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• W2801244804 abstract "This letter describes the chemical optimization of a new series of M1 positive allosteric modulators (PAMs) based on a novel benzomorpholine core, developed via iterative parallel synthesis, and culminating in the highly utilized rodent in vivo tool compound, VU0486846 (7), devoid of adverse effect liability. This is the first report of the optimization campaign (SAR and DMPK profiling) that led to the discovery of VU0486846 and details all of the challenges faced in allosteric modulator programs (both steep and flat SAR, as well as subtle structural changes affecting CNS penetration and overall physiochemical and DMPK properties)." @default.
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• W2801244804 date "2018-07-01" @default.
• W2801244804 modified "2023-10-16" @default.
• W2801244804 title "The discovery of VU0486846: steep SAR from a series of M1 PAMs based on a novel benzomorpholine core" @default.
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• W2801244804 doi "https://doi.org/10.1016/j.bmcl.2018.05.009" @default.
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