Discovery and SAR of potent, orally available 2,8-diaryl-quinoxalines as a new class of JAK2 inhibitors.
We have designed and synthesized a novel series of 2,8-diaryl-quinoxalines as Janus kinase 2 inhibitors. Many of the inhibitors show low nanomolar activity against JAK2 and potently suppress proliferation of SET-2 cells in vitro. In addition, compounds from this series have favorable rat pharmacokinetic properties suitable for in vivo efficacy evaluation.
Novartis Institutes for Biomedical Research, Novartis Pharma AG, WKL-136.4.96, CH-4002 Basel, Switzerland. carole.pissot@novartis.com
Carole
C
Pissot-Soldermann
Marc
M
Gerspacher
Pascal
P
Furet
Christoph
C
Gaul
Philipp
P
Holzer
Clive
C
McCarthy
Thomas
T
Radimerski
Catherine H
CH
Regnier
Fabienne
F
Baffert
Peter
P
Drueckes
Gisele A
GA
Tavares
Eric
E
Vangrevelinghe
Francesca
F
Blasco
Giorgio
G
Ottaviani
Flavio
F
Ossola
Julien
J
Scesa
Janitha
J
Reetz
D000284:Administration, Oral; D000818:Animals; D002460:Cell Line; D055808:Drug Discovery; D004353:Drug Evaluation, Preclinical; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D011810:Quinoxalines / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship
D047428:Protein Kinase Inhibitors; D011810:Quinoxalines; C507927:Jak2 protein, rat; D053614:Janus Kinase 2