title: Synthesis and biological evaluation of ((4-keto)-phenoxy)methyl biphenyl-4-sulfonamides: a class of potent aggrecanase-1 inhibitors.
abstract: The prevention of aggrecan (a key component of cartilage) cleavage via the inhibition of aggrecanase-1 may provide a unique opportunity to stop the progression of cartilage degradation in osteoarthritis. The evaluation of a series of biphenylsulfonamides resulted in the identification of the ((4-keto)-phenoxy)methyl biphenyl-4-sulfonamides analogs (19-21 and 24) with improved Agg-1 inhibition and MMP-2, MMP-13 activity.
authors.affiliation: Department of Chemical and Screening Sciences, Wyeth Research, 401 North Middletown Road, Pearl River, NY 10965, USA.
authors.forename: Darrin W
authors.initials: DW
authors.lastname: Hopper
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Vera
authors.forename: David
authors.initials: D
authors.lastname: How
authors.forename: Joshua
authors.initials: J
authors.lastname: Sabatini
authors.forename: Jason S
authors.initials: JS
authors.lastname: Xiang
authors.forename: Manus
authors.initials: M
authors.lastname: Ipek
authors.forename: Jennifer
authors.initials: J
authors.lastname: Thomason
authors.forename: Yonghan
authors.initials: Y
authors.lastname: Hu
authors.forename: Eric
authors.initials: E
authors.lastname: Feyfant
authors.forename: Qin
authors.initials: Q
authors.lastname: Wang
authors.forename: Katy E
authors.initials: KE
authors.lastname: Georgiadis
authors.forename: Erica
authors.initials: E
authors.lastname: Reifenberg
authors.forename: Richard T
authors.initials: RT
authors.lastname: Sheldon
authors.forename: Cristin C
authors.initials: CC
authors.lastname: Keohan
authors.forename: Manas K
authors.initials: MK
authors.lastname: Majumdar
authors.forename: Elisabeth A
authors.initials: EA
authors.lastname: Morris
authors.forename: Jerauld
authors.initials: J
authors.lastname: Skotnicki
authors.forename: Phaik-Eng
authors.initials: PE
authors.lastname: Sum