1.
Bioorg Med Chem Lett
; 25(14): 2809-12, 2015 Jul 15.
Article
in English
| MEDLINE
| ID: mdl-25987372
ABSTRACT
The discovery, synthesis, and characterization of 9H-carbazole-1-carboxamides as potent and selective ATP-competitive inhibitors of Janus kinase 2 (JAK2) are discussed. Optimization for JAK family selectivity led to compounds 14 and 21, with greater than 45-fold selectivity for JAK2 over all other members of the JAK kinase family.
Subject(s)
Amides/chemistry , Janus Kinase 2/antagonists & inhibitors , Protein Kinase Inhibitors/chemistry , Amides/metabolism , Amides/pharmacology , Binding Sites , Carbazoles/chemistry , Cell Line, Tumor , Cell Proliferation/drug effects , Crystallography, X-Ray , Humans , Janus Kinase 1/antagonists & inhibitors , Janus Kinase 1/metabolism , Janus Kinase 2/metabolism , Janus Kinase 3/antagonists & inhibitors , Janus Kinase 3/metabolism , Molecular Dynamics Simulation , Protein Binding , Protein Kinase Inhibitors/metabolism , Protein Kinase Inhibitors/pharmacology , Protein Structure, Tertiary , Structure-Activity Relationship
2.
Bioorg Med Chem Lett
; 21(5): 1425-8, 2011 Mar 01.
Article
in English
| MEDLINE
| ID: mdl-21282055
ABSTRACT
SAR studies of pyrrolo[1,2-f]triazines as JAK2 inhibitors is presented. Achieving JAK2 inhibition selectively over JAK3 is discussed.