title: Synthesis and biological evaluation of novel piperidine carboxamide derived calpain inhibitors.
abstract: Calpain inhibitors which are derived from piperidine carboxamides in the P2 region were prepared and evaluated for mu-calpain inhibition. In particular, the keto amides 11f and 11j have Ki of 30 and 9 nM and display a more than 100-fold selectivity over the closely related cysteine protease cathepsin B. Furthermore, these compounds inhibit NMDA induced convulsions in mice indicating that calpain inhibition in brain results in some anticonvulsive properties.
authors.affiliation: Department of Discovery Research, KNOLL AG, Ludwigshafen, Germany. wilfried.lubisch@knoll-ag.de
authors.forename: W
authors.initials: W
authors.lastname: Lubisch
authors.forename: H P
authors.initials: HP
authors.lastname: Hofmann
authors.forename: H J
authors.initials: HJ
authors.lastname: Treiber
authors.forename: A
authors.initials: A
authors.lastname: Möller
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002154:Calpain / Q000037:antagonists & inhibitors*; D002401:Cathepsin B / Q000037:antagonists & inhibitors; D015853:Cysteine Proteinase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D004151:Dipeptides / Q000737:chemistry / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D051379:Mice; D015394:Molecular Structure; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship
chemical_list: C419201:1-(2-benzothienylcarbonyl)piperidin-4-ylcarbonyl-phenylalaninamide; C419200:1-(2-naphthylcarbonyl)piperidin-4-ylcarbonyl-phenylalaninamide; D000927:Anticonvulsants; D015853:Cysteine Proteinase Inhibitors; D004151:Dipeptides; D009842:Oligopeptides; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D002154:Calpain; D002401:Cathepsin B; C058076:calpain inhibitor III