Author/Authors :
William J. Hoekstra، نويسنده , , Bruce E. Maryanoff، نويسنده , , Patricia Andrade-Gordon، نويسنده , , Judith H. Cohen، نويسنده , , Michael J. Costanzo، نويسنده , , Bruce P. Damiano، نويسنده , , Barbara J. Haertlein، نويسنده , , Bruce D. Harris، نويسنده , , Jack A. Kauffman، نويسنده , , Patricia M. Keane، نويسنده , , David F. McComsey، نويسنده , , Frank J. Villani Jr.، نويسنده , , Stephen C. Yabut، نويسنده ,
Abstract :
A study of β-turn peptide mimetics, related to the C-terminal γ-chain of fibrinogen and containing a nipecotic acid scaffold, led to RWJ-50042 (1), an interesting fibrinogen receptor (GPIIb/IIIa) antagonist. To enhance potency, we employed solid-phase parallel synthesis for the preparation of over 200 analogues in a protocol of optimization cycles. This strategy produced several promising nipecotamide analogues, such as 25, which is 35 times more potent than 1 in vitro.
