1m7q
From Proteopedia
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==Overview== | ==Overview== | ||
| - | The development of potent, orally bioavailable (in rat) and selective | + | The development of potent, orally bioavailable (in rat) and selective dihydroquinazolinone inhibitors of p38alpha MAP kinase is described. These analogues are hybrids of a pyridinylimidazole p38alpha inhibitor reported by Merck Research Laboratories and VX-745. Optimization of the C-5 phenyl and the C-7 piperidinyl substituents led to the identification of 15i which gave excellent suppression of TNF-alpha production in LPS-stimulated whole blood (IC(50)=10nM) and good oral exposure in rats (F=68%, AUCn PO=0.58 microM h). |
==About this Structure== | ==About this Structure== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Cameron, P | + | [[Category: Cameron, P M.]] |
| - | [[Category: Doherty, J | + | [[Category: Doherty, J B]] |
| - | [[Category: Hop, C | + | [[Category: Hop, C E.C A.]] |
| - | [[Category: Keefe, S | + | [[Category: Keefe, S J.O.]] |
[[Category: Liu, L.]] | [[Category: Liu, L.]] | ||
| - | [[Category: Neill, E | + | [[Category: Neill, E A.O.]] |
| - | [[Category: Nichols, E | + | [[Category: Nichols, E A.]] |
| - | [[Category: Patel, S | + | [[Category: Patel, S B.]] |
| - | [[Category: Pivnichny, J | + | [[Category: Pivnichny, J V.]] |
[[Category: Scapin, G.]] | [[Category: Scapin, G.]] | ||
| - | [[Category: Schmatz, D | + | [[Category: Schmatz, D M.]] |
| - | [[Category: Schwartz, C | + | [[Category: Schwartz, C D.]] |
[[Category: Singh, S.]] | [[Category: Singh, S.]] | ||
| - | [[Category: Stelmach, J | + | [[Category: Stelmach, J E.]] |
| - | [[Category: Thompson, C | + | [[Category: Thompson, C M.]] |
[[Category: Wang, Z.]] | [[Category: Wang, Z.]] | ||
| - | [[Category: Zaller, D | + | [[Category: Zaller, D M.]] |
[[Category: DQO]] | [[Category: DQO]] | ||
[[Category: SO4]] | [[Category: SO4]] | ||
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[[Category: serine/threonine kinase]] | [[Category: serine/threonine kinase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:52:26 2008'' |
Revision as of 11:52, 21 February 2008
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Crystal structure of p38 MAP kinase in complex with a dihydroquinazolinone inhibitor
Overview
The development of potent, orally bioavailable (in rat) and selective dihydroquinazolinone inhibitors of p38alpha MAP kinase is described. These analogues are hybrids of a pyridinylimidazole p38alpha inhibitor reported by Merck Research Laboratories and VX-745. Optimization of the C-5 phenyl and the C-7 piperidinyl substituents led to the identification of 15i which gave excellent suppression of TNF-alpha production in LPS-stimulated whole blood (IC(50)=10nM) and good oral exposure in rats (F=68%, AUCn PO=0.58 microM h).
About this Structure
1M7Q is a Single protein structure of sequence from Homo sapiens with and as ligands. Full crystallographic information is available from OCA.
Reference
Design and synthesis of potent, orally bioavailable dihydroquinazolinone inhibitors of p38 MAP kinase., Stelmach JE, Liu L, Patel SB, Pivnichny JV, Scapin G, Singh S, Hop CE, Wang Z, Strauss JR, Cameron PM, Nichols EA, O'Keefe SJ, O'Neill EA, Schmatz DM, Schwartz CD, Thompson CM, Zaller DM, Doherty JB, Bioorg Med Chem Lett. 2003 Jan 20;13(2):277-80. PMID:12482439
Page seeded by OCA on Thu Feb 21 13:52:26 2008
Categories: Homo sapiens | Single protein | Cameron, P M. | Doherty, J B | Hop, C E.C A. | Keefe, S J.O. | Liu, L. | Neill, E A.O. | Nichols, E A. | Patel, S B. | Pivnichny, J V. | Scapin, G. | Schmatz, D M. | Schwartz, C D. | Singh, S. | Stelmach, J E. | Thompson, C M. | Wang, Z. | Zaller, D M. | DQO | SO4 | Atp-binding domain | Inhibitor | Serine/threonine kinase
