- Deuterium-Substituted Pyridin- And Pyrimidin-2-yl-Methylamine Compounds
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Described are deuterium-substituted pyridin- and pyrimidin-2-yl-methylamine compounds of structural Formula (I), which are agonists of 5-hydroxytryptamine receptors. Also described are pharmaceutical compositions comprising the deuterium-substituted pyridin- and pyrimidin-2-yl-methylamine compounds, and methods of use thereof.
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Paragraph 0410; 0411
(2018/04/14)
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- METHOD FOR PREPARING (3-CHLORO-4-FLUOROPHENYL)-(4-FLUORO-4-{[(5METHYL-PYRIMIDIN-2-YLMETHYL)-AMINO]-METHYL}-PIPERIDIN-1-YL)-METHANONE AND NOVEL INTERMEDIATE PYRIMIDINE DERIVATIVES
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The present invention concerns the method for preparing (3-chloro-4-fluorophenyl)-(4-fluoro-4-{[(5-methyl-pyrimidin-2- ylmethyl)-amino]-methyl}-piperidin-1-yl)-methanone of formula (II) by condensation between 5-methyl-pyrimidin-2-methylamine of formula (
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Page/Page column 9
(2008/06/13)
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- High-efficacy 5-HT1A agonists for antidepressant treatment: A renewed opportunity
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We report the discovery of novel 5-HT1A receptor agonists and describe the process that led to the antidepressant candidate 9 (F 15599). 9 has nanomolar affinity for 5-HT1A binding sites and is over 1000-fold selective with respect to the other 5-HT1 receptor subtypes, 5-HT2-7 receptor families, and also numerous GPCRs, transporters, ion channels, and enzymes. In a cellular model of signal transduction, 9 activates h5-HT1A receptors with an efficacy superior to that of the prototypical 5-HT1A agonist (±)-8-OH-DPAT and comparators undergoing clinical trials. After acute oral administration in rats, 9 totally reverses immobility in the forced swimming test and produces behaviors characteristic of 5-HT1A receptor activation. However, these effects occurred at widely separated doses, suggesting that 9 discriminates between distinct populations of 5-HT1A receptors. While the clinical relevance of these observations is still unknown, this opens new perspectives for the treatment of depressive disorders.
- Maurel, Jean Louis,Autin, Jean-Marie,Funes, Philippe,Newman-Tancredi, Adrian,Colpaert, Francis,Vacher, Bernard
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p. 5024 - 5033
(2008/03/13)
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