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Updated: Mar 15, 2026

Functionalized Spirocyclic Heterocycle Synthesis and Cytotoxicity Assay
Published on: February 9, 2021
Synthesis and P1' SAR exploration of potent macrocyclic tissue factor-factor VIIa inhibitors
Vladimir Uladzimir Ladziata1, Peter W Glunz1, Yan Zou1
1Bristol-Myers Squibb Research & Development, Princeton, NJ 08543, United States.
Abstract:
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.
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