Discovery of CC-930, an orally active anti-fibrotic JNK inhibitor

  • Bioorg Med Chem Lett. 2012 Feb 1;22(3):1433-8. doi: 10.1016/j.bmcl.2011.12.027.
Véronique Plantevin Krenitsky  1 ,  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
Affiliations
  • 1. Celgene Corporation, 4550 Towne Centre Court, San Diego, CA 92121, USA. [email protected]
PMID: 22244937 DOI: 10.1016/j.bmcl.2011.12.027
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.

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