Non-peptide glycoprotein IIb/IIIa inhibitors. 6. Design and synthesis of rigid, centrally constrained non-peptide fibrinogen receptor antagonists

✍ Scribed by B.C. Askew; C.J. McIntyre; C.A. Hunt; D.A. Claremon; R.J. Gould; R.J. Lynch; D.J. Armstrong

• Book ID: 103982847
• Publisher: Elsevier Science
• Year: 1995
• Tongue: English
• Weight: 295 KB
• Volume: 5
• Category: Article
• ISSN: 0960-894X
• DOI: 10.1016/0960-894x(95)00057-z

✦ Synopsis

Low molecular weight non-peptide inhibitors of platelet aggregation based on rigid bicyclic scaffolds are described. Consideration of the reported conformational preferences of 1-alkyl-3-carbonyl pyrroles led to the synthesis of pyrrolopiperazinone 2a which was shown to be a potent, selective antagonist.

The activation, adherence, and subsequent aggregation of circulating platelets has been shown to play an important role in various vasoocculsive disorders such as unstable angina, myocardial infarction, transient ischemic attacks, and stroke. 1 The final, common pathway for platelet aggregation, regardless of the activating signal, is the binding of fibrinogen by glycoprotein IIb/IIIa (GPIIb/IIIa) on the surface of activated platelets. 2 This binding is mediated in part by Arg-Gly-Asp (RGD) sequences present in fibrinogen, therefore, small molecules and peptidomemetics that feature elements of this tripeptide sequence have been pursued as inhibitors of platelet aggregation. 3 Several groups have reported compounds that incorporate rigid central