Design,synthesis and biological activity of novel non-amidine factor Xa inhibitors. Part 1: P(1) structure-activity relationships of the substituted 1-(2-Naphthyl)-1H-pyrazole-5-carboxylamides |
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| Authors: | Jia Zhaozhong J Wu Yanhong Huang Wenrong Goldman Erick Zhang Penglie Woolfrey John Wong Paul Huang Brian Sinha Uma Park Gary Reed Andrea Scarborough Robert M Zhu Bing-Yan |
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| Institution: | Medicinal Chemistry Department, Millennium Pharmaceuticals, Inc., 256 East Grand Ave, South San Francisco, CA 94080, USA. zhaozhong.jia@mpi.com |
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| Abstract: | Based on DuPont Pharmaceuticals' monobenzamidine lead structure SN429, we have designed the biphenyl 1-(2-naphthyl)-1H-pyrazole-5-carboxylamides as a novel series of non-basic factor Xa inhibitors. We have discovered that the displacement of the benzamidine moiety with substituted 2-naphthyl structures not only results in highly potent factor Xa inhibitors, but also significantly increases their enzyme specificity and oral bioavailability. |
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