203934-64-9Relevant academic research and scientific papers
Substituted pyrrolidine hydroxamate metalloprotease inhibitors
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, (2008/06/13)
The invention provides compounds which are potent inhibitors of metalloproteases and which are effective in treating conditions characterized by excess activity of these enzymes. In particular, the present invention relates to compounds having a structure
Design, synthesis, and biological evaluation of matrix metalloproteinase inhibitors derived from a modified proline scaffold
Cheng, Menyan,De, Biswanath,Almstead, Neil G.,Pikul, Stanislaw,Dowty, Martin E.,Dietsch, Charles R.,Dunaway, C. Michelle,Gu, Fei,Hsieh, Lily C.,Janusz, Michael J.,Taiwo, Yetunde O.,Natchus, Michael G.,Hudlicky, Tomas,Mandel, Martin
, p. 5426 - 5436 (2007/10/03)
The synthesis and structure-activity relationship (SAR) studies of a series of proline-based matrix metalloproteinase inhibitors are described. The data reveal a remarkable potency enhancement in those compounds that contain an sp2 center at the C-4 carbon of the ring relative to similar, saturated compounds. This effect was noted in compounds that contained a functionalized oxime moiety or an exomethylene at C-4, and the potencies were typically 3 hybridization and the effect was typically an order of magnitude loss in potency. A comparison of compounds 14 and 34 exemplifies this observation. An X-ray structure was obtained for a stromelysin-inhibitor complex which provided insights into the SAR and selectivity trends observed within the series. In vitro intestinal permeability data for many compounds was also accumulated.
