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• W4295648546 abstract "The lack of potent and selective tool compounds with pharmaceutically favorable properties limits the in vivo understanding of muscarinic acetylcholine receptor subtype 5 (M5) biology. Previously, we presented a highly potent and selective M5 antagonist VU6019650 with a suboptimal clearance profile as our second-generation tool compound. Herein, we disclose our ongoing efforts to generate next-generation M5 antagonists with improved clearance profiles. A mix and match approach between VU6019650 (lead) and VU0500325 (HTS hit) generated a piperidine amide-based novel M5 antagonist series. Several analogs within this series, including 29f, provided good on-target potency with improved clearance profiles, though room for improvement remains." @default.
• W4295648546 created "2022-09-14" @default.
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• W4295648546 date "2022-11-01" @default.
• W4295648546 modified "2023-10-02" @default.
• W4295648546 title "Discovery of a potent M5 antagonist with improved clearance profile. Part 1: Piperidine amide-based antagonists" @default.
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• W4295648546 doi "https://doi.org/10.1016/j.bmcl.2022.128988" @default.
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