In vitro and in vivo evaluation of 6-aminopyrazolyl-pyridine-3-carbonitriles as JAK2 kinase inhibitors

Tao Wang; Stephanos Ioannidis; Lynsie Almeida; Michael H Block; Audrey M Davies; Michelle L Lamb; David A Scott; Mei Su; Hai-Jun Zhang; Marat Alimzhanov; Geraldine Bebernitz; Kirsten Bell; Michael Zinda

doi:10.1016/j.bmcl.2011.03.053

In vitro and in vivo evaluation of 6-aminopyrazolyl-pyridine-3-carbonitriles as JAK2 kinase inhibitors

Bioorg Med Chem Lett. 2011 May 15;21(10):2958-61. doi: 10.1016/j.bmcl.2011.03.053. Epub 2011 Mar 21.

Authors

Tao Wang¹, Stephanos Ioannidis, Lynsie Almeida, Michael H Block, Audrey M Davies, Michelle L Lamb, David A Scott, Mei Su, Hai-Jun Zhang, Marat Alimzhanov, Geraldine Bebernitz, Kirsten Bell, Michael Zinda

Affiliation

¹ Department of Cancer Chemistry, Oncology Innovative Medicines Unit, AstraZeneca R&D Boston, 35 Gatehouse Drive, Waltham, MA 02451, USA. [email protected]

PMID: 21493067
DOI: 10.1016/j.bmcl.2011.03.053

Abstract

Synthesis and biological evaluation of a series of 6-aminopyrazolyl-pyridine-3-carbonitriles as JAK2 kinase inhibitors was reported. Biochemical screening, followed by profile optimization, resulted in JAK2 inhibitors exhibiting good kinase selectivity, pharmacokinetic properties, physical properties and pharmacodynamic effects.

MeSH terms

Animals
Cell Line
Cell Proliferation / drug effects
Inhibitory Concentration 50
Janus Kinase 2 / antagonists & inhibitors*
Mice
Molecular Structure
Nitriles / chemical synthesis*
Nitriles / chemistry
Nitriles / pharmacokinetics
Nitriles / pharmacology*
Protein Kinase Inhibitors / chemistry*
Protein Kinase Inhibitors / pharmacokinetics
Protein Kinase Inhibitors / pharmacology*
Pyrazoles / chemistry*
Pyridines / chemistry*
Rats
Structure-Activity Relationship

Substances

Nitriles
Protein Kinase Inhibitors
Pyrazoles
Pyridines
Janus Kinase 2