Discovery of an Orally Active Series of Isoxazoline Glycoprotein IIb/IIIa Antagonists
Journal of Medicinal Chemistry1997Vol. 40(13), pp. 2064–2084
Citations Over TimeTop 11% of 1997 papers
Chu‐Biao Xue, John Wityak, Thais M. Sielecki, Donald Pinto, Douglas G. Batt, Gary A. Cain, Michael Sworin, Arlene L. Rockwell, John Roderick, Shuaige Wang, Michael J. Orwat, William E. Frietze, Lori L. Bostrom, Jie Liu, C. Anne Higley, F. Wayne Rankin, A. Ewa Tobin, George Emmett, George K. Lalka, Jean Y. Sze, Susan V. Di Meo, Shaker A. Mousa, Martin Thoolen, Adrienne L. Racanelli, Elizabeth A. Hausner, Thomas M. Reilly, William F. DeGrado, Ruth R. Wexler, Richard E. Olson
Abstract
Using isoxazoline XR299 (1a) as a starting point for the design of highly potent, long-duration GPIIb/IIIa antagonists, the effect of placing lipophilic substituents at positions alpha and beta to the carboxylate moiety was evaluated. Of the compounds studied, it was found that the n-butyl carbamate 24u exhibited superior potency and duration of ex vivo antiplatelet effects in dogs. Replacement of the benzamidin-4-yl moiety with alternative basic groups, elimination of the isoxazoline stereocenter, and reversal of the orientation of the isoxazoline ring resulted in lowered potency and/or duration of action.
Related Papers
- → Optimization of a 1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione series of HIV capsid assembly inhibitors 2: Structure–activity relationships (SAR) of the C3-phenyl moiety(2013)21 cited
- → Diastereo- and enantioselective synthesis of a conagenin skeletal amide moiety(2004)8 cited
- → Pre-clinical to clinical potency of AZD7624 in LPS induced TNFa response(2015)
- → The First Total Synthesis of Tanzawaic Acid B(2022)
- → The First Total Synthesis of Tanzawaic Acid B(2023)