- NOVEL OXAZOLE AND THIAZOLE COMPOUNDS AS Β-CATENIN MODULATORS AND USES THEREOF
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Heterocyclic compounds according to formula I: wherein A, B, Y, and Cy are as described herein, are provided as inhibitors of the Wnt pathway that specifically target the activity of the stabilized pool of B-cat. The compounds may be prepared as pharmaceutical compositions, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, cancer, and other conditions related to Wnt pathway dysfunction, including various cancers and pulmonary fibrosis.
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- Parallel Chemistry Approach to Identify Novel Nuclear Receptor Ligands Based on the GW0742 Scaffold
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We describe the parallel synthesis of novel analogs of GW0742, a peroxisome proliferator-activated receptor δ (PPARδ) agonist. For that purpose, modified reaction conditions were applied, such as a solid-phase palladium-catalyzed Suzuki coupling. In addition, tetrazole-based compounds were generated as a bioisostere for carboxylic acid-containing ligand GW0742. The new compounds were investigated for their ability to activate PPARδ mediated transcription and their cross-reactivity with the vitamin D receptor (VDR), another member of the nuclear receptor superfamily. We identified many potent PPARδ agonists that were less toxic than GW0742, where ~65 of the compounds synthesized exhibited partial PPARδ activity (23-98%) with EC50 values ranging from 0.007-18.2 μM. Some ligands, such as compound 32, were more potent inhibitors of VDR-mediated transcription with significantly reduced PPARδ activity than GW0742, however, none of the ligands were completely selective for VDR inhibition over PPARδ activation of transcription.
- Teske, Kelly A.,Rai, Ganesha,Nandhikonda, Premchendar,Sidhu, Preetpal S.,Feleke, Belaynesh,Simeonov, Anton,Yasgar, Adam,Jadhav, Ajit,Maloney, David J.,Arnold, Leggy A.
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supporting information
p. 646 - 656
(2017/10/13)
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- HETEROCYCLIC DERIVATIVES FOR THE TREATMENT OF DISEASES
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The invention relates to compounds of Formula (1) and to processes for the preparation of, intermediates used in the preparation of, compositions containing and the uses of, such derivatives. The compounds according to the present invention are useful in numerous diseases in which ALK protein is involved or in which inhibition of ALK activity may induce benefit, especially for the treatment of cancer mediated by a mutated EML4-ALK fusion protein.
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Page/Page column 107-108
(2011/11/30)
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- NOVEL PHENYLPROPIONIC ACID DERIVATIVES AS PEROXISOME PROLIFERATOR-ACTIVATED GAMMA RECEPTOR MODULATORS, METHOD OF THE SAME, AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME
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The present invention provides a novel phenylpropionic acid derivative and a PPAR-γ modulator comprising the same as an active ingredient. The phenylpropionic acid derivative of the present invention has modulatory action on function of PPAR-γ and then exhibits hypoglycemic, hypolipidemic and insulin resistance-reducing effects on PPAR-mediated diseases or disorders. Therefore, the present invention is prophylactically or therapeutically effective for diabetes and metabolic diseases.
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Page/Page column 31
(2010/04/23)
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- Phenyl-1,2,4-Oxadiazolone Derivatives, Processes For Their Preparation and Methods For Their Use as Pharmaceuticals
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The inventive compounds of the present invention are comprised of phenyl and pyridinyl-1,2,4-oxadiazolone derivatives and their physiologically acceptable salts and functional derivatives that are shown to provide peroxisome proliferator activator recepto
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Page/Page column 96
(2008/12/04)
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- HETEROCYCLIC GPR40 MODULATORS
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The present invention provides compounds useful, for example, for treating metabolic disorders in a subject. Such compounds have the general formula I: where the definitions of the variables are provided herein. The present invention also provides compositions that include, and methods for using, the compounds in preparing medicaments and for treating metabolic disorders such as, for example, type II diabetes.
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Page/Page column 173
(2008/06/13)
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- NOVEL PHENYLPROPIONIC ACID DERIVATIVES AS PEROXISOME PROLIFERATOR-ACTIVATED GAMMA RECEPTOR MODULATORS, METHOD OF THE SAME, AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME
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The present invention provides a novel phenylpropionic acid derivative and a PPAR-γ modulator comprising the same as an active ingredient. The phenylpropionic acid derivative of the present invention has modulatory action on function of PPAR-γ and then exhibits hypoglycemic, hypolipidemic and insulin resistance-reducing effects on PPAR-mediated diseases or disorders. Therefore, the present invention is prophylactically or therapeutically effective for diabetes and metabolic diseases.
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Page/Page column 48; 29
(2008/12/08)
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