Solid-phase parallel synthesis applied to lead optimization: Discovery of potent analogues of the GPIIb/IIIa antagonist RWJ-50042

Article abstract of DOI:10.1016/0960-894X(96)00438-6

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.