Design and Synthesis of Novel Meta-Linked Phenylglycine Macrocyclic FVIIa Inhibitors.

ABSTRACT: Two novel series of meta-linked phenylglycine-based macrocyclic FVIIa inhibitors have been designed to improve the rodent metabolic stability and PK observed with the precursor para-linked phenylglycine macrocycles. Through iterative structure-based design and optimization, the TF/FVIIa K_i was improved to subnanomolar levels with good clotting activity, metabolic stability, and permeability.

SUBMITTER: Richter JM 

PROVIDER: S-EPMC5238462 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature