The de novo design and synthesis of cyclic urea inhibitors of factor Xa: optimization of the S4 ligand

R A Galemmo Jr; B L Wells; K A Rossi; R S Alexander; C Dominguez; T P Maduskuie; P F Stouten; M R Wright; B J Aungst; P C Wong; R M Knabb; R R Wexler

doi:10.1016/s0960-894x(99)00688-5

The de novo design and synthesis of cyclic urea inhibitors of factor Xa: optimization of the S4 ligand

Bioorg Med Chem Lett. 2000 Feb 7;10(3):301-4. doi: 10.1016/s0960-894x(99)00688-5.

Authors

R A Galemmo Jr¹, B L Wells, K A Rossi, R S Alexander, C Dominguez, T P Maduskuie, P F Stouten, M R Wright, B J Aungst, P C Wong, R M Knabb, R R Wexler

Affiliation

¹ DuPont Pharmaceuticals Company, Wilmington, DE 19880-0500, USA. robert.a.galemmo@dupontpharma.com

PMID: 10698459
DOI: 10.1016/s0960-894x(99)00688-5

Abstract

In this report refinements to the S4 ligand group leads to compound 19, an inhibitor of fXa with good potency in vitro and an improved pharmacokinetic profile in rabbit. The X-ray crystallographic study of a representative analogue confirms our binding model for this series.

MeSH terms

Animals
Crystallography, X-Ray
Factor Xa Inhibitors*
Ligands
Models, Molecular
Rabbits
Serine Proteinase Inhibitors / chemical synthesis*
Serine Proteinase Inhibitors / pharmacokinetics
Serine Proteinase Inhibitors / pharmacology
Urea / chemical synthesis*
Urea / pharmacokinetics
Urea / pharmacology

Substances

Factor Xa Inhibitors
Ligands
Serine Proteinase Inhibitors
Urea