title: Arylaminoethyl amides as novel non-covalent cathepsin K inhibitors.
abstract: A series of N(alpha)-benzyloxycarbonyl- and N(alpha)-acyl-L-leucine(2-phenylaminoethyl)amide derivatives were prepared and evaluated for their inhibitory activity against rabbit and human cysteine proteases cathepsins K, L, and S. These data indicate that N(alpha)-acyl-alpha-amino acid-(arylaminoethyl)amides represent a new class of selective non-covalent inhibitors of cathepsin K. Compounds 4b, 4e, and 4g exhibit high potency toward rabbit and human cathepsin K (IC(50) < 0.006 microM) and are characterized by an excellent selectivity profile vs human cathepsins L and S.
authors.forename: Eva
authors.initials: E
authors.lastname: Altmann
authors.forename: Johanne
authors.initials: J
authors.lastname: Renaud
authors.forename: Jonathan
authors.initials: J
authors.lastname: Green
authors.forename: David
authors.initials: D
authors.lastname: Farley
authors.forename: Brian
authors.initials: B
authors.lastname: Cutting
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Jahnke
mesh_terms: D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry; D000818:Animals; D056657:Cathepsin K; D002403:Cathepsins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D015853:Cysteine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D005453:Fluorescence; D006801:Humans; D007700:Kinetics; D011817:Rabbits; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D015853:Cysteine Proteinase Inhibitors; D011994:Recombinant Proteins; D002403:Cathepsins; C534130:CTSK protein, human; D056657:Cathepsin K