Structure based design of 4-(3-aminomethylphenyl) piperidinyl-1-amides: novel, potent, selective, and orally bioavailable inhibitors of βII tryptase

…, S Maignan, JP Guilloteau, A Dupuy, J Davidson…

Index: Levell, Julian; Astles, Peter; Eastwood, Paul; Cairns, Jennifer; Houille, Olivier; Aldous, Suzanne; Merriman, Gregory; Whiteley, Brian; Pribish, James; Czekaj, Mark; Liang, Guyan; Maignan, Sebastien; Guilloteau, Jean-Pierre; Dupuy, Alain; Davidson, Jane; Harrison, Trevor; Morley, Andrew; Watson, Simon; Fenton, Garry; McCarthy, Clive; Romano, Joseph; Mathew, Rose; Engers, Darren; Gardyan, Michael; Sides, Keith; Kwong, Jennifer; Tsay, Joseph; Rebello, Sam; Shen, Liduo; Wang, Jie; Luo, Yongyi; Giardino, Odessa; Lim, Heng-Keang; Smith, Keith; Pauls, Henry Bioorganic and Medicinal Chemistry, 2005 , vol. 13, # 8 p. 2859 - 2872

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Citation Number: 22

Abstract

Tryptase is a serine protease found almost exclusively in mast cells. It has trypsin-like specificity, favoring cleavage of substrates with an arginine (or lysine) at the P1 position, and has optimal catalytic activity at neutral pH. Current evidence suggests tryptase β is the ...