Discovery of pyrazol-3-ylamino pyrazines as novel JAK2 inhibitors.
The design, synthesis and biological evaluation of a series of pyrazol-3-ylamino pyrazines as potent and selective JAK2 kinase inhibitors is reported, along with the pharmacokinetic and pharmacodynamic properties of lead compounds.
Ioannidis
Stephanos
S
Department of Cancer Chemistry, AstraZeneca R&D Boston, Waltham, MA 02451, USA. Stephanos.Ioannidis@astrazeneca.com
Lamb
Michelle L
ML
Davies
Audrey M
AM
Almeida
Lynsie
L
Su
Mei
M
Bebernitz
Geraldine
G
Ye
Minwei
M
Bell
Kirsten
K
Alimzhanov
Marat
M
Zinda
Michael
M
D000818:Animals; D004285:Dogs; D055808:Drug Discovery; D006801:Humans; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors*; D051379:Mice; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011719:Pyrazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D047428:Protein Kinase Inhibitors; D011719:Pyrazines; D011720:Pyrazoles; D053614:Janus Kinase 2