Thioether acetamides as P3 binding elements for tetrahydropyrido-pyrazole cathepsin S inhibitors.
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.
Wiener
Danielle K
DK
Johnson & Johnson Pharmaceutical Research & Development, L.L.C., 3210 Merryfield Row, San Diego, CA 92121, United States. dwiener@its.jnj.com
Lee-Dutra
Alice
A
Bembenek
Scott
S
Nguyen
Steven
S
Thurmond
Robin L
RL
Sun
Siquan
S
Karlsson
Lars
L
Grice
Cheryl A
CA
Jones
Todd K
TK
Edwards
James P
JP
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*
D000081:Acetamides; D011480:Protease Inhibitors; D011720:Pyrazoles; D013440:Sulfides; C031280:pyrazole; D002403:Cathepsins; C028217:cathepsin S