National Center for
1WU1: Factor Xa In Complex With The Inhibitor 4-[(5-Chloroindol-2-Yl) Sulfonyl]-2-(2-Methylpropyl)-1-[[5-(Pyridin-4-Yl) Pyrimidin-2- Yl]carbonyl]piperazine
Design, synthesis, and biological activity of non-basic compounds as factor Xa inhibitors: SAR study of S1 and aryl binding sites
Bioorg. Med. Chem. (2005) 13 p.3927-3954» All references (5)
Compound 7 was identified as the active metabolite of 6 by HPLC and mass spectral analysis. Modification of lead compound 7 by transformation of its N-oxide 6-6 biaryl ring system and fused aromatics produced a series of non-basic fXa inhibitors with excellent potency in anti-fXa and anticoagulant assays. The optimized compounds 73b and 75b showed sub to one digit micromolar anticoagulant activity (PTCT2). Particularly, anti-fXa activity was detected in plasma of rats orally administered with 1mg/kg of compound 75b.