167854-05-9Relevant articles and documents
Preparation and biological activity of novel tricyclic GPIIb/IIIa antagonists
Robarge, Kirk D.,Dina, Michael S.,Somers, Todd C.,Lee, Arthur,Rawson, Thomas E.,Olivero, Alan G.,Tischler, Maureen H.,Webb II, Robert R.,Weese, Kenneth J.,Aliagas, Ignacio,Blackburn, Brent K.
, p. 2345 - 2381 (1998)
Antagonists of the glycoprotein GPIIb/IIIa are a promising class of antithrombotic agents offering potential advantages over present antiplatelet agents (i.e., aspirin and ticlopidine). Novel tricyclic nonpeptidal GPIIb/IIIa antagonists have been prepared and evaluated in vitro as antagonists of fibrinogen binding to the purified GPIIb/IIIa receptor and as inhibitors of platelet aggregation. The work presented demonstrates the robustness of the benzodiazepinedione (BZDD) scaffold, which can be functionalized at the N1-C2 amide as well as at C7, to provide structural diversity and allow optimization of the physiochemical and pharmacological properties of the BZDD based GPIIb/IIIa antagonists. In addition, the resulting new class of tricyclic GPIIb/IIIa antagonists could be used to probe for additional binding interactions on the GPIIb/IIIa receptor and perhaps lead to BZDD based GPIIb/IIIa antagonists with increased potency. The tricyclic molecules reported herein demonstrate that a heterocyclic ring can be fused to the benzodiazepinedione scaffold with retention of anti-aggregatory potency and in the case of tetrazole 30i, increased potency relative to the bicyclic analogue 1c. Copyright (C) 1998 Elsevier Science Ltd.
