2. Academic Validation
  3. Quinazoline and phthalazine derivatives as novel melatonin receptor ligands analogues of agomelatine

Quinazoline and phthalazine derivatives as novel melatonin receptor ligands analogues of agomelatine

  • Eur J Med Chem. 2020 Mar 1;189:112078. doi: 10.1016/j.ejmech.2020.112078.
Raphaël Bolteau 1,  Florian Descamps 1,  Mohamed Ettaoussi 2,  Daniel H Caignard 3,  Philippe Delagrange 4,  Patricia Melnyk 1,  Saïd Yous 5
Affiliations

Affiliations

  • 1 Univ. Lille, Inserm, CHU Lille, UMR-S1172 - JPArc - Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer, F-59000, Lille, France.
  • 2 Univ. Lille, Inserm, CHU Lille, UMR-S1172 - JPArc - Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer, F-59000, Lille, France. Electronic address: m.ettaoussi@yahoo.fr.
  • 3 PEX Biotechnologie Chimie & Biologie, Institut de Recherches Servier, 78290, Croissy sur Seine, France; Institut de Recherches Internationales Servier, 92150, Suresnes, France.
  • 4 PEX Biotechnologie Chimie & Biologie, Institut de Recherches Servier, 78290, Croissy sur Seine, France.
  • 5 Univ. Lille, Inserm, CHU Lille, UMR-S1172 - JPArc - Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer, F-59000, Lille, France. Electronic address: said.yous@univ-lille2.fr.
PMID: 32004937 DOI: 10.1016/j.ejmech.2020.112078
Abstract

For further development of successors of Agomelatine through modulation of its pharmacokinetic properties, we report herein the design, synthesis and pharmacological results of a new family of Melatonin Receptor ligands. Issued from the introduction of quinazoline and phthalazine scaffolds carrying an ethyl amide lateral chain and a methoxy group as bioisosteric ligands analogues of previously developed Agomelatine. The biological activity of the prepared analogues was compared with that of Agomelatine. Quinazoline and phthalazine rings proved to be a versatile scaffold for easy feasible MT1 and MT2 ligands. Potent agonists with sub-micromolar binding affinity were obtained. However, the presence of two nitrogen atoms resulted in compounds with lower affinity for both MT1 and MT2, in comparison with the parent compound, balanced by the exhibition of good pharmacokinetic properties.

Keywords

Agomelatine; Agonist; MT(1); MT(2); Melatonin receptor; Phthalazine; Quinazoline.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z