The SAR of 4-substituted (6,6-bicyclic) piperidine cathepsin S inhibitors.
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.
Grice
Cheryl A
CA
Johnson and Johnson Pharmaceutical Research and Development, L.L.C., 3210 Merryfield Row, San Diego, CA 92121, USA. cgrice@prdus.jnj.com
Tays
Kevin
K
Khatuya
Haripada
H
Gustin
Darin J
DJ
Butler
Christopher R
CR
Wei
Jianmei
J
Sehon
Clark A
CA
Sun
Siquan
S
Gu
Yin
Y
Jiang
Wen
W
Thurmond
Robin L
RL
Karlsson
Lars
L
Edwards
James P
JP
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
D001643:Bridged Bicyclo Compounds; D004791:Enzyme Inhibitors; D010880:Piperidines; C032727:piperidine; D002403:Cathepsins; C028217:cathepsin S