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PDBsum entry 1m7q
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Design and synthesis of potent, Orally bioavailable dihydroquinazolinone inhibitors of p38 map kinase.
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Authors
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J.E.Stelmach,
L.Liu,
S.B.Patel,
J.V.Pivnichny,
G.Scapin,
S.Singh,
C.E.Hop,
Z.Wang,
J.R.Strauss,
P.M.Cameron,
E.A.Nichols,
S.J.O'Keefe,
E.A.O'Neill,
D.M.Schmatz,
C.D.Schwartz,
C.M.Thompson,
D.M.Zaller,
J.B.Doherty.
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Ref.
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Bioorg Med Chem Lett, 2003,
13,
277-280.
[DOI no: ]
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PubMed id
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Abstract
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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).
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