Non-peptide GPIIb/IIIa inhibitors. 20. Centrally constrained thienothiophene α-sulfonamides are potent, long acting in vivo inhibitors of platelet aggregation

…, GD Hartman, CF Homnick, MA Holahan…

Index: Egbertson, Melissa S.; Cook, Jacquelynn J.; Bednar, Bohumil; Prugh, John D.; Bednar, Rodney A.; Gaul, Stanley L.; Gould, Robert J.; Hartman, George D.; Homnick, Carl F.; Holahan, Marie A.; Libby, Laura A.; Lynch Jr., Joseph J.; Lynch, Robert J.; Sitko, Gary R.; Stranieri, Maria T.; Vassallo, Laura M. Journal of Medicinal Chemistry, 1999 , vol. 42, # 13 p. 2409 - 2421

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Citation Number: 46

Abstract

The synthesis and pharmacology of 4, a potent thienothiophene non-peptide fibrinogen receptor antagonist, are reported. Compound 4 inhibited the aggregation of human gel- filtered platelets with an IC50 of 8 nM and demonstrated an 8-fold improvement in affinity for isolated GPIIb/IIIa receptors over analogues possessing an isoindolinone backbone. Flow cytometry studies revealed that the binding of 4 to resting platelets is a diffusion-controlled ...