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Synthesis and SAR of Thrombin Inhibitors Incorporating a Novel 4-Amino-Morpholinone Scaffold: Analysis of X-ray Crystal Structure of Enzyme Inhibitor Complex

✍ Scribed by Nilsson, Jonas W.; Kvarnström, Ingemar; Musil, Djordje; Nilsson, Ingemar; Samulesson, Bertil


Book ID
121242303
Publisher
American Chemical Society
Year
2003
Tongue
English
Weight
636 KB
Volume
46
Category
Article
ISSN
0022-2623

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An indolizidinone motif with strategically placed substitutents was designed and synthesized as a constrained mimic of D-Phe-Pro-Arg. Low nanomolar inhibition of alpha-thrombin validates the design elements in this inhibitor which also exhibits a 20-fold selectivity for thrombin versus trypsin. An X