Mark P. Sabat | AMiner学者主页

1The Development of Novel Inhibitors of Tumor Necrosis Factor-Alpha (Tnf-Alpha) Production Based on Substituted [5,5]-Bicyclic Pyrazolones

MJ Laufersweiler,TA Brugel,MP Clark, A Goleblowski,RG Bookland,SK Laughlin,MP Sabat,JA Townes,JC VanRens,B De,LC Hsieh,SA Heitmeyer,

Novel substituted [5,5]-bicyclic pyrzazolones are presented as inhibitors of tumor necrosis factor-alpha (TNF-alpha) production. Many of these compounds show low nanomolar activity against lipopolysaccaride (LPS)-induced TNF-alpha production in THP-1 cells. This class of molecules was co-crystallized with mutated p38, and several analogs showed good oral bioavailability in the rat. Oral activity of these compounds in the rat iodoacetate model for osteoarthritis is discussed.

2010Bioorganic & Medicinal Chemistry（2010）引用：20

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2Hck Kinase in Complex with Lck Targetted Inhibitor PG-1009247

R.L. Walter,M.J. Mekel,A.G. Evdokimov,M.E. Pokross,M.P. Sabat

2006

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3The Development of Monocyclic Pyrazolone Based Cytokine Synthesis Inhibitors.

A Golebiowski,Ja Townes,Mj Laufersweiler,Ta Brugel,Mp Clark, Cm Clark,Jf Djung,Sk Laughlin,Mp Sabat,Rg Bookland,Jc Vanrens,B De,

4-Aryl-5-pyrimidyl based cytokine synthesis inhibitors that contain a novel monocyclic, pyrazolone heterocyclic core are described. Many of these inhibitors showed low nanomolar activity against LPS-induced TNF-α production. One of the compounds (6e) was found to be efficacious in the rat iodoacetate (RIA) in vivo model of osteoarthritis. The X-ray crystal structure of a pyrazolone inhibitor cocrystallized with mutated p38 (mp38) is presented.

2005BIOORGANIC & MEDICINAL CHEMISTRY LETTERS（2005）引用：30

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4Crystal Structure Analysis of inactive P38 kinase domain in complex with a Monocyclic Pyrazolone Inhibitor