作者
Véronique Plantevin Krenitsky,Lisa Nadolny,Mercedes Delgado,Leticia Ayala,Steven S. Clareen,Robert Hilgraf,Ronald Albers,Sayee G. Hegde,Neil D’Sidocky,John Sapienza,Jonathan Wright,Meg McCarrick,Sogole Bahmanyar,Philip P. Chamberlain,S.L. Delker,Jeff Muir,David A. Giegel,Li Xu,Maria Celeridad,Jeff Lachowitzer,Brydon L. Bennett,Mehran F. Moghaddam,Oleg G. Khatsenko,Jason D. Katz,R. Fan,April Bai,Yang Tang,Michael A. Shirley,Brent Benish,T. Bodine,Kate Blease,Heather K. Raymon,Brian E. Cathers,Yoshitaka Satoh
摘要
In this Letter we describe the discovery of potent, selective, and orally active aminopurine JNK inhibitors. Improving the physico-chemical properties as well as increasing the potency and selectivity of a subseries with rat plasma exposure, led to the identification of four structurally diverse inhibitors. Differentiation based on PK profiles in multiple species as well as activity in a chronic efficacy model led to the identification of 1 (CC-930) as a development candidate, which is currently in Phase II clinical trial for IPF.