208110-64-9

Basic information

• Product Name: befiradol
• Synonyms: befiradol;1-(3-Chloro-4-fluorobenzoyl)-4-fluoro-N-[(5-methyl-2-pyridinyl)methyl]-4-piperidinemethanamine;Unii-rat9oha1yh;F 13640;(3-chloro-4-fluorophenyl)-[4-fluoro-4-[[(5-methylpyridin-2-yl)methylamino]methyl]piperidin-1-yl]methanone
• CAS NO: 208110-64-9
• Molecular Formula: C₂₀H₂₂ClF₂N₃O
• Molecular Weight: 393.863
• Mol File: 208110-64-9.mol

Chemical Properties

• Boiling Point: 536.9±50.0 °C(Predicted)
• Appearance: /
• Density: 1.30
• PKA: 8.01±0.20(Predicted)
• CAS DataBase Reference: befiradol(CAS DataBase Reference)
• NIST Chemistry Reference: befiradol(208110-64-9)
• EPA Substance Registry System: befiradol(208110-64-9)

Safety Data

• Hazardous Substances Data: 208110-64-9(Hazardous Substances Data)

Upstream product

• 448920-98-7 2-[1-[(3-chloro-4-fluorophenyl)carbonyl]-4-fluoropiperidin-4-yl]-2-hydroxyacetonitrile 
• 45715-08-0 ((5-methyl-pyridin-2-yl)-methyl)-amine 
• 280-57-9 1,4-diaza-bicyclo[2.2.2]octane 
• 161647-06-9 (5-methylpyridin-2-yl)methylamine (dihydrochloride) 
• 403-16-7 3-chloro-4-fluorobenzoic acid 
• 161647-06-9 [5-methylpyridin-2-yl]methanamine hydrochloride 
• 208111-38-0 N-(3-chloro-4-fluorobenzoyl)-4-fluoro-4-phthalimidomethylpiperidine 
• 208111-37-9 N-(3-chloro-4-fluorobenzoyl)-4-fluoro-4-(4-methylphenylsulonuloxymethyl)-piperidine 
• 208111-39-1 N-(3-chloro-4-fluorobenzoyl)-4-fluoro-4-aminomethylpiperidine 
• 208111-36-8 N-(3-chloro-4-fluorobenzoyl)-4-fluoro-4-hydroxymethylpiperidine 
• 208111-51-7 N-(3-chloro-4-fluorobenzoyl)-1-oxa-6-azaspiro<2,5>octane 
• 223632-64-2 1-[(3-chloro-4-fluorophenyl)carbonyl]piperidin-4-one 
• 65055-17-6 3-chloro-4-fluorobenzoyl chloride 
• 177-11-7 4,4-ethylenedioxy-piperidine 

Downstream Products

• 1256167-79-9 N-[1-(3-chloro-4-fluorobenzoyl)-4-fluoropiperidin-4-yl]methyl-N-methyl-N-(5-methylpyridin-2-yl)methylamine 

Relevant articles and documents

Conformational analysis and crystal structure of {[1-(3-chloro-4- fluorobenzoyl)-4-fluoropiperidin-4yl]methyl}[(5-methylpyridin-2-yl)methyl]amine, fumaric acid salt

{[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).

Deuterium-Substituted Pyridin- And Pyrimidin-2-yl-Methylamine Compounds

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.

Novel pyridylmethylamines as highly selective 5-HT1A superagonists

To further improve the maximal serotonergic efficacy and better understand the configurational requirements for 5-HT1A binding and activation, we generated and biologically investigated structural variants of the lead structure befiradol. For a bioisosteric replacement of the 3-chloro-4-fluoro moiety, a focused library of 63 compounds by solution phase parallel synthesis was developed. Target binding of our compound collection was investigated, and their affinities for 5-HT2, α1, and α2-adrenergic as well as D1-D4 dopamine receptors were compared. For particularly interesting test compounds, intrinsic activities at 5-HT1A were examined in vitro employing a GTPγS assay. The investigation guided us to highly selective 5HT1A superagonists. The benzothiophene-3-carboxamide 8bt revealed almost exclusive 5HT1A recognition with a Ki value of 2.7 nM and a maximal efficacy of 124%. To get insights into the bioactive conformation of our compound collection, we synthesized conformationally constrained bicyclic scaffolds when SAR data indicated a chair-type geometry and an equatorially dispositioned aminomethyl substituent for the 4,4-disubstituted piperidine moiety.

Synthesis method and intermediates of pyridin-2-yl-methylamine

The invention concerns a novel method for preparing pyridin-2-yl-methylamine derivatives by reducing amination of cyanohydrins.

Pyridylmethylamines polypyridine-2-yl-synthesis of the intermediate body,

The invention concerns a novel method for preparing pyridin-2-yl-methylamine derivatives by reducing amination of cyanohydrins.

Novel derivatives of 2-pyridinemethylamine as selective, potent, and orally active agonists at 5-HT(1A) receptors

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.