title: Syntheses and in vitro evaluation of arylsulfone-based MMP inhibitors with heterocycle-derived zinc-binding groups (ZBGs).
abstract: 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.
authors.affiliation: East Coast Research and Early Development, Johnson & Johnson Pharmaceutical Research and Development, Welsh & McKean Roads, Spring House, PA 19477, USA. yzhang5@prdus.jnj.com
authors.forename: Yue-Mei
authors.initials: YM
authors.lastname: Zhang
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Fan
authors.forename: Shyh-Ming
authors.initials: SM
authors.lastname: Yang
authors.forename: Robert H
authors.initials: RH
authors.lastname: Scannevin
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Burke
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Rhodes
authors.forename: Paul F
authors.initials: PF
authors.lastname: Jackson
mesh_terms: 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*
chemical_list: D006571:Heterocyclic Compounds; D007769:Lactams; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D011728:Pyridones; D013450:Sulfones; D015032:Zinc