223632-64-2Relevant academic research and scientific papers
Novel Aryloxyethyl Derivatives of 1-(1-Benzoylpiperidin-4-yl)methanamine as the Extracellular Regulated Kinases 1/2 (ERK1/2) Phosphorylation-Preferring Serotonin 5-HT1A Receptor-Biased Agonists with Robust Antidepressant-like Activity
Sniecikowska, Joanna,Gluch-Lutwin, Monika,Bucki, Adam,Wieckowska, Anna,Siwek, Agata,Jastrzebska-Wiesek, Magdalena,Partyka, Anna,Wilczyńska, Daria,Pytka, Karolina,Pociecha, Krzysztof,Cios, Agnieszka,Wyska, Elzbieta,Wesolowska, Anna,Pawlowski, Maciej,Varney, Mark A.,Newman-Tancredi, Adrian,Kolaczkowski, Marcin
, p. 2750 - 2771 (2019)
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+ mobiliz
Deuterium-Substituted Pyridin- And Pyrimidin-2-yl-Methylamine Compounds
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, (2018/04/14)
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.
Conformational analysis and crystal structure of {[1-(3-chloro-4- fluorobenzoyl)-4-fluoropiperidin-4yl]methyl}[(5-methylpyridin-2-yl)methyl]amine, fumaric acid salt
Ribet,Pena,Maurel,Belin,Tillard,Vacher,Bonnaud,Colpaert
, p. 353 - 363 (2007/10/03)
{[1-(3-Chloro-4-fluorobenzoyl)-4-fluoropiperidin-4yl]methyl} [(5-methylpyridin-2-yl)methyl]amine, fumaric acid salt (C20H 22ClF2N3O, C4H4O 4) (1) was synthesized and characterized by the complete 1H, 13C and 19F NMR analyses. The conformation of the piperidin ring, in the solution state, was particularly studied from the coupling constants determined by recording a double-quantum filtered COSY experiment in phase-sensitive mode. 1H NMR line-shape analysis was used, at temperatures varying between -5 and +60 °C, to determine the enthalpy of activation of the rotational barrier around the CN bond. Compound 1 crystallizes in the triclinic space group P1 with a = 8.517(3) A, b = 12.384(2) A, c = 12.472(3) A, α = 70.88(2)°, β = 82.04(2)°, γ = 83.58(2)°. The results strongly indicate that the solid and solution conformations are similar. Thermal stability and phases transitions were investigated by thermal gravimetric analysis (TGA) and differential scanning calorimetry (DSC). Furthermore polymorphism screening was studied from recrystallization of 1 performed in seven solvents and by slurry conversion in water. The X-ray powder diffraction (XRPD) and differential scanning calorimetry results suggested that 1 crystallizes into one crystalline form which melts at 157 °C (ΔH = 132 J g-1).
Novel derivatives of 2-pyridinemethylamine as selective, potent, and orally active agonists at 5-HT(1A) receptors
Vacher, Bernard,Bonnaud, Bernard,Funes, Philippe,Jubault, Nathalie,Koek, Wouter,Assié, Marie-Bernadette,Cosi, Cristina,Kleven, Mark
, p. 1648 - 1660 (2007/10/03)
The aim of this work was to improve the oral bioavailability of a recently discovered, novel structural class of 5-HT(1A) receptor agonists: aryl-{[4-(6-R-pyridin-2-ylmethyl)-amino]-methyl}piperidin-1-yl-methanone. Incorporation of a fluorine atom in the β-position to the amino function in the side chain led to analogues that exhibited, in general, enhanced and long-lasting 5-HT(1A) agonist activity in rats after oral administration. Location of the fluorine atom at the C-4 position of the piperidine ring was the most favorable, and among the various substituents tested, the ability of the fluorine was unique in improving the oral activity of this family of ligands. Thus, the derivatives 39, 46, and 61 bound with higher affinity and selectivity to 5-HT(1A) receptors (versus dopaminergic D2 and adrenergic α1 receptors) and displayed more potent 5-HT(1A) agonist activity in vitro and in vivo than their C-4 desfluoro analogues. To examine the relationship between the conformation of the pharmacophore and the level of agonistic activity of this type of ligand, we synthesized a series of 3-chloro-4- fluorophenyl-(4-fluoro-4{[(5-(H or CH3)-6-R-pyridin-2-ylmethyl)-amino]- methyl}-piperidin-1-yl-methanone derivatives and found that the combination of a 5-methyl and a 6-methylamino substituent on the pyridine ring synergistically affected their 5-HT(1A) agonist properties. Thus, the 3- chloro-4-fluorophenyl-(4-fluoro-4{[(5-methyl-6-methylamino-pyridin-2- ylmethyl)-amino]-methyl}-piperidin-1-yl-methanone 40 behaved as a more potent 5-HT(1A) receptor agonist in vitro and in vivo than its 5- unsubstituted analogue 38. The antidepressant potential of the lead compounds 40, 45, and 54 was examined by means of the forced swimming test (FST) in rats. The results indicated that, after a single oral administration, these compounds inhibited immobility in the FST more potently and more extensively than the clinically used antidepressant imipramine. Thus, 40, 45, and 54 are potent, orally active 5-HT(1A) receptor agonists with marked antidepressant potential.
