure is limited to benzimidazole core. We describe herein our efforts for identification of novel AMPK activator. Our newly designed 4-azaindole derivative 16g exhibited single-digit nM in vitro activity, and chronic treatment with 16g led to dose-dependent improvement in HbA1c as well as decrease in hepatic lipid accumulation in diabetic animal model. Copyright © 2022 Elsevier Ltd. All rights reserved.
Yuusuke Tamura, Ippei Morita, Yu Hinata, Eiichi Kojima, Hiroki Ozasa, Hidaka Ikemoto, Mutsumi Asano, Toshihiro Wada, Yoko Hayasaki-Kajiwara, Takanori Iwasaki, Kenichi Matsumura. Identification of novel indole derivatives as highly potent AMPK activators with anti-diabetic profiles. Bioorganic & medicinal chemistry letters. 2022 Jul 15;68:128769
PMID: 35513222
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