2. Academic Validation
  3. Nicotinyl aspartyl ketones as inhibitors of caspase-3

Nicotinyl aspartyl ketones as inhibitors of caspase-3

  • Bioorg Med Chem Lett. 2003 Jul 7;13(13):2137-40. doi: 10.1016/s0960-894x(03)00390-1.
Elise Isabel 1,  W Cameron Black,  Christopher I Bayly,  Erich L Grimm,  Marc K Janes,  Daniel J McKay,  Donald W Nicholson,  Dita M Rasper,  Johanne Renaud,  Sophie Roy,  John Tam,  Nancy A Thornberry,  John P Vaillancourt,  Steven Xanthoudakis,  Robert Zamboni
Affiliations

Affiliation

  • 1 Merck Frosst Centre for Therapeutic Research, Merck Frosst Canada & Co., Pointe-Claire-Dorval, H9R 4P8, Quebec, Canada. [email protected]
PMID: 12798321 DOI: 10.1016/s0960-894x(03)00390-1
Abstract

Caspase-3 is a cysteinyl protease that mediates apoptotic cell death. Its inhibition may have an important impact in the treatment of several degenerative diseases. Since P(1) aspartic acid is a required element of recognition for this enzyme, a library of capped aspartyl aldehydes was synthesized using solid-phase chemistry. The 5-bromonicotinamide derivative of the aspartic acid aldehyde was identified to be an inhibitor of Caspase-3. Substitution at the 5-position of the pyridine ring and conversion of the aldehyde to ketones led to a series of potent inhibitors of Caspase-3.

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