title: Identification of a novel class of succinyl-nitrile-based Cathepsin S inhibitors.
abstract: The synthesis and in vitro activities of a series of succinyl-nitrile-based inhibitors of Cathepsin S are described. Several members of this class show nanomolar inhibition of the target enzyme as well as cellular potency. The inhibitors displaying the greatest potency contain N-alkyl substituted piperidine and pyrrolidine rings spiro-fused to the alpha-carbon of the P1 residue.
authors: Department of Medicinal Chemistry, Boehringer Ingelheim Pharmaceuticals Inc., 900 Ridgebury Road, PO Box 368, Ridgefield, CT 06877-0368, USA. ybekkali@rdg.boehringer-ingelheim.com
authors: Younes
authors: Y
authors: Bekkali
authors: David S
authors: DS
authors: Thomson
authors: Raj
authors: R
authors: Betageri
authors: Michel J
authors: MJ
authors: Emmanuel
authors: Ming-Hong
authors: MH
authors: Hao
authors: Eugene
authors: E
authors: Hickey
authors: Weimin
authors: W
authors: Liu
authors: Usha
authors: U
authors: Patel
authors: Yancey D
authors: YD
authors: Ward
authors: Erick R R
authors: ER
authors: Young
authors: Richard
authors: R
authors: Nelson
authors: Alison
authors: A
authors: Kukulka
authors: Maryanne L
authors: ML
authors: Brown
authors: Kathy
authors: K
authors: Crane
authors: Della
authors: D
authors: White
authors: Dorothy M
authors: DM
authors: Freeman
authors: Mark E
authors: ME
authors: Labadia
authors: Jessi
authors: J
authors: Wildeson
authors: Denice M
authors: DM
authors: Spero
mesh_terms: D020134:Catalytic Domain; D002403:Cathepsins / Q000037:antagonists & inhibitors*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004151:Dipeptides / Q000737:chemistry; D015195:Drug Design; D006801:Humans; D008956:Models, Chemical; D008968:Molecular Conformation; D009570:Nitriles / Q000737:chemistry* / Q000145:classification; D010455:Peptides / Q000737:chemistry; D010880:Piperidines / Q000737:chemistry; D011759:Pyrrolidines / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D004151:Dipeptides; D009570:Nitriles; D010455:Peptides; D010880:Piperidines; D011759:Pyrrolidines; C032727:piperidine; D002403:Cathepsins; C028217:cathepsin S; C032519:pyrrolidine