title: Pyrazole-based arylalkyne cathepsin S inhibitors. Part III: modification of P4 region.
abstract: Novel classes of tetrahydropyrido-pyrazole thioether amines and arylalkynes that display potency against human Cathepsin S have been previously reported. Here, key pharmacophoric elements of these two classes are merged, and SAR investigations of the P4 region are described, in conjunction with re-optimization of the P5 and P1/P1'/P3 regions. Identification of meta-substituted arylalkynes with good potency and improved solubility is described.
authors: Janssen Research & Development, L.L.C., 3210 Merryfield Row, San Diego, CA 92121, USA. Jwiener1@its.jnj.com
authors: John J M
authors: JJ
authors: Wiener
authors: Alvah Tyson
authors: AT
authors: Wickboldt
authors: Steven
authors: S
authors: Nguyen
authors: Siquan
authors: S
authors: Sun
authors: Raymond
authors: R
authors: Rynberg
authors: Michele
authors: M
authors: Rizzolio
authors: Lars
authors: L
authors: Karlsson
authors: James P
authors: JP
authors: Edwards
authors: Cheryl A
authors: CA
authors: Grice
mesh_terms: D000480:Alkynes / Q000737:chemistry* / Q000494:pharmacology*; D002403:Cathepsins / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D006801:Humans; D011720:Pyrazoles / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000480:Alkynes; D011720:Pyrazoles; D002403:Cathepsins; C028217:cathepsin S