Synthesis and SAR of a novel Kir6.2/SUR1 channel opener scaffold identified by HTS.

Cayden J Dodd, Keagan S Chronister, Upendra Rathnayake, Lauren C Parr, Kangjun Li,Sichen Chang,Dehui Mi,Emily L Days,Joshua A Bauer,Hyekyung P Cho,Olivier Boutaud,Jerod S Denton,Craig W Lindsley,Changho Han

Bioorganic & medicinal chemistry letters（2023）

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摘要

Kir6.2/SUR1 is an ATP-regulated potassium channel that acts as an intracellular metabolic sensor, controlling insulin and appetite-stimulatory neuropeptides secretion. In this Letter, we present the SAR around a novel Kir6.2/SUR1 channel opener scaffold derived from an HTS screening campaign. New series of compounds with tractable SAR trends and favorable potencies are reported.

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