916212-00-5Relevant academic research and scientific papers
Discovery and evaluation of a non-Zn chelating, selective matrix metalloproteinase 13 (MMP-13) inhibitor for potential intra-articular treatment of osteoarthritis
Gege, Christian,Bao, Bagna,Bluhm, Harald,Boer, Jürgen,Gallagher, Brian M.,Korniski, Brian,Powers, Timothy S.,Steeneck, Christoph,Taveras, Arthur G.,Baragi, Vijaykumar M.
, p. 709 - 716 (2012/03/27)
Osteoarthritis (OA) is a nonsystemic disease for which no oral or parenteral disease-modifying osteoarthritic drug (DMOAD) is currently available. Matrix metalloproteinase 13 (MMP-13) has attracted attention as a target with disease-modifying potential because of its major role in tissue destruction associated with OA. Being localized to one or a few joints, OA is amenable to intra-articular (IA) therapy, which has distinct advantages over oral therapies in terms of increasing therapeutic index, by maximizing drug delivery to cartilage and minimizing systemic exposure. Here we report on the synthesis and biological evaluation of a non-zinc binding MMP-13 selective inhibitor, 4-methyl-1-(S)-({5-[(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethyl)carbamoyl] pyrazolo[1,5-a]pyrimidine-7-carbonyl}amino)indan-5-carboxylic acid (1), that is uniquely suited as a potential IA-DMOAD: it has long durability in the joint, penetrates cartilage effectively, exhibits nearly no detectable systemic exposure, and has remarkable efficacy.
HETEROBICYCLIC METALLOPROTEASE INHIBITORS
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Page/Page column 162, (2008/12/05)
The present invention relates generally to heterobicyclic containing pharmaceutical agents, and in particular, to heterobicyclic metalloprotease inhibitor compounds. More particularly, the present invention provides a new class of heterobicyclic metalloprotease inhibiting compounds that exhibit an increased potency in relation to currently known metalloprotease inhibitors.
HETEROBICYCLIC METALLOPROTEASE INHIBITORS
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Page/Page column 232-233, (2008/06/13)
The present invention relates generally to amide group containing pharmaceutical agents, and in particular, to amide containing heterobicyclic metalloprotease inhibitor compounds. More particularly, the present invention provides a new class of heterobicyclic MMP- 13 inhibiting compounds, that exhibit an increased potency in relation to currently known MMP- 13 inhibitors.
