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• W2345434979 abstract "The 5-HT7 serotonin receptor is revealing a promising target for innovative therapeutic strategies of neurodevelopmental and neuropsychiatric disorders. Here, we report the synthesis of thirty long-chain arylpiperazine analogs of the selective and brain penetrant 5-HT7 receptor agonist LP-211 (1) designed to enhance stability towards microsomal oxidative metabolism. Commonly used medicinal chemistry strategies were used (i.e., reduction of overall lipophilicity, introduction of electron-withdrawing groups, blocking of potential vulnerable sites of metabolism), and in vitro microsomal stability was tested. The data showed that the adopted design strategy does not directly translate into improvements in stability. Instead, the metabolic stability of the compounds was related to the presence of specific substituents in well-defined regions of the molecule. The collected data allowed for the construction of a machine learning model that, in a given chemical space, is able to describe and quantitatively predict the metabolic stability of the compounds. The majority of the synthesized compounds maintained high affinity for 5-HT7 receptors and showed selectivity towards 5-HT6 and dopamine D2 receptors and different selectivity for 5-HT1A and α1 adrenergic receptors. Compound 50 showed 3-fold higher in vitro stability towards oxidative metabolism than 1 and was able to stimulate neurite outgrowth in neuronal primary cultures through the 5-HT7 receptor in a shorter time and at a lower concentration than the agonist 1. A preliminary disposition study in mice revealed that compound 50 was metabolically stable and was able to pass the blood–brain barrier, thus representing a new tool for studying the pharmacotherapeutic potential of 5-HT7 receptor in vivo." @default.
• W2345434979 created "2016-06-24" @default.
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• W2345434979 date "2016-09-01" @default.
• W2345434979 modified "2023-09-24" @default.
• W2345434979 title "Structural modifications of the serotonin 5-HT7 receptor agonist N-(4-cyanophenylmethyl)-4-(2-biphenyl)-1-piperazinehexanamide (LP-211) to improve in vitro microsomal stability: A case study" @default.
• W2345434979 cites W1673495827 @default.
• W2345434979 cites W1951576969 @default.
• W2345434979 cites W1966684221 @default.
• W2345434979 cites W1968506227 @default.
• W2345434979 cites W1974254541 @default.
• W2345434979 cites W1975875968 @default.
• W2345434979 cites W1977298694 @default.
• W2345434979 cites W1978570887 @default.
• W2345434979 cites W1980337077 @default.
• W2345434979 cites W1980603198 @default.
• W2345434979 cites W1988195734 @default.
• W2345434979 cites W1989448566 @default.
• W2345434979 cites W1991191854 @default.
• W2345434979 cites W2001736610 @default.
• W2345434979 cites W2002000389 @default.
• W2345434979 cites W2006905513 @default.
• W2345434979 cites W2007472184 @default.
• W2345434979 cites W2009867031 @default.
• W2345434979 cites W2014125047 @default.
• W2345434979 cites W2017708470 @default.
• W2345434979 cites W2018417599 @default.
• W2345434979 cites W2030577605 @default.
• W2345434979 cites W2031069836 @default.
• W2345434979 cites W2034542541 @default.
• W2345434979 cites W2040887230 @default.
• W2345434979 cites W2040903359 @default.
• W2345434979 cites W2043820906 @default.
• W2345434979 cites W2045517587 @default.
• W2345434979 cites W2049812048 @default.
• W2345434979 cites W2051379110 @default.
• W2345434979 cites W2053105004 @default.
• W2345434979 cites W2057175067 @default.
• W2345434979 cites W2064669765 @default.
• W2345434979 cites W2066701183 @default.
• W2345434979 cites W2067345113 @default.
• W2345434979 cites W2068266573 @default.
• W2345434979 cites W2080461836 @default.
• W2345434979 cites W2080876500 @default.
• W2345434979 cites W2082152632 @default.
• W2345434979 cites W2082441632 @default.
• W2345434979 cites W2086063461 @default.
• W2345434979 cites W2090505208 @default.
• W2345434979 cites W2091205528 @default.
• W2345434979 cites W2098349518 @default.
• W2345434979 cites W2102438497 @default.
• W2345434979 cites W2107757712 @default.
• W2345434979 cites W2110248023 @default.
• W2345434979 cites W2114004211 @default.
• W2345434979 cites W2119008659 @default.
• W2345434979 cites W2121776789 @default.
• W2345434979 cites W2122284941 @default.
• W2345434979 cites W2125560201 @default.
• W2345434979 cites W2133990480 @default.
• W2345434979 cites W2136556186 @default.
• W2345434979 cites W2153506277 @default.
• W2345434979 cites W2157914995 @default.
• W2345434979 cites W2159326671 @default.
• W2345434979 cites W2159887157 @default.
• W2345434979 cites W2159923168 @default.
• W2345434979 cites W2163491585 @default.
• W2345434979 cites W2167637850 @default.
• W2345434979 cites W2189824080 @default.
• W2345434979 cites W2317188577 @default.
• W2345434979 cites W2321928955 @default.
• W2345434979 cites W2326124692 @default.
• W2345434979 cites W2326234435 @default.
• W2345434979 cites W2326965110 @default.
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• W2345434979 doi "https://doi.org/10.1016/j.ejmech.2016.05.005" @default.
• W2345434979 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/27318552" @default.
• W2345434979 hasPublicationYear "2016" @default.
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