Synthesis and evaluation of novel 8,6-fused bicyclic peptidomimetic compounds as interleukin-1b converting enzyme inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 15, Issue 24, 2005, Pages 5434-5438

  O'Neil, Steven V ^a   Wang, Yili ^a   Laufersweiler, Michael C ^a   Oppong, Kofi A ^a   Soper, David L ^a   Wos, John A ^a   Ellis, Christopher D ^a   Baize, Mark W ^a   Bosch, Gregory K ^a   Fancher, Amy N ^a   Lu, Wei ^a   Suchanek, Maureen K ^a   Wang, Richard L ^a   De, Biswanath ^a   Demuth Jr , Thomas P ^a  

^a PROCTER AND GAMBLE PHARMACEUTICALS   (United States)

Author keywords

Caspase; Interleukin 1 converting enzyme inhibitors; Olefin metathesis; Peptidomimetic

Indexed keywords

ALKENE; BICYCLO COMPOUND; INTERLEUKIN 1BETA CONVERTING ENZYME; INTERLEUKIN 1BETA CONVERTING ENZYME INHIBITOR;

ALLYLATION; ARTICLE; CHEMICAL REACTION; COMPARATIVE STUDY; CONFORMATIONAL TRANSITION; CONTROLLED STUDY; DRUG POTENCY; DRUG SCREENING; DRUG SYNTHESIS; HUMAN; HUMAN CELL; IC 50; OZONOLYSIS;

BICYCLO COMPOUNDS, HETEROCYCLIC; BIOMIMETICS; CASPASE 1; ENZYME INHIBITORS; HUMANS; INDICATORS AND REAGENTS; MODELS, MOLECULAR; MOLECULAR CONFORMATION;

EID: 27644585300     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2005.08.109     Document Type: Article

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23. o is the initial velocity in the absence of inhibitor.
24. 6/ml in RPMI 1640 medium from Gibco-BRL) was plated in 96-well plates, incubated with or without compounds (administered as solutions in DMSO, such that test concentrations ranged from 1 nM to 10 μM) for 15 min, and then stimulated with LPS (1 μg/ml) for a total of 4 h. Cells were centrifuged and the conditioned media were collected to quantify the release of IL-1β by an ELISA measurement according to the manufacturer's instructions (R&D Systems, catalog No. DLB50) or stored at -20°C for future use.