Bioorganic & Medicinal Chemistry Letters 1999-03-22

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

G D Hartman, M E Duggan, W F Hoffman, R J Meissner, J J Perkins, A E Zartman, A M Naylor-Olsen, J J Cook, J D Glass, R J Lynch, G Zhang, R J Gould

Index: Bioorg. Med. Chem. Lett. 9(6) , 863-8, (1999)

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Abstract

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 diminutive stature and the proposed linear conformation of L-750,034 define a new paradigm for the conceptualization of RGD mimics.