Dibasic inhibitors of human mast cell tryptase. Part 1: synthesis and optimization of a novel class of inhibitors.
The synthesis and optimization of a novel class of reversible and active-site directed dibasic inhibitors of human mast cell tryptase are described. The compounds were shown to be both remarkably potent and selective for tryptase with Ki values for optimized inhibitors in the picomolar range.
Rice
K D
KD
Department of Medicinal Chemistry, Axys Pharmaceuticals, Inc., South San Francisco, CA 94080, USA.
Gangloff
A R
AR
Kuo
E Y
EY
Dener
J M
JM
Wang
V R
VR
Lum
R
R
Newcomb
W S
WS
Havel
C
C
Putnam
D
D
Cregar
L
L
Wong
M
M
Warne
R L
RL
D043925:Angiogenesis Inducing Agents / Q000037:antagonists & inhibitors; D001665:Binding Sites; D001667:Binding, Competitive; D003959:Diamines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D006801:Humans; D009757:Nylons / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D012697:Serine Endopeptidases / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D053802:Tryptases; D014992:Xylenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
D043925:Angiogenesis Inducing Agents; D003959:Diamines; D009757:Nylons; D015842:Serine Proteinase Inhibitors; D014992:Xylenes; C066883:1,3-xylenediamine; D012697:Serine Endopeptidases; D053802:Tryptases