Exploratory solid-phase synthesis of factor Xa inhibitors: Discovery and application of P3-heterocyclic amides as novel types of non-basic arginine surrogates

Article abstract of DOI:10.1016/S0960-894X(99)00628-9

A series of novel FXa inhibitors 2a-m and 3a-f was discovered that feature heterocyclic carboxamides tethered to a d-diaminobutyric acid sidechain. These neutral amide derivatives serve as novel P₃ d-arginine mimics. Pyrazine carboxamide scaffolds afforded the most potent FXa inhibitors (e.g., 2b IC₅₀ = 4.6 nM). The synthesis and biological activity of two focused libraries are reported.