title: 3,4-Disubstituted benzofuran P1' MMP-13 inhibitors: optimization of selectivity and reduction of protein binding.
abstract: Potent 3,4-disubstituted benzofuran P1' MMP-13 inhibitors have been prepared. Selectivity over MMP-2 was achieved through a substituent at the C4 position of the benzofuran P1' moiety of the molecule. By replacing a backbone benzene with a pyridine and valine with threonine, compounds (e.g., 44) with greatly reduced plasma protein binding were also obtained.
authors.affiliation: Department of Chemical Sciences, Wyeth Research, 200 CambridgePark Drive, Cambridge, MA 02140, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Yonghan
authors.initials: Y
authors.lastname: Hu
authors.forename: Jianchang
authors.initials: J
authors.lastname: Li
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Thomason
authors.forename: Dianne
authors.initials: D
authors.lastname: DeVincentis
authors.forename: Xuemei
authors.initials: X
authors.lastname: Du
authors.forename: Junjun
authors.initials: J
authors.lastname: Wu
authors.forename: Rajeev
authors.initials: R
authors.lastname: Hotchandani
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Rush
authors.forename: Jerauld S
authors.initials: JS
authors.lastname: Skotnicki
authors.forename: Steve
authors.initials: S
authors.lastname: Tam
authors.forename: Priya S
authors.initials: PS
authors.lastname: Chockalingam
authors.forename: Elisabeth A
authors.initials: EA
authors.lastname: Morris
authors.forename: Jeremy I
authors.initials: JI
authors.lastname: Levin
mesh_terms: D000818:Animals; D001572:Benzofurans / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011485:Protein Binding; D011817:Rabbits; D012709:Serum Albumin / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D001572:Benzofurans; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D012709:Serum Albumin; D053509:Matrix Metalloproteinase 13; D020778:Matrix Metalloproteinase 2