Synthesis of new dipyrrolo- and furopyrrolopyrazinones related to tripentones and their biological evaluation as potential kinases (CDKs1-5, GSK-3) inhibitors.
We herein describe the synthesis of novel dipyrrolo- and furopyrrolopyrazinones related to highly cytotoxic tripentones and to their oximes. The synthetic pathway involved in particular a Curtius rearrangement and a subsequent cyclisation into the title pyrazinones. The biological evaluation towards various cyclin-dependent kinases (CDKs1-5, GSK-3) highlighted a weak inhibitory activity for the oximes whose SAR was studied by a molecular modeling study.
Rochais
Christophe
C
Centre d'Etudes et de Recherche sur le Médicament de Normandie, U.F.R. des Sciences Pharmaceutiques, Université de Caen Basse-Normandie, 5 rue Vaubénard, 14032 Caen cedex, France.
Duc
Nghia Vu
NV
Lescot
Elodie
E
Sopkova-de Oliveira Santos
Jana
J
Bureau
Ronan
R
Meijer
Laurent
L
Dallemagne
Patrick
P
Rault
Sylvain
S
D000818:Animals; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D003500:Cyclization; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors*; D006801:Humans; D007659:Ketones; D008958:Models, Molecular; D010091:Oximes; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D011719:Pyrazines / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D007659:Ketones; D010091:Oximes; D047428:Protein Kinase Inhibitors; D011719:Pyrazines; D018844:Cyclin-Dependent Kinases; D038362:Glycogen Synthase Kinase 3