| Literature DB >> 22244937 |
Véronique Plantevin Krenitsky1, Lisa Nadolny, Mercedes Delgado, Leticia Ayala, Steven S Clareen, Robert Hilgraf, Ronald Albers, Sayee Hegde, Neil D'Sidocky, John Sapienza, Jonathan Wright, Meg McCarrick, Sogole Bahmanyar, Philip Chamberlain, Silvia L Delker, Jeff Muir, David Giegel, Li Xu, Maria Celeridad, Jeff Lachowitzer, Brydon Bennett, Mehran Moghaddam, Oleg Khatsenko, Jason Katz, Rachel Fan, April Bai, Yang Tang, Michael A Shirley, Brent Benish, Tracey Bodine, Kate Blease, Heather Raymon, Brian E Cathers, Yoshitaka Satoh.
Abstract
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.Entities:
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Year: 2011 PMID： 22244937 DOI： 10.1016/j.bmcl.2011.12.027
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823