Synthesis and preliminary in vitro kinase inhibition evaluation of new diversely substituted pyrido[3,4-g]quinazoline derivatives.

Wael Zeinyeh (1) , Yannick J. Esvan (1) , Lionel Nauton (1) , Nadège Loaëc (2) , Laurent Meijer (2) , Vincent Théry (1) , Fabrice Anizon (1) , Francis Giraud (1) , Pascale Moreau (1)

1 ICCF - Institut de Chimie de Clermont-Ferrand
2 ManRos Therapeutics

The synthesis of new diversely substituted pyrido[3,4-g]quinazolines is described. The inhibitory potencies of prepared compounds toward a panel of five CMGC protein kinases (CDK5, CLK1, DYRK1A, CK1, GSK3), that are known to play a potential role in Alzheimer’s disease, were evaluated. The best overall kinase inhibition profile was found for nitro compound 4 bearing an ethyl group at the 5-position.

Mots clés: Pyrido[3; 4-g]quinazoline; Protein kinase inhibition; CLK1; DYRK1A; CDK5; GSK3; CK1

Domaines: Chimie

Wael Zeinyeh, Yannick J. Esvan, Lionel Nauton, Nadège Loaëc, Laurent Meijer, et al.. Synthesis and preliminary in vitro kinase inhibition evaluation of new diversely substituted pyrido[3,4-g]quinazoline derivatives. . Bioorganic and Medicinal Chemistry Letters, 2016, 26, pp.4327-4329. ⟨10.1016/j.bmcl.2016.07.032⟩. ⟨hal-01367659⟩