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

Richter, Jeremy M.; Cheney, Daniel L.; Bates, J. Alex; Wei, Anzhi; Luettgen, Joseph M.; Rendina, Alan R.; Harper, Timothy M.; Narayanan, Rangaraj; Wong, Pancras C.; Seiffert, Dietmar; Wexler, Ruth R.; Priestley, E. Scott

doi:10.1021/acsmedchemlett.6b00375

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

Journal Article · Sun Nov 06 23:00:00 EST 2016 · ACS Medicinal Chemistry Letters

DOI:https://doi.org/10.1021/acsmedchemlett.6b00375· OSTI ID:1347772

Richter, Jeremy M. ^[1]; Cheney, Daniel L. ^[1]; Bates, J. Alex ^[1]; Wei, Anzhi ^[1]; Luettgen, Joseph M. ^[1]; Rendina, Alan R. ^[1]; Harper, Timothy M. ^[1]; Narayanan, Rangaraj ^[1]; Wong, Pancras C. ^[1]; Seiffert, Dietmar ^[1]; Wexler, Ruth R. ^[1]; Priestley, E. Scott ^[1]

Bristol-Myers Squibb, Hopewell, NJ (United States)

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 Ki was improved to subnanomolar levels with good clotting activity, metabolic stability, and permeability.

View Accepted Manuscript (DOE)

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (US)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)

OSTI ID:: 1347772

Journal Information:: ACS Medicinal Chemistry Letters, Journal Name: ACS Medicinal Chemistry Letters Journal Issue: 1 Vol. 8; ISSN 1948-5875

Publisher:: American Chemical Society (ACS)Copyright Statement

Country of Publication:: United States

Language:: ENGLISH

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Cited By (2)

Reactivity and Synthetic Applications of Multicomponent Petasis Reactions Wu, Peng; Givskov, Michael; Nielsen, Thomas E. Chemical Reviews, Vol. 119, Issue 20 https://doi.org/10.1021/acs.chemrev.9b00214	journal	August 2019
BindingDB Entry 50048136: Design and Synthesis of Novel Meta-Linked Phenylglycine Macrocyclic FVIIa Inhibitors. No authors listed BindingDB https://doi.org/10.7270/q20p120q	dataset	January 2018

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60 APPLIED LIFE SCIENCES
FVIIa
anticoagulant
antithrombotic
factor VIIa
macrocycle
thrombosis

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

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References (30)

Cited By (2)

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