1628260-79-6Relevant articles and documents
Discovery of 2-[[2-Ethyl-6-[4-[2-(3-hydroxyazetidin-1-yl)-2-oxoethyl]piperazin-1-yl]-8-methylimidazo[1,2-a]pyridin-3-yl]methylamino]-4-(4-fluorophenyl)thiazole-5-carbonitrile (GLPG1690), a First-in-Class Autotaxin Inhibitor Undergoing Clinical Evaluation for the Treatment of Idiopathic Pulmonary Fibrosis
Desroy, Nicolas,Housseman, Christopher,Bock, Xavier,Joncour, Agnès,Bienvenu, Natacha,Cherel, La?titia,Labeguere, Virginie,Rondet, Emilie,Peixoto, Christophe,Grassot, Jean-Marie,Picolet, Olivier,Annoot, Denis,Triballeau, Nicolas,Monjardet, Alain,Wakselman, Emanuelle,Roncoroni, Veronique,Le Tallec, Sandrine,Blanque, Roland,Cottereaux, Celine,Vandervoort, Nele,Christophe, Thierry,Mollat, Patrick,Lamers, Marieke,Auberval, Marielle,Hrvacic, Boska,Ralic, Jovica,Oste, Line,Van der Aar, Ellen,Brys, Reginald,Heckmann, Bertrand
, p. 3580 - 3590 (2017)
Autotaxin is a circulating enzyme with a major role in the production of lysophosphatic acid (LPA) species in blood. A role for the autotaxin/LPA axis has been suggested in many disease areas including pulmonary fibrosis. Structural modifications of the known autotaxin inhibitor lead compound 1, to attenuate hERG inhibition, remove CYP3A4 time-dependent inhibition, and improve pharmacokinetic properties, led to the identification of clinical candidate GLPG1690 (11). Compound 11 was able to cause a sustained reduction of LPA levels in plasma in vivo and was shown to be efficacious in a bleomycin-induced pulmonary fibrosis model in mice and in reducing extracellular matrix deposition in the lung while also reducing LPA 18:2 content in bronchoalveolar lavage fluid. Compound 11 is currently being evaluated in an exploratory phase 2a study in idiopathic pulmonary fibrosis patients.
COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR THE TREATMENT OF INFLAMMATORY DISORDERS
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, (2014/09/29)
The present invention discloses compounds according to Formula I: Wherein R1a, R1b, R2, R4, R5, R6a, R6b, R7, R8, W, X, Cy, and the subscript a are as defined herein. The present invention relates to compounds inhibiting autotaxin (NPP2 or ENPP2), methods for their production, pharmaceutical compositions comprising the same, and methods of treatment using the same, for the prophylaxis and/or treatment of diseases involving fibrotic diseases, proliferative diseases, inflammatory diseases, autoimmune diseases, respiratory diseases, cardiovascular diseases, neurodegenerative diseases, dermatological disorders, and/or abnormal angiogenesis associated diseasesby administering the compound of the invention.