Letters in Drug Design & Discovery

G. Perry
University of Texas
San Antonio, TX
Email: lddd@benthamscience.org


Design and Synthesis of 3-Arylisoxazoline-5-Carboxamide and 3-Arylisoxazoline-5-Acetamide Libraries as Potential Factor Xa Inhibitors

Author(s): John F. Quinn, Brian T. Gregg, Douglas B. Kitchen, Robert M. Lewis, Dana A. Razzano, Lauren E. Kayser, Levon J. Schilling, Kathryn C. Golden.


Two synthetic libraries based on a core isoxazoline motif have been designed and prepared specifically to probe the S1 and S4 binding pockets of the Factor Xa enzyme active sites. A highly efficient parallel solution phase synthetic method resulted in the synthesis of 3-arylisoxazoline-5-carboxamides and 3-arylisoxazoline-5-acetamides libraries yielding 192 compounds in total. Highlights of this work include preparation of the isoxazoline cores via a [3+2] cycloaddition between oximes with acrylates or vinyl acetates and the use of activated p-nitrophenyl esters for ease of amide formation and reaction purification.

Keywords: Arylisoxazolines, Docking, Factor Xa, Glide, Library synthesis, Thromboembolic diseases, isoxazoline, nitrophenyl, acrylates, warfarin, hemostatic, Thromboembolic, SCAFFOLDS, stereocenters, caboxylates

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Article Details

Year: 2012
Page: [2 - 7]
Pages: 6
DOI: 10.2174/157018012798193035