- Discovery, Structure-Activity Relationship, and Binding Mode of an Imidazo[1,2-a]pyridine Series of Autotaxin Inhibitors
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Autotaxin (ATX) is a secreted enzyme playing a major role in the production of lysophosphatidic acid (LPA) in blood through hydrolysis of lysophosphatidyl choline (LPC). The ATX-LPA signaling axis arouses a high interest in the drug discovery industry as it has been implicated in several diseases including cancer, fibrotic diseases, and inflammation, among others. An imidazo[1,2-a]pyridine series of ATX inhibitors was identified out of a high-throughput screening (HTS). A cocrystal structure with one of these compounds and ATX revealed a novel binding mode with occupancy of the hydrophobic pocket and channel of ATX but no interaction with zinc ions of the catalytic site. Exploration of the structure-activity relationship led to compounds displaying high activity in biochemical and plasma assays, exemplified by compound 40. Compound 40 was also able to decrease the plasma LPA levels upon oral administration to rats.
- Joncour, Agnès,Desroy, Nicolas,Housseman, Christopher,Bock, Xavier,Bienvenu, Natacha,Cherel, La?titia,Labeguere, Virginie,Peixoto, Christophe,Annoot, Denis,Lepissier, Luce,Heiermann, J?rg,Hengeveld, Willem Jan,Pilzak, Gregor,Monjardet, Alain,Wakselman, Emanuelle,Roncoroni, Veronique,Le Tallec, Sandrine,Galien, René,David, Christelle,Vandervoort, Nele,Christophe, Thierry,Conrath, Katja,Jans, Mia,Wohlkonig, Alexandre,Soror, Sameh,Steyaert, Jan,Touitou, Robert,Fleury, Damien,Vercheval, Lionel,Mollat, Patrick,Triballeau, Nicolas,Van Der Aar, Ellen,Brys, Reginald,Heckmann, Bertrand
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- COMPOUNDS AS CASEIN KINASE INHIBITORS
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Provided are novel casein kinase inhibitors, or pharmaceutically acceptable salts thereof. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermediates are also provided.
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Paragraph 00310-00313
(2021/10/02)
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- METHODS FOR INHIBITING CASEIN KINASES
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The present disclosure provides methods for inhibiting CK1 delta or CK1 epsilon activity, comprising administering an effective amount of the compound of Formula (I) to (IV), or a pharmaceutically acceptable salt thereof.
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Paragraph 00192-00194
(2021/10/02)
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- INHIBITORS OF HISTONE DEACETYLASE
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ABSTRACT OF THE DISCLOSURE This invention relates to compounds and methods for the inhibition of HDAC enzymatic activity. More particularly, the invention provides for compounds of formula (I), (I) and N-oxides, hydrates, solvates, pharmaceutically acceptable salts, prodrugs and complexes thereof, and racemic and scalemic mixtures, diastereomers and enantiomers thereof, wherein L, M, n, R, W, X and Y are as defined in the specification.
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Page/Page column 93; 94
(2009/06/27)
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- Synthesis and biological activity of imidazopyridine anticoccidial agents: Part I
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Coccidiosis is the major cause of morbidity and mortality in the poultry industry. Protozoan parasites of the genus Eimeria invade the intestinal lining of the avian host causing tissue pathology, poor weight gain, and in some cases mortality. Resistance
- Scribner, Andrew,Dennis, Richard,Hong, Jean,Lee, Shuliang,McIntyre, Donald,Perrey, David,Feng, Dennis,Fisher, Michael,Wyvratt, Matthew,Leavitt, Penny,Liberator, Paul,Gurnett, Anne,Brown, Chris,Mathew, John,Thompson, Donald,Schmatz, Dennis,Biftu, Tesfaye
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p. 1334 - 1357
(2008/09/17)
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- Hybrid-designed inhibitors of p38 MAP kinase utilizing N-arylpyridazinones
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Imidazo[1,2-α]pyridyl N-arylpyridazinones were hybridized from the classic pyridinylimidazoles and the more recent dual hydrogen bond acceptors, resulting in a new structural class of selective p38 MAP kinase inhibitors.
- Colletti, Steven L.,Frie, Jessica L.,Dixon, Elizabeth C.,Singh, Suresh B.,Choi, Bernard K.,Scapin, Giovanna,Fitzgerald, Catherine E.,Kumar, Sanjeev,Nichols, Elizabeth A.,O'Keefe, Stephen J.,O'Neill, Edward A.,Porter, Gene,Samuel, Koppara,Schmatz, Dennis M.,Schwartz, Cheryl D.,Shoop, Wesley L.,Thompson, Chris M.,Thompson, James E.,Wang, Ruixiu,Woods, Andrea,Zaller, Dennis M.,Doherty, James B.
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p. 349 - 352
(2007/10/03)
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