Pyridin-2(1H)one derivatives: A possible new class of therapeutics for mechanical allodynia - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue European Journal of Medicinal Chemistry Année : 2019

Pyridin-2(1H)one derivatives: A possible new class of therapeutics for mechanical allodynia

Alexia Visseq
  • Fonction : Auteur
Amélie Descheemaeker
  • Fonction : Auteur
Nicolas Pinto-Pardo
Lionel Nauton
  • Fonction : Auteur
Vincent Théry
  • Fonction : Auteur
Francis Giraud
  • Fonction : Auteur
Isabelle Abrunhosa-Thomas
Alain Artola
  • Fonction : Auteur
Fabrice Anizon
  • Fonction : Auteur
  • PersonId : 1109269
Radhouane Dallel
Pascale Moreau
  • Fonction : Auteur

Résumé

Mechanical Allodynia (MA), a frequent chronic pain symptom caused by innocuous stimuli, constitutes an unmet medical need, as treatments using analgesics available today are not always effective and can be associated with important side-effects. A series of 3,5-disubstituted pyridin-2(1H)-ones was designed, synthesized and evaluated in vivo toward a rat model of inflammatory MA. We found that the series rapidly and strongly prevented the development of MA. 3-(2-Bromophenyl)-5-(phenylamino)pyridin-2(1H)-one 69, the most active compound of the series, was also able to quickly reverse neuropathic MA in rats. Next, when 69 was evaluated toward a panel of 50 protein kinases (PK) in order to identify its potential biological target(s), we found that 69 is a p38a MAPK inhibitor, a PK known to contribute to pain hypersensitivity in animal models. 3,5-Disubstituted pyridin-2(1H)-ones thus could represent a novel class of analgesic for the treatment of MA.

Domaines

Neurobiologie

Dates et versions

hal-04487360 , version 1 (04-03-2024)

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Citer

Alexia Visseq, Amélie Descheemaeker, Nicolas Pinto-Pardo, Lionel Nauton, Vincent Théry, et al.. Pyridin-2(1H)one derivatives: A possible new class of therapeutics for mechanical allodynia. European Journal of Medicinal Chemistry, 2019, 187, pp.111917. ⟨10.1016/j.ejmech.2019.111917⟩. ⟨hal-04487360⟩

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