title: SAR studies of non-zinc-chelating MMP-13 inhibitors: improving selectivity and metabolic stability.
abstract: SAR studies to improve the selectivity and metabolic stability of a class of recently discovered MMP-13 inhibitors are reported. Improved selectivity was achieved by modifying interactions with the S1' pocket. Metabolic stability was improved through reduction of inhibitor lipophilicity. This translated into lower in vivo clearance for the preferred compound.
authors.affiliation: Department of Medicinal Chemistry, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT 06877, USA. amy.gao@boehringer-ingelheim.com
authors.forename: Donghong Amy
authors.initials: DA
authors.lastname: Gao
authors.forename: Zhaoming
authors.initials: Z
authors.lastname: Xiong
authors.forename: Alexander
authors.initials: A
authors.lastname: Heim-Riether
authors.forename: Laura
authors.initials: L
authors.lastname: Amodeo
authors.forename: E Michael
authors.initials: EM
authors.lastname: August
authors.forename: Xianhua
authors.initials: X
authors.lastname: Cao
authors.forename: Leonard
authors.initials: L
authors.lastname: Ciccarelli
authors.forename: Brandon K
authors.initials: BK
authors.lastname: Collins
authors.forename: Kyle
authors.initials: K
authors.lastname: Harrington
authors.forename: Kathleen
authors.initials: K
authors.lastname: Haverty
authors.forename: Melissa
authors.initials: M
authors.lastname: Hill-Drzewi
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.forename: Shuang
authors.initials: S
authors.lastname: Liang
authors.forename: Steluta Mariana
authors.initials: SM
authors.lastname: Margarit
authors.forename: Neil
authors.initials: N
authors.lastname: Moss
authors.forename: Nelamangala
authors.initials: N
authors.lastname: Nagaraja
authors.forename: John
authors.initials: J
authors.lastname: Proudfoot
authors.forename: Rene
authors.initials: R
authors.lastname: Roman
authors.forename: Sabine
authors.initials: S
authors.lastname: Schlyer
authors.forename: Lana Smith
authors.initials: LS
authors.lastname: Keenan
authors.forename: Steven
authors.initials: S
authors.lastname: Taylor
authors.forename: Bernd
authors.initials: B
authors.lastname: Wellenzohn
authors.forename: Dieter
authors.initials: D
authors.lastname: Wiedenmayer
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Neil A
authors.initials: NA
authors.lastname: Farrow
mesh_terms: D002614:Chelating Agents / Q000737:chemistry / Q000494:pharmacology; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D015032:Zinc / Q000737:chemistry
chemical_list: D002614:Chelating Agents; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D015032:Zinc