… Introduction of the amide moiety into the 12-membered macrocyclic linker 22 increased the
… The amide moiety, which led to a significant improvement in terms of both FXIa activity and …

… inhibitors with cyclic P1 linkers was designed based on the X-ray crystal structure of 1. By
constraining the P1 linker … , while removing the tetrazole moiety and acrylamide proton, both …

… , between the NH of the amide moiety in the macrocyclic linker and the carbonyl of Leu41 in
… that the alkyl backbone of the macrocyclic amide linker did not fully access the hydrophobic …

… The m-chlorophenyl P1 moiety is orthogonal to the urea linker, with the urea carbonyl oriented
directly into the oxyanion hole and capable of forming strong hydrogen bond interactions …

… We then focused on the linker between the S1β and the prime site with an aim to enhance
… of a polar moiety could introduce additional conformational bias in the linker and lower the …

… We also show that certain related linkers, eg, more rigid, aromatic linkers, are not preferred,
which points to the interesting landscape of heparin-binding site of hFXIa. Overall, this work …

… Since efforts to reduce PSA in the P2 prime region led to a loss in both FXIa affinity and
metabolic stability, we turned our attention to modifying the amide moiety in the macrocyclic linker…

… Oral factor XIa (FXIa) inhibitors may provide a promising new … cyclic carbamate P1 linker
which provided improved oral … imidazole core as well as various linkers to the P1 group led …

… moiety on an otherwise identical base scaffold. Both inhibitors contain a minimum of 10
linker atoms, yet the additional triazole of 28S is likely to impart significant rigidity to the linker in …

… triazole moiety as a privileged scaffold in the interval linker for … By switching the alkyl linker
to PEG and other linkers, other … inhibitors coupled with the thalidomide family moiety were …