title: In vitro and in vivo evaluation of 6-aminopyrazolyl-pyridine-3-carbonitriles as JAK2 kinase inhibitors.
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.
authors.affiliation: Department of Cancer Chemistry, Oncology Innovative Medicines Unit, AstraZeneca R&D Boston, 35 Gatehouse Drive, Waltham, MA 02451, USA. tao.wang@astrazeneca.com
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Stephanos
authors.initials: S
authors.lastname: Ioannidis
authors.forename: Lynsie
authors.initials: L
authors.lastname: Almeida
authors.forename: Michael H
authors.initials: MH
authors.lastname: Block
authors.forename: Audrey M
authors.initials: AM
authors.lastname: Davies
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Lamb
authors.forename: David A
authors.initials: DA
authors.lastname: Scott
authors.forename: Mei
authors.initials: M
authors.lastname: Su
authors.forename: Hai-Jun
authors.initials: HJ
authors.lastname: Zhang
authors.forename: Marat
authors.initials: M
authors.lastname: Alimzhanov
authors.forename: Geraldine
authors.initials: G
authors.lastname: Bebernitz
authors.forename: Kirsten
authors.initials: K
authors.lastname: Bell
authors.forename: Michael
authors.initials: M
authors.lastname: Zinda
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D020128:Inhibitory Concentration 50; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors*; D051379:Mice; D015394:Molecular Structure; D009570:Nitriles / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D011720:Pyrazoles / Q000737:chemistry*; D011725:Pyridines / Q000737:chemistry*; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D009570:Nitriles; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011725:Pyridines; D053614:Janus Kinase 2