- Addressing hERG activity while maintaining favorable potency, selectivity and pharmacokinetic properties of PPARδ modulators
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One of the most commonly used strategies to reduce hERG (human ether-a-go-go) activity in the drug candidates is introduction of a carboxylic acid group. During the optimization of PPARδ modulators, some of the compounds containing a carboxylic acid were found to inhibit the hERG channel in a patch clamp assay. By modifying the basicity of the imidazole core, potent and selective PPARδ modulators that do not inhibit hERG channel were identified. Some of the modulators have excellent pharmacokinetic profiles in mice.
- Lagu, Bharat,Senaiar, Ramesh S.,Kluge, Arthur F.,Mallesh,Ramakrishna,Bhat, Raveendra,Patane, Michael A.
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- PPAR AGONISTS, COMPOUNDS, PHARMACEUTICAL COMPOSITIONS, AND METHODS OF USE THEREOF
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Provided herein are compounds and compositions useful in increasing PPAR8 activity. The compounds and compositions provided herein are useful for the treatment of PPAR8 related diseases (e.g., muscular diseases, vascular disease, demyelinating disease, and metabolic diseases).
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- PPAR AGONISTS, COMPOUNDS, PHARMACEUTICAL COMPOSITIONS, AND METHODS OF USE THEREOF
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Provided herein are compounds and compositions useful in increasing PPARδ activity. The compounds and compositions provided herein are useful for the treatment of PPARδ related diseases (e.g., muscular diseases, vascular disease, demyelinating disease, and metabolic diseases).
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- COMPOUNDS FOR TREATMENT OF CANCER
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The present invention relates to pharmaceutical compositions for treating cancer comprising BRAF inhibitors, (e.g. vemurafenib) and/or MEK inhibitor, (e.g. trametinib, RO5068760), in combination with anti-tubulin compounds of the invention or other known tubulin inhibitors, and using such compositions for treating cancer such as melanoma, drug-resistant cancer, and cancer metastasis.
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Paragraph 00223; 00246
(2014/09/29)
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- COMPOUNDS FOR TREATMENT OF CANCER
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The present invention relates to novel compounds having anti-cancer activity, methods of making these compounds, and their use for treating cancer and drug-resistant tumors, e.g. melanoma, metastatic melanoma, drug resistant melanoma, prostate cancer and drug resistant prostate cancer.
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Paragraph 0041; 00356
(2011/10/03)
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- PTERIDINONES AS INHIBITORS OF POLO - LIKE KINASE
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The present invention provides compounds having a structure according to Formula (I) or a salt or solvate thereof, wherein ring A, X, R1, R2, R3, R4, R5 and R6, are defined herein. The invention further provides pharmaceutical compositions including the compounds of the invention and methods of making and using the compounds and compositions of the invention, e.g., in the treatment and prevention of various disorders, such as Parkinson's disease.
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Page/Page column 107
(2011/07/09)
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- Novel imidazole derivatives
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The invention is concerned with novel imidazole derivatives of formula (I), wherein m, E, R1, R2, R3, R4, R5, R6 and R7 are as defined in the description and in the claims, as we
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Page/Page column 45
(2009/01/23)
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- A simple and convenient one-pot method for the preparation of heteroaryl-2-imidazoles from nitriles
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A simple, convenient and high-yielding one-pot method for the synthesis of 2-heterocycle-substituted imidazoles from the corresponding nitriles has been developed. The procedure is easily scaleable and the workup does not involve chromatography. This synthesis is also applicable to the preparation of imidazoles with electron-poor aryl substituents.
- Voss, Matthew E.,Beer, Catherine M.,Mitchell, Scott A.,Blomgren, Peter A.,Zhichkin, Paul E.
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p. 645 - 651
(2008/04/12)
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- Efficient and highly regioselective direct C-2 arylation of azoles, including free (NH)-imidazole, -benzimidazole and -indole, with aryl halides
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The Pd- and Cu-mediated reaction of a large variety of π-electron sufficient heteroarenes, which include free (NH)-imidazoles, -benzimidazole and -indole, with aryl iodides under ligandless and base-free conditions provides regioselectively the required 2-arylheterocycle derivatives in high yields. 2-Aryl-1-phenyl-1H-imidazoles can also be prepared by a one-pot domino HALEX and Pd- and Cu-mediated arylation reactions of 1-phenyl-1H-imidazole with activated and unactivated aryl bromides under base-free and ligandless conditions. The protocol for the synthesis of 2-arylazoles involving the use of aryl iodides has been found to be suitable for the efficient preparation of three bioactive compounds and a key intermediate in the synthesis of a heparanase inhibitor.
- Bellina, Fabio,Calandri, Chiara,Cauteruccio, Silvia,Rossi, Renzo
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p. 1970 - 1980
(2007/10/03)
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- Palladium- and copper-mediated direct C-2 arylation of azoles - Including free (NH)-imidazole, -benzimidazole and -indole - Under base-free and ligandless conditions
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The first palladium- and copper-mediated C-2 arylations of thiazole, oxazole, N-methylimidazole and N-arylimidazoles, as well as of free (NH)-imidazole, -benzimidazole and -indole, with aryl iodides under ligandless and base-free conditions are described. Complete selectivity has been achieved under these unprecedented conditions, which allow the use of substrates containing base-sensitive groups, such the NH groups of imidazole, benzimidazole or indole, without their prior protection. No N-arylation products were detected in the arylation of free (NH)-imidazole, -benzimidazole and -indole. Wiley-VCH Verlag GmbH & Co. KGaA, 2006.
- Bellina, Fabio,Cauteruccio, Silvia,Rossi, Renzo
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p. 1379 - 1382
(2007/10/03)
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- New one-step synthesis of 2-aryl-1H-imidazoles: Dehydrogenation of 2-aryl-δ2-imidazolines with dimethylsulfoxide
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A new one-step method for the preparation of 2-aryl-1Himidazoles 3, based on the DMSO dehydrogenation of 2-aryl-Δ2-imidazolines, is described. A comparative study between DMSO and 10% Pd/C, the best known catalyst employed in this transformation, has also been developed. Both protocols were carried out at 120 °C for 48 hours.
- Anastassiadou,Baziard-Mouysset,Payard
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p. 1814 - 1816
(2007/10/03)
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