A novel chemotype of kinase inhibitors: Discovery of 3,4-ring fused 7-azaindoles and deazapurines as potent JAK2 inhibitors

Tiansheng Wang; Mark W Ledeboer; John P Duffy; Francesco G Salituro; Albert C Pierce; Harmon J Zuccola; Eric Block; Dina Shlyakter; James K Hogan; Youssef L Bennani

doi:10.1016/j.bmcl.2009.11.021

A novel chemotype of kinase inhibitors: Discovery of 3,4-ring fused 7-azaindoles and deazapurines as potent JAK2 inhibitors

Bioorg Med Chem Lett. 2010 Jan 1;20(1):153-6. doi: 10.1016/j.bmcl.2009.11.021. Epub 2009 Nov 12.

Authors

Tiansheng Wang¹, Mark W Ledeboer, John P Duffy, Francesco G Salituro, Albert C Pierce, Harmon J Zuccola, Eric Block, Dina Shlyakter, James K Hogan, Youssef L Bennani

Affiliation

¹ Vertex Pharmaceuticals Inc., 130 Waverly St., Cambridge, MA 02139-4242, United States. tiansheng_wang@vrtx.com

PMID: 19945871
DOI: 10.1016/j.bmcl.2009.11.021

Abstract

Pictet-Spengler condensation of aldehydes or alpha-keto-esters with 4-(2-anilinophenyl)-7-azaindole (11) or deazapurine (12) gave high yields of the 3,4-fused cyclic compounds. SAR studies, by varying the substituted benzaldehyde components, lead to the discovery of a series of potent JAK2 kinase inhibitors.

MeSH terms

Benzaldehydes / chemistry
Binding Sites
Cell Line
Crystallography, X-Ray
Drug Discovery
Humans
Indoles / chemistry*
Janus Kinase 2 / antagonists & inhibitors*
Janus Kinase 2 / metabolism
Protein Kinase Inhibitors / chemical synthesis
Protein Kinase Inhibitors / chemistry*
Protein Kinase Inhibitors / pharmacology
Purines / chemistry*
Structure-Activity Relationship

Substances

7-azaindole dimer
Benzaldehydes
Indoles
Protein Kinase Inhibitors
Purines
Janus Kinase 2
benzaldehyde