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SAR studies of non-zinc-chelating MMP-13 inhibitors: improving selectivity and metabolic stability
Donghong Amy Gao1, Zhaoming Xiong, Alexander Heim-Riether
1Department of Medicinal Chemistry, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT 06877, USA. amy.gao@boehringer-ingelheim.com
Bioorganic & Medicinal Chemistry Letters
|August 3, 2010
Abstract:
SAR studies to improve the selectivity and metabolic stability of a class of recently discovered MMP-13 inhibitors are reported. Improved selectivity was achieved by modifying interactions with the S1' pocket. Metabolic stability was improved through reduction of inhibitor lipophilicity. This translated into lower in vivo clearance for the preferred compound.
