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• W2912000934 abstract "Novel 1-(1-benzoylpiperidin-4-yl)methanamine derivatives were designed as biased agonists of serotonin 5-HT1A receptors. The compounds were tested in signal transduction assays (ERK1/2 phosphorylation, cAMP inhibition, Ca2+ mobilization, and β-arrestin recruitment) which identified ERK1/2 phosphorylation-preferring aryloxyethyl derivatives. The novel series showed high 5-HT1A receptor affinity, >1000-fold selectivity versus noradrenergic α1, dopamine D2, serotonin 5-HT2A, histamine H1, and muscarinic M1 receptors, and favorable druglike properties (CNS-MPO, Fsp3, LELP). The lead structure, (3-chloro-4-fluorophenyl)(4-fluoro-4-(((2-(pyridin-2-yloxy)ethyl)amino)methyl)piperidin-1-yl)methanone (17, NLX-204), displayed high selectivity in the SafetyScreen44 panel (including hERG channel), high solubility, metabolic stability, and Caco-2 penetration and did not block CYP3A4, CYP2D6 isoenzymes, or P-glycoprotein. Preliminary in vivo studies confirmed its promising pharmacokinetic profile. 17 also robustly stimulated ERK1/2 phosphorylation in rat cortex and showed highly potent (MED = 0.16 mg/kg) and efficacious antidepressant-like activity, totally eliminating immobility in the rat Porsolt test. These data suggest that the present 5-HT1A receptor-biased agonists could constitute promising antidepressant drug candidates." @default.
• W2912000934 created "2019-02-21" @default.
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• W2912000934 date "2019-02-05" @default.
• W2912000934 modified "2023-10-17" @default.
• W2912000934 title "Novel Aryloxyethyl Derivatives of 1-(1-Benzoylpiperidin-4-yl)methanamine as the Extracellular Regulated Kinases 1/2 (ERK1/2) Phosphorylation-Preferring Serotonin 5-HT_1A Receptor-Biased Agonists with Robust Antidepressant-like Activity" @default.
• W2912000934 cites W1182581869 @default.
• W2912000934 cites W1524934458 @default.
• W2912000934 cites W1588173517 @default.
• W2912000934 cites W1663154925 @default.
• W2912000934 cites W1710423957 @default.
• W2912000934 cites W1904678284 @default.
• W2912000934 cites W1920429098 @default.
• W2912000934 cites W1943873295 @default.
• W2912000934 cites W1963822402 @default.
• W2912000934 cites W1963940427 @default.
• W2912000934 cites W1966173192 @default.
• W2912000934 cites W1971297095 @default.
• W2912000934 cites W1973386992 @default.
• W2912000934 cites W1975182501 @default.
• W2912000934 cites W1975691556 @default.
• W2912000934 cites W1984815383 @default.
• W2912000934 cites W1992584151 @default.
• W2912000934 cites W2002338226 @default.
• W2912000934 cites W2003979487 @default.
• W2912000934 cites W2006460397 @default.
• W2912000934 cites W2014192652 @default.
• W2912000934 cites W2016575780 @default.
• W2912000934 cites W2017727557 @default.
• W2912000934 cites W2018453465 @default.
• W2912000934 cites W2026478054 @default.
• W2912000934 cites W2026490774 @default.
• W2912000934 cites W2027566489 @default.
• W2912000934 cites W2030215451 @default.
• W2912000934 cites W2030260775 @default.
• W2912000934 cites W2036801804 @default.
• W2912000934 cites W2045157956 @default.
• W2912000934 cites W2046822118 @default.
• W2912000934 cites W2047265855 @default.
• W2912000934 cites W2050792705 @default.
• W2912000934 cites W2053114570 @default.
• W2912000934 cites W2057804290 @default.
• W2912000934 cites W2058725970 @default.
• W2912000934 cites W2060809301 @default.
• W2912000934 cites W2065060087 @default.
• W2912000934 cites W2067412138 @default.
• W2912000934 cites W2068405118 @default.
• W2912000934 cites W2069096415 @default.
• W2912000934 cites W2072880669 @default.
• W2912000934 cites W2074760640 @default.
• W2912000934 cites W2083549526 @default.
• W2912000934 cites W2085381168 @default.
• W2912000934 cites W2091064555 @default.
• W2912000934 cites W2091529029 @default.
• W2912000934 cites W2092933199 @default.
• W2912000934 cites W2103218986 @default.
• W2912000934 cites W2105571318 @default.
• W2912000934 cites W2113364934 @default.
• W2912000934 cites W2114650590 @default.
• W2912000934 cites W2115227371 @default.
• W2912000934 cites W2116151143 @default.
• W2912000934 cites W2119199305 @default.
• W2912000934 cites W2124037868 @default.
• W2912000934 cites W2130081888 @default.
• W2912000934 cites W2135732933 @default.
• W2912000934 cites W2140206721 @default.
• W2912000934 cites W2146978055 @default.
• W2912000934 cites W2161618882 @default.
• W2912000934 cites W2163419022 @default.
• W2912000934 cites W2163879184 @default.
• W2912000934 cites W2172260891 @default.
• W2912000934 cites W2239364995 @default.
• W2912000934 cites W2275718008 @default.
• W2912000934 cites W2277316067 @default.
• W2912000934 cites W2330961915 @default.
• W2912000934 cites W2332896222 @default.
• W2912000934 cites W2396454338 @default.
• W2912000934 cites W2441571183 @default.
• W2912000934 cites W2512483042 @default.
• W2912000934 cites W2518741199 @default.
• W2912000934 cites W2549512121 @default.
• W2912000934 cites W2588408561 @default.

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