- Raf kinase inhibitor based on chromone structure, and preparation method and uses thereof
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The invention relates to the technical field of pharmaceutical chemistry, and more concretely relates to a group of chromone compounds (A), wherein R1-R10, X1 and X2 are defined in the description. The invention also discloses a preparation method of the
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- Design, synthesis, and biological evaluation of chromone-based p38 MAP kinase inhibitors
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3-(4-Fluorophenyl)-2-(4-pyridyl)chromone derivatives were synthesized and evaluated as p38 MAP kinase inhibitors. Introduction of an amino group in the 2-position of the pyridyl moiety gave p38α inhibitors with IC50 in the low nanomolar range (
- Dyrager, Christine,M?llers, Linda Nilsson,Kj?ll, Linda Karlsson,Alao, John Patrick,Dinér, Peter,Wallner, Fredrik K.,Sunnerhagen, Per,Gr?til, Morten
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p. 7427 - 7431
(2011/12/16)
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- PHARMACEUTICAL COMPOSITIONS FOR THE PREVENTION AND TREATMENT OF COMPLEX DISEASES AND THEIR DELIVERY BY INSERTABLE MEDICAL DEVICES
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The present invention relates to polyphenol-like compounds that are useful for inhibiting VCAM-1 expression, MCP-1 expression and/or SMC proliferation in a mammal. The disclosed compounds are useful for regulating markers of inflammatory conditions, including vascular inflammation, and for treatment and prevention of inflammatory and cardiovascular diseases and related disease states.
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Page/Page column 60
(2008/06/13)
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- Benzoflavone activators of the cystic fibrosis transmembrane conductance regulator: Towards a pharmacophore model for the nucleotide-binding domain
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Our previous screen of flavones and related heterocycles for the ability to activate the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel indicated that UCCF-029, a 7,8-benzoflavone, was a potent activator. In the present study, we describe the synthesis and evaluation, using cell-based assays, of a series of benzoflavone analogues to examine structure-activity relationships and to identify compounds having greater potency for activation of both wild type CFTR and a mutant CFTR (G551D-CFTR) that causes cystic fibrosis in some human subjects. Using UCCF-029 as a structural guide, a panel of 77 flavonoid analogues was prepared. Analysis of the panel in FRT cells indicated that benzannulation of the flavone A-ring at the 7,8-position greatly improved compound activity and potency for several flavonoids. Incorporation of a B-ring pyridyl nitrogen either at the 3- or 4-position also elevated CFTR activity, but the influence of this structural modification was not as uniform as the influence of benzannulation. The most potent new analogue, UCCF-339, activated wild-type CFTR with a Kd of 1.7 μM, which is more active than the previous most potent flavonoid activator of CFTR, apigenin. Several compounds in the benzoflavone panel also activated G551D-CFTR, but none were as active as apigenin. Pharmacophore modeling suggests a common binding mode for the flavones and other known CFTR activators at one of the nucleotide-binding sites, allowing for the rational development of more potent flavone analogues.
- Springsteel, Mark F.,Galietta, Luis J. V.,Ma, Tonghui,By, Kolbot,Berger, Gideon O.,Yang, Hong,Dicus, Christopher W.,Choung, Wonken,Quan, Chao,Shelat, Anang A.,Guy, R. Kiplin,Verkman,Kurth, Mark J.,Nantz, Michael H.
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p. 4113 - 4120
(2007/10/03)
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