Novel pyrazinone inhibitors of mast cell tryptase: synthesis and SAR evaluation

Corey Hopkins; Kent Neuenschwander; Anthony Scotese; Sharon Jackson; Thaddeus Nieduzak; Henry Pauls; Guyan Liang; Keith Sides; Dona Cramer; Jennifer Cairns; Sebastien Maignan; Magali Mathieu

doi:10.1016/j.bmcl.2004.07.051

Novel pyrazinone inhibitors of mast cell tryptase: synthesis and SAR evaluation

Bioorg Med Chem Lett. 2004 Oct 4;14(19):4819-23. doi: 10.1016/j.bmcl.2004.07.051.

Authors

Corey Hopkins¹, Kent Neuenschwander, Anthony Scotese, Sharon Jackson, Thaddeus Nieduzak, Henry Pauls, Guyan Liang, Keith Sides, Dona Cramer, Jennifer Cairns, Sebastien Maignan, Magali Mathieu

Affiliation

¹ Department of Medicinal Chemistry, Drug Innovation and Approval, Aventis Pharmaceuticals, Route 202-206, Bridgewater, NJ 08807, USA. [email protected]

PMID: 15341931
DOI: 10.1016/j.bmcl.2004.07.051

Abstract

In this manuscript, the synthesis and SAR evaluation of a novel pyrazinone class of tryptase inhibitors is described. Chemical optimization of the P1 and P4 groups led to the identification of 7p (K(i)=93 nM) as a potent inhibitor of mast cell tryptase.

MeSH terms

Pyrazines / chemical synthesis*
Pyrazines / pharmacology
Serine Endopeptidases / chemistry
Serine Endopeptidases / drug effects*
Serine Proteinase Inhibitors / chemical synthesis*
Serine Proteinase Inhibitors / pharmacology
Structure-Activity Relationship
Tryptases

Substances

Pyrazines
Serine Proteinase Inhibitors
Serine Endopeptidases
Tryptases