Bioorganic & Medicinal Chemistry Letters 2005-10-01

Acetylenic TACE inhibitors. Part 2: SAR of six-membered cyclic sulfonamide hydroxamates.

J I Levin, J M Chen, L M Laakso, M Du, X Du, A M Venkatesan, V Sandanayaka, A Zask, J Xu, W Xu, Y Zhang, J S Skotnicki

Index: Bioorg. Med. Chem. Lett. 15 , 4345-9, (2005)

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Abstract

The SAR of a series of potent sulfonamide hydroxamate TACE inhibitors bearing a butynyloxy P1' group was explored. In particular, compound 5k has excellent in vitro potency against TACE enzyme and in cells, and oral activity in an in vivo model of TNF-alpha production and a collagen-induced arthritis model.