title: Potent, selective, and orally bioavailable matrix metalloproteinase-13 inhibitors for the treatment of osteoarthritis.
abstract: Modification of alpha-biphenylsulfonamidocarboxylic acids led to potent and selective MMP-13 inhibitors. Compound 16 showed 100% oral bioavailability in rats and demonstrated >50% inhibition of bovine cartilage degradation at 10 ng/mL.
authors.affiliation: Department of Chemical and Screening Sciences, Wyeth Research, Cambridge, MA 02140, USA. fhu@wyeth.com
authors.forename: Yonghan
authors.initials: Y
authors.lastname: Hu
authors.forename: Jason S
authors.initials: JS
authors.lastname: Xiang
authors.forename: Martin J
authors.initials: MJ
authors.lastname: DiGrandi
authors.forename: Xuemei
authors.initials: X
authors.lastname: Du
authors.forename: Manus
authors.initials: M
authors.lastname: Ipek
authors.forename: Leif M
authors.initials: LM
authors.lastname: Laakso
authors.forename: Jianchang
authors.initials: J
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Rush
authors.forename: Jean
authors.initials: J
authors.lastname: Schmid
authors.forename: Jerauld S
authors.initials: JS
authors.lastname: Skotnicki
authors.forename: Steve
authors.initials: S
authors.lastname: Tam
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Thomason
authors.forename: Qin
authors.initials: Q
authors.lastname: Wang
authors.forename: Jeremy I
authors.initials: JI
authors.lastname: Levin
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001572:Benzofurans / Q000138:chemical synthesis / Q000737:chemistry; D017364:Collagenases / Q000737:chemistry / Q000378:metabolism*; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D053509:Matrix Metalloproteinase 13; D061965:Matrix Metalloproteinase Inhibitors; D008958:Models, Molecular; D015394:Molecular Structure; D010003:Osteoarthritis / Q000188:drug therapy*; D051381:Rats; D013379:Substrate Specificity
chemical_list: D001572:Benzofurans; D004791:Enzyme Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D017364:Collagenases; D053509:Matrix Metalloproteinase 13; C507083:Mmp13 protein, rat