Novel pyrazinone inhibitors of mast cell tryptase: synthesis and SAR evaluation.
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.
Hopkins
Corey
C
Department of Medicinal Chemistry, Drug Innovation and Approval, Aventis Pharmaceuticals, Route 202-206, Bridgewater, NJ 08807, USA. corey.hopkins@aventis.com
Neuenschwander
Kent
K
Scotese
Anthony
A
Jackson
Sharon
S
Nieduzak
Thaddeus
T
Pauls
Henry
H
Liang
Guyan
G
Sides
Keith
K
Cramer
Dona
D
Cairns
Jennifer
J
Maignan
Sebastien
S
Mathieu
Magali
M
D011719:Pyrazines / Q000138:chemical synthesis* / Q000494:pharmacology; D012697:Serine Endopeptidases / Q000737:chemistry / Q000187:drug effects*; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D053802:Tryptases
D011719:Pyrazines; D015842:Serine Proteinase Inhibitors; D012697:Serine Endopeptidases; D053802:Tryptases