title: 6-Phenyl-1H-imidazo[4,5-c]pyridine-4-carbonitrile as cathepsin S inhibitors.
abstract: 6-Phenyl-1H-imidazo[4,5-c]pyridine-4-carbonitrile analogues were identified as potent and selective cathepsin S inhibitor against both purified enzyme and in human JY cell based cellular assays. This core has a very stable thio-trapping nitrile war-head in comparison with the well reported pyrimidine-2-carbonitrile cysteine cathepsin inhibitors. Compound 47 is also very potent in in vivo mouse spleenic Lip10 accumulation assays.
authors.affiliation: Merck Research Laboratories, Newhouse, Lanarkshire ML1 5SH, UK. jiaqiang.cai@merck.com
authors.forename: Jiaqiang
authors.initials: J
authors.lastname: Cai
authors.forename: Mark
authors.initials: M
authors.lastname: Baugh
authors.forename: Darcey
authors.initials: D
authors.lastname: Black
authors.forename: Clive
authors.initials: C
authors.lastname: Long
authors.forename: D
authors.initials: D
authors.lastname: Jonathan Bennett
authors.forename: Maureen
authors.initials: M
authors.lastname: Dempster
authors.forename: Xavier
authors.initials: X
authors.lastname: Fradera
authors.forename: Jonathan
authors.initials: J
authors.lastname: Gillespie
authors.forename: Fiona
authors.initials: F
authors.lastname: Andrews
authors.forename: Sylviane
authors.initials: S
authors.lastname: Boucharens
authors.forename: John
authors.initials: J
authors.lastname: Bruin
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Cameron
authors.forename: Iain
authors.initials: I
authors.lastname: Cumming
authors.forename: William
authors.initials: W
authors.lastname: Hamilton
authors.forename: Philip S
authors.initials: PS
authors.lastname: Jones
authors.forename: Allard
authors.initials: A
authors.lastname: Kaptein
authors.forename: Emma
authors.initials: E
authors.lastname: Kinghorn
authors.forename: Maurice
authors.initials: M
authors.lastname: Maidment
authors.forename: Iain
authors.initials: I
authors.lastname: Martin
authors.forename: Ann
authors.initials: A
authors.lastname: Mitchell
authors.forename: Zoran
authors.initials: Z
authors.lastname: Rankovic
authors.forename: John
authors.initials: J
authors.lastname: Robinson
authors.forename: Paul
authors.initials: P
authors.lastname: Scullion
authors.forename: Joost C M
authors.initials: JC
authors.lastname: Uitdehaag
authors.forename: Paul
authors.initials: P
authors.lastname: Vink
authors.forename: Paul
authors.initials: P
authors.lastname: Westwood
authors.forename: Mario
authors.initials: M
authors.lastname: van Zeeland
authors.forename: Leon
authors.initials: L
authors.lastname: van Berkom
authors.forename: Martijn
authors.initials: M
authors.lastname: Bastiani
authors.forename: Tommi
authors.initials: T
authors.lastname: Meulemans
mesh_terms: D000818:Animals; D001665:Binding Sites; D002403:Cathepsins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002460:Cell Line; D018360:Crystallography, X-Ray; D006801:Humans; D051379:Mice; D009570:Nitriles / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D013329:Structure-Activity Relationship
chemical_list: C553244:6-phenyl-1H-imidazo(4,5-c)pyridine-4-carbonitrile; D009570:Nitriles; D011480:Protease Inhibitors; D011725:Pyridines; D002403:Cathepsins; C028217:cathepsin S