Design of novel, potent, and selective human beta-tryptase inhibitors based on alpha-keto-[1,2,4]-oxadiazoles.
A series of novel alpha-keto-[1,2,4]-oxadiazoles has been synthesized as human tryptase inhibitors for evaluation as a new class of anti-asthmatic agent. The inhibitor design is focused on using a prime-side hydrophobic pocket and the S2 pocket of beta-tryptase to achieve inhibition potency and selectivity over other serine proteases.
Lee
Chang-Sun
CS
Department of Chemistry, Celera, 180 Kimball Way, South San Francisco, CA 94080, USA. csleesammy@gmail.com
Liu
Weili
W
Sprengeler
Paul A
PA
Somoza
John R
JR
Janc
James W
JW
Sperandio
David
D
Spencer
Jeffrey R
JR
Green
Michael J
MJ
McGrath
Mary E
ME
D018360:Crystallography, X-Ray; D006801:Humans; D007700:Kinetics; D010080:Oxazoles / Q000737:chemistry / Q000494:pharmacology*; D012697:Serine Endopeptidases / Q000187:drug effects*; D053802:Tryptases
D010080:Oxazoles; D012697:Serine Endopeptidases; D053802:Tryptases