Exploratory solid-phase synthesis of factor Xa inhibitors: discovery and application of p3-heterocyclic amides as novel types of non-basic arginine su...

ID: ALA1131910

Journal: Bioorg Med Chem Lett

Title: Exploratory solid-phase synthesis of factor Xa inhibitors: discovery and application of p3-heterocyclic amides as novel types of non-basic arginine surrogates.

Authors: Ho JZ, Levy OE, Gibson TS, Nguyen K, Semple JE.

Abstract: 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.

CiteXplore: 10617091

DOI: 10.1016/s0960-894x(99)00628-9

Patent ID: ┄