- Discovery and Characterization of CD12681, a Potent RORγ Inverse Agonist, Preclinical Candidate for the Topical Treatment of Psoriasis
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With possible implications in multiple autoimmune diseases, the retinoic acid receptor-related orphan receptor RORγ has become a sought-after target in the pharmaceutical industry. Herein are described the efforts to identify a potent RORγ inverse agonist compatible with topical application for the treatment of skin diseases. These efforts culminated in the discovery of N-(2,4-dimethylphenyl)-N-isobutyl-2-oxo-1-[(tetrahydro-2H-pyran-4-yl)methyl]-2,3-dihydro-1H-benzo[d]imidazole-5-sulfonamide (CD12681), a potent inverse agonist with in vivo activity in an IL-23-induced mouse skin inflammation model.
- Ouvry, Gilles,Atrux-Tallau, Nicolas,Bihl, Franck,Bondu, Aline,Bouix-Peter, Claire,Carlavan, Isabelle,Christin, Olivier,Cuadrado, Marie-Josée,Defoin-Platel, Claire,Deret, Sophie,Duvert, Denis,Feret, Christophe,Forissier, Mathieu,Fournier, Jean-Fran?ois,Froude, David,Hacini-Rachinel, Fériel,Harris, Craig Steven,Hervouet, Catherine,Huguet, Hélène,Lafitte, Guillaume,Luzy, Anne-Pascale,Musicki, Branislav,Orfila, Danielle,Ozello, Benjamin,Pascau, Coralie,Pascau, Jonathan,Parnet, Véronique,Peluchon, Guillaume,Pierre, Romain,Piwnica, David,Raffin, Catherine,Rossio, Patricia,Spiesse, Delphine,Taquet, Nathalie,Thoreau, Etienne,Vatinel, Rodolphe,Vial, Emmanuel,Hennequin, Laurent Fran?ois
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p. 321 - 337
(2018/02/12)
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- MULTIVALENT RAS BINDING COMPOUNDS
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Described herein are compounds that modulate Ras signaling, methods of making such compounds, pharmaceutical compositions and medicaments comprising such compounds, and methods of using such compounds in the treatment of conditions, diseases, or disorders associated with altered Ras signaling. Further described herein are compounds, methods of making such compounds, pharmaceutical compositions and medicaments comprising such compounds and methods of using such compounds in the treatment of cell proliferative disorders, including cancer.
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Paragraph 00853
(2017/07/23)
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- A class of sulfonamide carbonic anhydrase inhibitors with neuropathic pain modulating effects
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A series of benzene sulfonamide carbonic anhydrase (CA, EC 4.2.1.1) inhibitors which incorporate lipophilic 4-alkoxy- and 4-aryloxy moieties, together with several derivatives of ethoxzolamide and sulfanilamide are reported. These derivatives were investi
- Carta, Fabrizio,Di Cesare Mannelli, Lorenzo,Pinard, Melissa,Ghelardini, Carla,Scozzafava, Andrea,McKenna, Robert,Supuran, Claudiu T.
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p. 1828 - 1840
(2015/03/14)
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- BORON-CONTAINING SMALL MOLECULES
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This invention relates to 6-substituted benzoxaborole compounds of the following formula and their use for treating bacterial infections.
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Page/Page column 129
(2011/06/16)
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- INDOLINE SCAFFOLD SHP-2 INHIBITORS AND CANCER TREATMENT METHOD
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The subject invention concerns methods and compounds for inhibiting Shp2. In one embodiment, a compound of the invention has a chemical structure as shown in formula I or II: wherein X, Y, and Z are independently N or S; R1 is cycloalkyl, heter
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Page/Page column 55; 57
(2010/04/03)
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- PYRIMIDINE SULFONAMIDE ANALOGS AND THEIR USE AS AGONISTS OF THE WNT-BETA-CATENIN CELLULAR MESSAGING SYSTEM
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The present invention relates to pyrimidine sulfonamide analogs, methods of making pyrimidine sulfonamide analogs, compositions comprising a pyrimidine sulfonamide analog, and methods for treating canonical Wnt-β-catenin cellular messaging system-related disorders comprising administering to a subject in need thereof an effective amount of a pyrimidine sulfonamide analog.
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Page/Page column 18
(2009/03/07)
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- Optimization of the indolyl quinolinone class of KDR (VEGFR-2) kinase inhibitors: Effects of 5-amido- and 5-sulphonamido-indolyl groups on pharmacokinetics and hERG binding
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Modifications to the basic side-chain of early lead structures of the indolyl quinolinone class of KDR kinase inhibitors resulted in improved pharmacokinetic and ancillary profiles. Specifically, compounds bearing 5-amido- and 5-sulphonamido-indolyl substituents exhibited lower plasma clearance and weaker binding affinity for the IKr potassium channel hERG. 2003 Elsevier Science Ltd. All rights reserved.
- Fraley, Mark E.,Arrington, Kenneth L.,Buser, Carolyn A.,Ciecko, Patrice A.,Coll, Kathleen E.,Fernandes, Christine,Hartman, George D.,Hoffman, William F.,Lynch, Joseph J.,McFall, Rosemary C.,Rickert, Keith,Singh, Romi,Smith, Sheri,Thomas, Kenneth A.,Wong, Bradley K.
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p. 351 - 355
(2007/10/03)
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- Novel diarylsulfonylurea derivatives as potent antimitotic agents
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Novel diarylsulfonylurea derivatives have been synthesized and identified as potent inhibitors of tubulin polymerization and cancer cell proliferation. Furthermore, these compounds were also efficacious against multidrug-resistant cancer cells. A novel series of diarylsulfonylurea derivatives were synthesized and evaluated for interaction with tubulin and for cytotoxicity against human cancer cell lines. These derivatives demonstrated good inhibitory activity against tubulin polymerization, which was well correlated with promising antiproliferative activity as well as G2/M phase cell cycle arrest. Furthermore, several compounds were also efficacious against multidrug-resistant cancer cells, which are resistant to many other known microtubule inhibitors.
- Kim, Semi,Park, Ji Hyun,Koo, Sun-Young,Kim, Jung In,Kim, Min-Hyeung,Kim, Ji Eun,Jo, Kiwon,Geun Choi, Hwan,Lee, Sung Bae,Jung, Sang-Hun
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p. 6075 - 6078
(2007/10/03)
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- ARYLSULFONYLIMIDAZOLONE DERIVATIVES AS AN ANTITUMOR AGENT
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The present invention relates to a novel arylsulfonylimidazolone derivative represented by the following formula (I) which shows a superior antineoplastic activity in contrast to the known sulfonylurea antitumor agents as well as little side effect: and its pharmaceutically acceptable salt and stereoisomer, in which +E,uns - -+EE , R1, and R2 are as defined in the specification.
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