Naphthyl ketones: a new class of Janus kinase 3 inhibitors.
Potent inhibition of Janus kinase 3 was found for a series of naphthyl(beta-aminoethyl)ketones (e.g. 7, pIC50 = 7.1+/-0.3). Further studies indicated that these compounds fragment in less than 1 h by retro-Michael reaction in the Jak3 in vitro ELISA assay procedure. The breakdown product of 7, 2-naphthylvinyl ketone (22, pIC50 = 6.8+/-0.3) showed very similar inhibitory activity to 7. Compounds 7 (in neutral buffer) and 22 will be useful pharmacological tools for the investigation of the Janus tyrosine kinase Jak3.
Brown
G R
GR
Respiratory & Inflammation Research, AstraZeneca, Macclesfield, Cheshire, UK. george.r.brown@astrazeneca.com
Bamford
A M
AM
Bowyer
J
J
James
D S
DS
Rankine
N
N
Tang
E
E
Torr
V
V
Culbert
E J
EJ
D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007202:Indicators and Reagents; D053616:Janus Kinase 3; D007659:Ketones / Q000138:chemical synthesis* / Q000494:pharmacology; D008352:Mannich Bases; D009281:Naphthalenes / Q000138:chemical synthesis* / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D007659:Ketones; D008352:Mannich Bases; D009281:Naphthalenes; D011505:Protein-Tyrosine Kinases; C507933:JAK3 protein, human; D053616:Janus Kinase 3