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Discovery of 2-(3,4-dichlorophenoxy)-N-(2-morpholin-4-ylethyl)acetamide: A selective σ1 receptor ligand with antinociceptive effect.
Journal article

Discovery of 2-(3,4-dichlorophenoxy)-N-(2-morpholin-4-ylethyl)acetamide: A selective σ1 receptor ligand with antinociceptive effect.

  • Navarrete-Vázquez G Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos 62209, Mexico, Mexico. Electronic address: gabriel_navarrete@uaem.mx.
  • Austrich-Olivares A Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos 62209, Mexico, Mexico.
  • Godínez-Chaparro B Departamento de Sistemas Biológicos, División de Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana-Xochimilco, México D.F., 04960, Mexico, Mexico.
  • Hidalgo-Figueroa S Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos 62209, Mexico, Mexico.
  • Estrada-Soto S Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos 62209, Mexico, Mexico.
  • Hernández-Núñez E Cátedra CONACyT, Departamento de Recursos del Mar, Centro de Investigación y de Estudios Avanzados del IPN, Unidad Mérida, 97310 Yucatán, Mexico, Mexico.
  • Torres-Gómez H Institute for Chemistry and Chemical Biology, Zürich University of Applied Sciences, 8820 Wädenswil, Switzerland, Switzerland; Institut für Pharmazeutische und Medizinische Chemie der Westfälischen Wilhelms-Universität Münster, D-48149 Münster, Germany, Germany.
  • Schepmann D Institut für Pharmazeutische und Medizinische Chemie der Westfälischen Wilhelms-Universität Münster, D-48149 Münster, Germany, Germany.
  • Wünsch B Institut für Pharmazeutische und Medizinische Chemie der Westfälischen Wilhelms-Universität Münster, D-48149 Münster, Germany, Germany.
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  • 2016-04-06
Published in:
  • Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. - 2016
Binding assay
Formalin test
Pain
σ receptors
Acetamides
Analgesics
Animals
Catalytic Domain
Female
Injections, Spinal
Ligands
Molecular Docking Simulation
Morpholines
Rats
Rats, Wistar
Receptors, sigma
Reference Standards
English Compound 2-(3,4-dichlorophenoxy)-N-(2-morpholin-4-ylethyl)acetamide (1) was designed, prepared and the in vitro binding evaluation against σ1 and σ2 receptors was measured. Compound 1 showed high σ1 receptor affinity (Ki=42 nM) and it was 36-times more selective for σ1 than σ2 receptor. Also, it was performed a molecular docking of compound 1 into the ligand binding pocket homology model of σ1 receptor, showing a salt bridge between the ionized morpholine ring and Asp126, as well as important short contacts with residues Tyr120, His154 and Trp164. Ligand efficiency indexes and predicted toxicity analysis revealed an excellent intrinsic quality of 1. The antinociceptive effect of compound 1 was determined using the formalin test. The ipsilateral local peripheral (10-300 μg/paw) and intrathecal (100 μg/rat) administration of 1 produced a reduction in formalin-induced nociception. The in vivo results indicated that 1 may be effective in treating inflammatory pain.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://sonar.ch/global/documents/61607
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