Discovery of novel conformationally restricted diazocan peptidomimetics as inhibitors of interleukin-1beta synthesis.
A novel diazocan containing dipeptide mimetic was synthesized via reductive N-N bond cleavage of a pyrazolidino-pyrazolidine using Raney-Ni and evaluated as an ICE inhibitor. This versatile 8-membered ring containing scaffold possesses an N-5 ring nitrogen that was used to explore structure-activity relationships in a cell-based assay measuring inhibition of interleukin-1beta.
Oppong
Kofi A
KA
Procter & Gamble Pharmaceuticals, Inc., 8700 Mason-Montgomery Road, Mason, OH 45040, USA. Oppong.ka@pg.com
Ellis
Christopher D
CD
Laufersweiler
Michael C
MC
O'Neil
Steven V
SV
Wang
Yili
Y
Soper
David L
DL
Baize
Mark W
MW
Wos
John A
JA
De
Biswanath
B
Bosch
Gregory K
GK
Fancher
Amy N
AN
Lu
Wei
W
Suchanek
Maureen K
MK
Wang
Richard L
RL
Demuth
Thomas P
TP
D061945:Caspase Inhibitors; D004151:Dipeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D020128:Inhibitory Concentration 50; D007375:Interleukin-1 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D008968:Molecular Conformation; D018716:Molecular Mimicry; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011720:Pyrazoles / Q000737:chemistry; D013329:Structure-Activity Relationship
D061945:Caspase Inhibitors; D004151:Dipeptides; D007375:Interleukin-1; D010456:Peptides, Cyclic; D011720:Pyrazoles; C506218:diazocan