title: Thioether acetamides as P3 binding elements for tetrahydropyrido-pyrazole cathepsin S inhibitors.
abstract: A series of tetrahydropyrido-pyrazole cathepsin S (CatS) inhibitors with thioether acetamide functional groups were prepared with the goal of improving upon the cellular activity of amidoethylthioethers. This Letter describes altered amide connectivity, in conjunction with changes to other binding elements, resulting in improved potency, as well as increased knowledge of the relationship between this chemotype and human CatS activity.
authors.affiliation: Johnson & Johnson Pharmaceutical Research & Development, L.L.C., 3210 Merryfield Row, San Diego, CA 92121, United States. dwiener@its.jnj.com
authors.forename: Danielle K
authors.initials: DK
authors.lastname: Wiener
authors.forename: Alice
authors.initials: A
authors.lastname: Lee-Dutra
authors.forename: Scott
authors.initials: S
authors.lastname: Bembenek
authors.forename: Steven
authors.initials: S
authors.lastname: Nguyen
authors.forename: Robin L
authors.initials: RL
authors.lastname: Thurmond
authors.forename: Siquan
authors.initials: S
authors.lastname: Sun
authors.forename: Lars
authors.initials: L
authors.lastname: Karlsson
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Grice
authors.forename: Todd K
authors.initials: TK
authors.lastname: Jones
authors.forename: James P
authors.initials: JP
authors.lastname: Edwards
mesh_terms: D000081:Acetamides / Q000737:chemistry / Q000494:pharmacology*; D002403:Cathepsins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D008958:Models, Molecular; D011480:Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D011720:Pyrazoles / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013440:Sulfides / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000081:Acetamides; D011480:Protease Inhibitors; D011720:Pyrazoles; D013440:Sulfides; C031280:pyrazole; D002403:Cathepsins; C028217:cathepsin S