Naphthyl ketones: a new class of Janus kinase 3 inhibitors

  • Bioorg Med Chem Lett. 2000 Mar 20;10(6):575-9. doi: 10.1016/s0960-894x(00)00051-2.
G R Brown  1 ,  A M Bamford ,  J Bowyer ,  D S James ,  N Rankine ,  E Tang ,  V Torr ,  E J Culbert
Affiliations
  • 1. Respiratory & Inflammation Research, AstraZeneca, Macclesfield, Cheshire, UK. [email protected]
PMID: 10741557 DOI: 10.1016/s0960-894x(00)00051-2
Abstract

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.

Products