Discovery of phenyl alanine derived ketoamides carrying benzoyl residues as novel calpain inhibitors

W Lubisch; A Möller

doi:10.1016/s0960-894x(02)00176-2

Discovery of phenyl alanine derived ketoamides carrying benzoyl residues as novel calpain inhibitors

Bioorg Med Chem Lett. 2002 May 20;12(10):1335-8. doi: 10.1016/s0960-894x(02)00176-2.

Authors

W Lubisch¹, A Möller

Affiliation

¹ Department of CNS Discovery Research, Abbott GmbH&Co. KG, PO Box 210805, 67008, Ludwigshafen, Germany. [email protected]

PMID: 11992771
DOI: 10.1016/s0960-894x(02)00176-2

Abstract

Novel calpain inhibitors derived from phenyl alanine aldehydes or ketoamides carrying a benzoyl residue were prepared and evaluated for their biological potency. A brief structure-activity relationship elucidated the importance of ortho-substitutents in the benzoyl moiety. The most potent derivative, the ketoamide 19c, exhibited a K(i) of 6nM and represents a novel class of reversible, highly potent and non-peptidic calpain inhibitors.

MeSH terms

Amides / chemical synthesis
Amides / pharmacology
Blood Platelets / enzymology
Calpain / antagonists & inhibitors*
Calpain / blood
Cysteine Proteinase Inhibitors / chemical synthesis*
Cysteine Proteinase Inhibitors / pharmacology
Drug Design
Humans
Keto Acids / chemical synthesis*
Keto Acids / pharmacology
Models, Molecular
Molecular Conformation
Phenylalanine*
Structure-Activity Relationship

Substances

Amides
Cysteine Proteinase Inhibitors
Keto Acids
Phenylalanine
Calpain