title: The SAR of 4-substituted (6,6-bicyclic) piperidine cathepsin S inhibitors.
abstract: A series of competitive, reversible cathepsin S (CatS) inhibitors was investigated. An earlier disclosure detailed the discovery of the 4-(2-keto-1-benzimidazolinyl)-piperidin-1-yl moiety as an effective replacement for the 4-arylpiperazin-1-yl group found in our screening hit. Continued investigation into replacements for the 4-aryl piperazine resulted in the identification of potentially useful CatS inhibitors with enzymatic and cellular activity similar to that of JNJ 10329670 as disclosed in a previous publication.
authors.affiliation: Johnson and Johnson Pharmaceutical Research and Development, L.L.C., 3210 Merryfield Row, San Diego, CA 92121, USA. cgrice@prdus.jnj.com
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Grice
authors.forename: Kevin
authors.initials: K
authors.lastname: Tays
authors.forename: Haripada
authors.initials: H
authors.lastname: Khatuya
authors.forename: Darin J
authors.initials: DJ
authors.lastname: Gustin
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Butler
authors.forename: Jianmei
authors.initials: J
authors.lastname: Wei
authors.forename: Clark A
authors.initials: CA
authors.lastname: Sehon
authors.forename: Siquan
authors.initials: S
authors.lastname: Sun
authors.forename: Yin
authors.initials: Y
authors.lastname: Gu
authors.forename: Wen
authors.initials: W
authors.lastname: Jiang
authors.forename: Robin L
authors.initials: RL
authors.lastname: Thurmond
authors.forename: Lars
authors.initials: L
authors.lastname: Karlsson
authors.forename: James P
authors.initials: JP
authors.lastname: Edwards
mesh_terms: D000818:Animals; D001665:Binding Sites; D001643:Bridged Bicyclo Compounds / Q000737:chemistry* / Q000494:pharmacology; D002403:Cathepsins / Q000037:antagonists & inhibitors*; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D051379:Mice; D010880:Piperidines / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D001643:Bridged Bicyclo Compounds; D004791:Enzyme Inhibitors; D010880:Piperidines; C032727:piperidine; D002403:Cathepsins; C028217:cathepsin S