title: 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/FVIIaKiwas improved to subnanomolar levels with good clotting activity, metabolic stability, and permeability.
authors.affiliation: Research & Development, Bristol-Myers Squibb , Hopewell, New Jersey 08534, United States.
authors.forename: Jeremy M
authors.initials: JM
authors.lastname: Richter
authors.affiliation: Research & Development, Bristol-Myers Squibb , Hopewell, New Jersey 08534, United States.
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Cheney
authors.affiliation: Research & Development, Bristol-Myers Squibb , Hopewell, New Jersey 08534, United States.
authors.forename: J Alex
authors.initials: JA
authors.lastname: Bates
authors.affiliation: Research & Development, Bristol-Myers Squibb , Hopewell, New Jersey 08534, United States.
authors.forename: Anzhi
authors.initials: A
authors.lastname: Wei
authors.affiliation: Research & Development, Bristol-Myers Squibb , Hopewell, New Jersey 08534, United States.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Luettgen
authors.affiliation: Research & Development, Bristol-Myers Squibb , Hopewell, New Jersey 08534, United States.
authors.forename: Alan R
authors.initials: AR
authors.lastname: Rendina
authors.affiliation: Research & Development, Bristol-Myers Squibb , Hopewell, New Jersey 08534, United States.
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Harper
authors.affiliation: Research & Development, Bristol-Myers Squibb , Hopewell, New Jersey 08534, United States.
authors.forename: Rangaraj
authors.initials: R
authors.lastname: Narayanan
authors.affiliation: Research & Development, Bristol-Myers Squibb , Hopewell, New Jersey 08534, United States.
authors.forename: Pancras C
authors.initials: PC
authors.lastname: Wong
authors.affiliation: Research & Development, Bristol-Myers Squibb , Hopewell, New Jersey 08534, United States.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Seiffert
authors.affiliation: Research & Development, Bristol-Myers Squibb , Hopewell, New Jersey 08534, United States.
authors.forename: Ruth R
authors.initials: RR
authors.lastname: Wexler
authors.affiliation: Research & Development, Bristol-Myers Squibb , Hopewell, New Jersey 08534, United States.
authors.forename: E Scott
authors.initials: ES
authors.lastname: Priestley
keywords: FVIIa; anticoagulant; antithrombotic; factor VIIa; macrocycle; thrombosis