Synthesis and evaluation of novel 8,6-fused bicyclic peptidomimetic compounds as interleukin-1beta converting enzyme inhibitors.
Two novel 8,6-fused bicyclic peptidomimetic ring systems were synthesized utilizing olefin metathesis as the key reaction for the formation of the eight-membered ring. Both peptidomimetic scaffolds were further elaborated into potent ICE inhibitors, with numerous compounds exhibiting caspase-1 IC(50)s less than 10nM.
O'Neil
Steven V
SV
Procter & Gamble Pharmaceuticals, Inc., 8700 Mason-Montgomery Road, Mason, OH 45040, USA. oneil.sv@pg.com
Wang
Yili
Y
Laufersweiler
Michael C
MC
Oppong
Kofi A
KA
Soper
David L
DL
Wos
John A
JA
Ellis
Christopher D
CD
Baize
Mark W
MW
Bosch
Gregory K
GK
Fancher
Amy N
AN
Lu
Wei
W
Suchanek
Maureen K
MK
Wang
Richard L
RL
De
Biswanath
B
Demuth
Thomas P
TP
D032701:Biomimetics; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis / Q000494:pharmacology*; D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D007202:Indicators and Reagents; D008958:Models, Molecular; D008968:Molecular Conformation
D019086:Bridged Bicyclo Compounds, Heterocyclic; D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D007202:Indicators and Reagents