Beyond U0126. Dianion chemistry leading to the rapid synthesis of a series of potent MEK inhibitors
Employing phenylmalonitrile dianion chemistry, a large number of analogues of MEK inhibitor lead SH053 (IC 50=140 nM) were rapidly synthesized leading to single digit nM inhibitors, displaying submicromolar AP-1 transcription inhibition in COS-7 cells. Compound 41, exhibiting a MEK IC 50=12 nM showe...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2004-03, Vol.14 (6), p.1483-1486 |
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| container_title | Bioorganic & medicinal chemistry letters |
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| creator | Wityak, John Hobbs, Frank W. Gardner, Daniel S. Santella, Joseph B. Petraitis, Joseph J. Sun, Jung-Hui Favata, Margaret F. Daulerio, Andrea J. Horiuchi, Kurumi Y. Copeland, Robert A. Scherle, Peggy A. Jaffe, Bruce D. Trzaskos, James M. Magolda, Ronald L. Trainor, George L. Duncia, John V. |
| description | Employing phenylmalonitrile dianion chemistry, a large number of analogues of MEK inhibitor lead SH053 (IC
50=140 nM) were rapidly synthesized leading to single digit nM inhibitors, displaying submicromolar AP-1 transcription inhibition in COS-7 cells. Compound
41, exhibiting a MEK IC
50=12 nM showed ip activity in a TPA-induced ear edema model with an ED
50=5 mg/kg.
Graphic |
| doi_str_mv | 10.1016/j.bmcl.2004.01.012 |
| format | Article |
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50=140 nM) were rapidly synthesized leading to single digit nM inhibitors, displaying submicromolar AP-1 transcription inhibition in COS-7 cells. Compound
41, exhibiting a MEK IC
50=12 nM showed ip activity in a TPA-induced ear edema model with an ED
50=5 mg/kg.
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50=140 nM) were rapidly synthesized leading to single digit nM inhibitors, displaying submicromolar AP-1 transcription inhibition in COS-7 cells. Compound
41, exhibiting a MEK IC
50=12 nM showed ip activity in a TPA-induced ear edema model with an ED
50=5 mg/kg.
Graphic</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Bones, joints and connective tissue. Antiinflammatory agents</subject><subject>Butadienes - chemical synthesis</subject><subject>Cercopithecus aethiops</subject><subject>Chemistry, Pharmaceutical - methods</subject><subject>COS Cells</subject><subject>Enzyme Inhibitors - chemical synthesis</subject><subject>Medical sciences</subject><subject>Mitogen-Activated Protein Kinase Kinases - antagonists & inhibitors</subject><subject>Mitogen-Activated Protein Kinase Kinases - metabolism</subject><subject>Nitriles - chemical synthesis</subject><subject>Pharmacology. 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Dianion chemistry leading to the rapid synthesis of a series of potent MEK inhibitors</title><author>Wityak, John ; Hobbs, Frank W. ; Gardner, Daniel S. ; Santella, Joseph B. ; Petraitis, Joseph J. ; Sun, Jung-Hui ; Favata, Margaret F. ; Daulerio, Andrea J. ; Horiuchi, Kurumi Y. ; Copeland, Robert A. ; Scherle, Peggy A. ; Jaffe, Bruce D. ; Trzaskos, James M. ; Magolda, Ronald L. ; Trainor, George L. ; Duncia, John V.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c450t-17715d04af4a4de91f26a17be8092171be56faa48cbed83bbfdb41da2d506ccd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Bones, joints and connective tissue. 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| subjects | Animals Biological and medical sciences Bones, joints and connective tissue. Antiinflammatory agents Butadienes - chemical synthesis Cercopithecus aethiops Chemistry, Pharmaceutical - methods COS Cells Enzyme Inhibitors - chemical synthesis Medical sciences Mitogen-Activated Protein Kinase Kinases - antagonists & inhibitors Mitogen-Activated Protein Kinase Kinases - metabolism Nitriles - chemical synthesis Pharmacology. Drug treatments Structure-Activity Relationship |
| title | Beyond U0126. Dianion chemistry leading to the rapid synthesis of a series of potent MEK inhibitors |
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