5-Amino-pyrazoles as potent and selective p38a inhibitors
The synthesis and structure-activity relationships (SAR) of p38a MAP kinase inhibitors based on a 5-amino-pyrazole scaffold are described. These studies led to the identification of compound 2j as a potent and selective inhibitor of p38a MAP kinase with excellent cellular potency toward the inhibiti...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2010-12, Vol.20 (23), p.6886-6889 |
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| container_end_page | 6889 |
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| container_issue | 23 |
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| container_title | Bioorganic & medicinal chemistry letters |
| container_volume | 20 |
| creator | Das, Jagabandhu Moquin, Robert V Dyckman, Alaric J Li, Tianle Pitt, Sidney Zhang, Rosemary Shen, Ding Ren McIntyre, Kim W Gillooly, Kathleen Doweyko, Arthur M Newitt, John A Sack, John S Zhang, Hongjian Kiefer, Susan E Kish, Kevin McKinnon, Murray Barrish, Joel C Dodd, John H Schieven, Gary L Leftheris, Katerina |
| description | The synthesis and structure-activity relationships (SAR) of p38a MAP kinase inhibitors based on a 5-amino-pyrazole scaffold are described. These studies led to the identification of compound 2j as a potent and selective inhibitor of p38a MAP kinase with excellent cellular potency toward the inhibition of TNFa production. Compound 2j was highly efficacious in vivo in inhibiting TNFa production in an acute murine model of TNFa production. X-ray co-crystallography of a 5-amino-pyrazole analog 2f bound to unphosphorylated p38a is also disclosed. |
| doi_str_mv | 10.1016/j.bmcl.2010.10.034 |
| format | Article |
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| identifier | ISSN: 0960-894X |
| ispartof | Bioorganic & medicinal chemistry letters, 2010-12, Vol.20 (23), p.6886-6889 |
| issn | 0960-894X |
| language | eng |
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| source | Elsevier ScienceDirect Journals Complete |
| subjects | Animal models |
| title | 5-Amino-pyrazoles as potent and selective p38a inhibitors |
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