- NOVEL GLUCOCORTICOID RECEPTOR AGONISTS
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This invention relates to novel glucocorticoid receptor agonists of formula (I) and to processes and intermediates for their preparation. The present invention also relates to pharmaceutical compositions containing these compounds, to their combination with one or more other therapeutic agents, as well as to their use for the treatment of a number of inflammatory and allergic diseases, disorders and conditions.
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Page/Page column 49-50
(2010/12/26)
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- Design, synthesis, and evaluation of orally active benzimidazoles and benzoxazoles as vascular endothelial growth factor-2 receptor tyrosine kinase inhibitors
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Inhibition of the VEGF signaling pathway has become a valuable approach in the treatment of cancers. Guided by X-ray crystallography and molecular modeling, a series of 2-aminobenzimidazoles and 2-aminobenzoxazoles were identified as potent inhibitors of VEGFR-2 (KDR) in both enzymatic and HUVEC cellular proliferation assays. In this report we describe the synthesis and structure-activity relationship of a series of 2-aminobenzimidazoles and benzoxazoles, culminating in the identification of benzoxazole 22 as a potent and selective VEGFR-2 inhibitor displaying a good pharmacokinetic profile. Compound 22 demonstrated efficacy in both the murine matrigel model for vascular permeability (79% inhibition observed at 100 mg/kg) and the rat corneal angiogenesis model (ED50 = 16.3 mg/kg).
- Potashman, Michele H.,Bready, James,Coxon, Angela,Demelfi Jr., Thomas M.,DiPietro, Lucian,Doerr, Nicholas,Elbaum, Daniel,Estrada, Juan,Gallant, Paul,Germain, Julie,Gu, Yan,Harmange, Jean-Christophe,Kaufman, Stephen A.,Kendall, Rick,Kim, Joseph L.,Kumar, Gondi N.,Long, Alexander M.,Neervannan, Seshadri,Patel, Vinod F.,Polverino, Anthony,Rose, Paul,Van Der Plas, Simon,Whittington, Douglas,Zanon, Roger,Zhao, Huilin
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p. 4351 - 4373
(2008/02/13)
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- FUSED AZOLES SUCH AS 2,5-DISUBSTITUTED BENZIMIDAZOLES, BENZOXAZOLES AND BENZOTHIAZOLES AS KINASE INHIBITORS
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The invention relates to compounds of the formulae (I) to (III) wherein the substituents are as defined in the specification. These compounds have kinase inhibitory activity, such as VEGFR/KDR inhibitory activity. Accordingly, the compounds of the formulae (I) to (III) would be useful in the prevention and treatment of angiogenesis related disorders, ophthalmological conditions, proliferative diseases, inflammatory diseases, and other pathological conditions as described in the specification.
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- SUBSTITUTED PHENOXY-AMINOPROPANOLS
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Substituted phenoxy-aminopropanols of the formula STR1 wherein R is a branched-chain alkyl of 3 or 4 carbon atoms, R 1 is hydrogen, halogen or lower alkyl and R 2 and R 3, independently, are hydrogen, halogen, lower alkyl, lower alkoxy or lower alkylthio, and pharmaceutically acceptable acid addition salts thereof, are described. A process for their preparation, as well as pharmaceutical preparations containing them are also described. The compounds of formula I and their salts possess cardioselective β-adrenergic blocking activity and antihypertensive activity.
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- β1-Selective Adrenoceptor Antagonists. 2. 4-Ether-Linked Phenoxypropanolamines
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A series of 4-substituted phenoxypropanolamines was prepared and examined for β-adrenoceptor activity.Some of the compounds, especially the oxy>ethoxy>phenoxy>propanolamines (14, 15, and 24), showed potent β1-blo
- Machin, Peter J.,Hurst, David N.,Bradshaw, Rachel M.,Blaber, Leslie C.,Burden, David T.,et al.
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p. 1570 - 1576
(2007/10/02)
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