Syntheses and in vitro evaluation of arylsulfone-based MMP inhibitors with heterocycle-derived zinc-binding groups (ZBGs).
Several classes of arylsulfone-based MMP-2/-9 inhibitors utilizing 6- to 8-membered heterocyclic rings as zinc-binding groups (ZBGs) have been synthesized and their enzyme inhibitory activities were evaluated. Although a number of 6- and 7-membered heterocycles were effective, the most potent arylsulfone inhibitors are based on the rigid 1- or 3-hydroxypyridone ZBG.
Zhang
Yue-Mei
YM
East Coast Research and Early Development, Johnson & Johnson Pharmaceutical Research and Development, Welsh & McKean Roads, Spring House, PA 19477, USA. yzhang5@prdus.jnj.com
Fan
Xiaodong
X
Yang
Shyh-Ming
SM
Scannevin
Robert H
RH
Burke
Sharon L
SL
Rhodes
Kenneth J
KJ
Jackson
Paul F
PF
D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D007769:Lactams / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011728:Pyridones / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013450:Sulfones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015032:Zinc / Q000737:chemistry*
D006571:Heterocyclic Compounds; D007769:Lactams; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D011728:Pyridones; D013450:Sulfones; D015032:Zinc