Synthesis and biological evaluation of ((4-keto)-phenoxy)methyl biphenyl-4-sulfonamides: a class of potent aggrecanase-1 inhibitors.
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.
Hopper
Darrin W
DW
Department of Chemical and Screening Sciences, Wyeth Research, 401 North Middletown Road, Pearl River, NY 10965, USA.
Vera
Matthew D
MD
How
David
D
Sabatini
Joshua
J
Xiang
Jason S
JS
Ipek
Manus
M
Thomason
Jennifer
J
Hu
Yonghan
Y
Feyfant
Eric
E
Wang
Qin
Q
Georgiadis
Katy E
KE
Reifenberg
Erica
E
Sheldon
Richard T
RT
Keohan
Cristin C
CC
Majumdar
Manas K
MK
Morris
Elisabeth A
EA
Skotnicki
Jerauld
J
Sum
Phaik-Eng
PE