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Title: Synthesis and P1' SAR exploration of potent macrocyclic tissue factor-factor VIIa inhibitors

Selective tissue factor-factor VIIa complex (TF-FVIIa) inhibitors are viewed as promising compounds for treating thrombotic disease. In this contribution, we describe multifaceted exploratory SAR studies of S1'-binding moieties within a macrocyclic chemotype aimed at replacing cyclopropyl sulfone P1' group. Over the course of the optimization efforts, the 1-(1H-tetrazol-5-yl)cyclopropane P1' substituent emerged as an improved alternative, offering increased metabolic stability and lower clearance, while maintaining excellent potency and selectivity.
Authors:
 [1] ; ; ; ; ; ; ; ; ; ; ; ; ;
  1. (Uladzimir)
Publication Date:
OSTI Identifier:
1330868
Resource Type:
Journal Article
Resource Relation:
Journal Name: Bioorganic & Medicinal Chemistry Letters; Journal Volume: 26; Journal Issue: 20
Research Org:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org:
USDOE
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES