title: Discovery of novel conformationally restricted diazocan peptidomimetics as inhibitors of interleukin-1beta synthesis.
abstract: 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.
authors.affiliation: Procter & Gamble Pharmaceuticals, Inc., 8700 Mason-Montgomery Road, Mason, OH 45040, USA. Oppong.ka@pg.com
authors.forename: Kofi A
authors.initials: KA
authors.lastname: Oppong
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Ellis
authors.forename: Michael C
authors.initials: MC
authors.lastname: Laufersweiler
authors.forename: Steven V
authors.initials: SV
authors.lastname: O'Neil
authors.forename: Yili
authors.initials: Y
authors.lastname: Wang
authors.forename: David L
authors.initials: DL
authors.lastname: Soper
authors.forename: Mark W
authors.initials: MW
authors.lastname: Baize
authors.forename: John A
authors.initials: JA
authors.lastname: Wos
authors.forename: Biswanath
authors.initials: B
authors.lastname: De
authors.forename: Gregory K
authors.initials: GK
authors.lastname: Bosch
authors.forename: Amy N
authors.initials: AN
authors.lastname: Fancher
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
authors.forename: Maureen K
authors.initials: MK
authors.lastname: Suchanek
authors.forename: Richard L
authors.initials: RL
authors.lastname: Wang
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Demuth
mesh_terms: 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
chemical_list: D061945:Caspase Inhibitors; D004151:Dipeptides; D007375:Interleukin-1; D010456:Peptides, Cyclic; D011720:Pyrazoles; C506218:diazocan