title: Arylamine based cathepsin K inhibitors: investigating P3 heterocyclic substituents.
abstract: A modification of novel cathepsin K inhibitors I was carried out. The structural design was aimed at reducing the lipophilic character of compounds I for obtaining better pharmacokinetic profiles. This modification afforded several less lipophilic compounds with good inhibitory activities and pharmacokinetic profiles, although the enzyme selectivity over cathepsin S was left at issue.
authors.affiliation: Medicinal Chemistry Research Laboratories, Sankyo Co., Ltd, Shinagawa-ku, Tokyo 140-8710, Japan. sinozu@sankyo.co.jp
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Shinozuka
authors.forename: Kousei
authors.initials: K
authors.lastname: Shimada
authors.forename: Satoshi
authors.initials: S
authors.lastname: Matsui
authors.forename: Takahiro
authors.initials: T
authors.lastname: Yamane
authors.forename: Mayumi
authors.initials: M
authors.lastname: Ama
authors.forename: Takeshi
authors.initials: T
authors.lastname: Fukuda
authors.forename: Motohiko
authors.initials: M
authors.lastname: Taki
authors.forename: Yuko
authors.initials: Y
authors.lastname: Takeda
authors.forename: Eri
authors.initials: E
authors.lastname: Otsuka
authors.forename: Michiko
authors.initials: M
authors.lastname: Yamato
authors.forename: Satoru
authors.initials: S
authors.lastname: Naito
mesh_terms: D000588:Amines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002401:Cathepsin B / Q000037:antagonists & inhibitors; D056657:Cathepsin K; D056668:Cathepsin L; D002403:Cathepsins / Q000037:antagonists & inhibitors*; D003546:Cysteine Endopeptidases; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008968:Molecular Conformation; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000588:Amines; D004791:Enzyme Inhibitors; D006571:Heterocyclic Compounds; D011994:Recombinant Proteins; D002403:Cathepsins; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; C534281:CTSL protein, human; D056668:Cathepsin L; C028217:cathepsin S; C534130:CTSK protein, human; D056657:Cathepsin K