Nonpeptide glycoprotein IIB/IIIA inhibitors. 19. A new design paradigm employing linearly minimized, centrally constrained, exosite inhibitors.

A new series of potent, linearly-minimized, orally active, selective GPIIb/ IIIa inhibitors is identified. Thus 15 (L-750,034) achieves interaction via a constrained, non-turned conformation that maintains the proper distance between its charged termini and full sulfonamide exosite interaction. The d iminutive stature and the proposed linear conformation of L-750,034 define a new paradigm for the conceptualization of RGD mimics. (C) 1999 Published by Elsevier Science Ltd. All rights reserved.