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Acyclic cyanamide-based inhibitors of cathepsin K |
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| Authors: | Barrett David G Deaton David N Hassell Anne M McFadyen Robert B Miller Aaron B Miller Larry R Payne J Alan Shewchuk Lisa M Willard Derril H Wright Lois L |
| Affiliation: | Department of Medicinal Chemistry, GlaxoSmithKline, Research Triangle Park, NC 27709, USA. |
| Abstract: | Conversion of the proline-derived cyanamide lead to an acyclic cyanamide capable of forming an additional hydrogen bond with cathepsin K resulted in a large increase in inhibitory activity. An X-ray structure of a co-crystal of a cyanamide with cathepsin K confirmed the enzyme interaction. Furthermore, a representative acyclic cyanamide inhibitor 6r was able to attenuate bone resorption in the rat calvarial model. |
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