Aminopurine based JNK inhibitors for the prevention of ischemia reperfusion injury

作者:Krenitsky Veronique Plantevin*; Delgado Mercedes; Nadolny Lisa; Sahasrabudhe Kiran; Ayala Leticia; Clareen Steven S; Hilgraf Robert; Albers Ronald; Kois Adam; Hughes Kevin; Wright Jonathan; Nowakowski Jacek; Sudbeck Elise; Ghosh Sutapa; Bahmanyar Sogole; Chamberlain Philip; Muir Jeff; Cathers Brian E; Giegel David; Xu Li; Celeridad Maria; Moghaddam Mehran; Khatsenko Oleg; Omholt Paul; Katz Jason; Pai Sema; Fan Rachel; Tang Yang; Shirley Michael A; Benish Brent
来源:Bioorganic & Medicinal Chemistry Letters, 2012, 22(3): 1427-1432.
DOI:10.1016/j.bmcl.2011.12.028

摘要

In this Letter we describe the optimization of an aminopurine lead (1) with modest potency and poor overall kinase selectivity which led to the identification of a series of potent, selective JNK inhibitors. Improvement in kinase selectivity was enabled by introduction of an aliphatic side chain at the C-2 position. CC-359 (2) was selected as a potential clinical candidate for diseases manifested by ischemia reperfusion injury.

  • 出版日期2012-2-1