beta-N-Biaryl ether sulfonamide hydroxamates as potent gelatinase inhibitors: part 1. Design, synthesis, and lead identification.
A new series of beta-N-biaryl ether sulfonamide hydroxamates as novel gelatinase inhibitors is described. These compounds exhibit good potency for MMP-2 and MMP-9 without inhibiting MMP-1. The structure-activity relationships (SAR) reveal the biaryl ether type P1' moiety together with methanesulfonamide is the optimal combination that provides inhibitory activity of MMP-9 in the single-digit nanomolar range.
Yang
Shyh-Ming
SM
Johnson & Johnson Pharmaceutical Research and Development, L.L.C., 8 Clarke Drive, Cranbury, NJ 08512, USA. syang9@prdus.jnj.com
Scannevin
Robert H
RH
Wang
Bingbing
B
Burke
Sharon L
SL
Wilson
Lawrence J
LJ
Karnachi
Prabha
P
Rhodes
Kenneth J
KJ
Lagu
Bharat
B
Murray
William V
WV
D000818:Animals; D015195:Drug Design; D018093:Gelatinases / Q000037:antagonists & inhibitors*; D006801:Humans; D006877:Hydroxamic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D061965:Matrix Metalloproteinase Inhibitors; D008862:Microsomes, Liver / Q000187:drug effects; D015394:Molecular Structure; D011719:Pyrazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
C097658:CGS 27023A; D006877:Hydroxamic Acids; D061965:Matrix Metalloproteinase Inhibitors; D011719:Pyrazines; D013449:Sulfonamides; D018093:Gelatinases