Amido-(propyl and allyl)-hydroxybenzamidines: development of achiral inhibitors of factor Xa

Y Gong; H W Pauls; A P Spada; M Czekaj; G Liang; V Chu; D J Colussi; K D Brown; J Gao

doi:10.1016/s0960-894x(99)00673-3

Amido-(propyl and allyl)-hydroxybenzamidines: development of achiral inhibitors of factor Xa

Bioorg Med Chem Lett. 2000 Feb 7;10(3):217-21. doi: 10.1016/s0960-894x(99)00673-3.

Authors

Y Gong¹, H W Pauls, A P Spada, M Czekaj, G Liang, V Chu, D J Colussi, K D Brown, J Gao

Affiliation

¹ Department of Medicinal Chemistry, Rhone-Poulenc Rorer, Collegeville, PA 19426-0107, USA.

PMID: 10698439
DOI: 10.1016/s0960-894x(99)00673-3

Abstract

The design, synthesis and SAR of amido-(propyl and allyl)-hydroxybenzamidine coagulation factor Xa inhibitors is described. These achiral inhibitors are selective for fXa vis a vis structurally related serine proteases and are readily prepared in 6-7 linear steps. The most potent member 9j (fXa Ki = 0.75 nM) is selective (>1000-fold) and an effective anticoagulant in mammalian plasma.

MeSH terms

Animals
Benzamidines / chemical synthesis*
Benzamidines / chemistry
Benzamidines / pharmacology
Factor Xa Inhibitors*
Models, Molecular
Molecular Structure
Serine Proteinase Inhibitors / chemical synthesis*
Serine Proteinase Inhibitors / chemistry
Serine Proteinase Inhibitors / pharmacology

Substances

Benzamidines
Factor Xa Inhibitors
Serine Proteinase Inhibitors