text: Discovery of a series of novel 5H-pyrrolo[2,3-b]pyrazine-2-phenyl ethers, as potent JAK3 kinase inhibitors.
  We report the discovery of a novel series of ATP-competitive Janus kinase 3 (JAK3) inhibitors based on the 5H-pyrrolo[2,3-b]pyrazine scaffold. The initial leads in this series, compounds 1a and 1h, showed promising potencies, but a lack of selectivity against other isoforms in the JAK family. Computational and crystallographic analysis suggested that the phenyl ether moiety possessed a favorable vector to achieve selectivity. Exploration of this vector resulted in the identification of 12b and 12d, as potent JAK3 inhibitors, demonstrating improved JAK family and kinase selectivity.
entities.id: T10 T11 T1 T2 T3 T4 T5 T6 T7 T8 T9
entities.type: GENE-Y GENE-N CHEMICAL CHEMICAL CHEMICAL GENE-N GENE-Y GENE-N GENE-N GENE-Y GENE-Y
entities.text: JAK3 kinase 5H-pyrrolo[2,3-b]pyrazine ATP 5H-pyrrolo[2,3-b]pyrazine-2-phenyl ethers JAK JAK3 JAK kinase Janus kinase 3 JAK3