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ABSTRACT: Plasma kallikrein is a serine protease that is involved in pathways of inflammation, complement fixation, coagulation, and fibrinolysis. Herein, we describe the SAR and structural binding modes of a series of inhibitors of plasma kallikrein as well as the pharmacokinetics of a lead analog 11 in rat.
Bioorganic & Medicinal Chemistry Letters 05/2006; 16(7):2034-6. · 2.55 Impact Factor
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William D Shrader,
Aleksandr Kolesnikov, Jana Burgess-Henry,
Roopa Rai,
John Hendrix,
Huiyong Hu,
Steve Torkelson,
Tony Ton,
Wendy B Young,
Bradley A Katz,
Christine Yu,
Jie Tang,
Ronnel Cabuslay,
Ellen Sanford,
James W Janc,
Paul A Sprengeler
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ABSTRACT: Within the trypsin family of coagulation proteases, obtaining highly selective inhibitors of factor VIIa has been challenging. We report a series of factor VIIa (fVIIa) inhibitors based on the 5-amidino-2-(2-hydroxy-biphenyl-3-yl)-benzimidazole (1) scaffold with potency for fVIIa and high selectivity against factors IIa, Xa, and trypsin. With this scaffold class, we propose that a unique hydrogen bond interaction between a hydroxyl on the distal ring of the biaryl system and the backbone carbonyl of fVIIa lysine-192 provides a basis for enhanced selectivity and potency for fVIIa.
Bioorganic & Medicinal Chemistry Letters 04/2006; 16(6):1596-600. · 2.55 Impact Factor
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Roopa Rai,
Aleksandr Kolesnikov,
Yong Li,
Wendy B Young,
Ellen Leahy,
Paul A Sprengeler,
Erik Verner,
William D Shrader, Jana Burgess-Henry,
Joan C Sangalang,
Darin Allen,
Xi Chen,
Bradley A Katz,
Christine Luong,
Kyle Elrod,
Lynne Cregar
Bioorganic & Medicinal Chemistry Letters 08/2001; 11(14):1797-1800. · 2.55 Impact Factor
