1.
Bioorg Med Chem Lett
; 15(24): 5434-8, 2005 Dec 15.
Article
in English
| MEDLINE
| ID: mdl-16216507
ABSTRACT
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.
Subject(s)
Biomimetics , Bridged Bicyclo Compounds, Heterocyclic/pharmacology , Caspase Inhibitors , Enzyme Inhibitors/pharmacology , Bridged Bicyclo Compounds, Heterocyclic/chemical synthesis , Enzyme Inhibitors/chemical synthesis , Humans , Indicators and Reagents , Models, Molecular , Molecular Conformation
2.
Bioorg Med Chem Lett
; 15(19): 4291-4, 2005 Oct 01.
Article
in English
| MEDLINE
| ID: mdl-16046125
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.