1415823-65-2Relevant academic research and scientific papers
Discovery of Evobrutinib: An Oral, Potent, and Highly Selective, Covalent Bruton's Tyrosine Kinase (BTK) Inhibitor for the Treatment of Immunological Diseases
Askew, Ben C.,Bender, Andrew T.,Brugger, Nadia,Caldwell, Richard D.,Camps, Montserrat,Dhanabal, Mohanraj,Dutt, Vikram,Eichhorn, Thomas,Follis, Ariele Viacava,Gardberg, Anna S.,Goutopoulos, Andreas,Grenningloh, Roland,Head, Jared,Healey, Brian,Hodous, Brian L.,Huck, Bayard R.,Johnson, Theresa L.,Jones, Christopher,Jones, Reinaldo C.,Liu-Bujalski, Lesley,Meyring, Michael,Mochalkin, Igor,Morandi, Federica,Nguyen, Ngan,Potnick, Justin R.,Qiu, Hui,Santos, Dusica Cvetinovic,Schmidt, Ralf,Sherer, Brian,Shutes, Adam,Urbahns, Klaus,Wegener, Ansgar A.,Zimmerli, Simone C.
, (2019/09/06)
Bruton's tyrosine kinase (BTK) inhibitors such as ibrutinib hold a prominent role in the treatment of B cell malignancies. However, further refinement is needed to this class of agents, particularly in terms of adverse events (potentially driven by kinase promiscuity), which preclude their evaluation in nononcology indications. Here, we report the discovery and preclinical characterization of evobrutinib, a potent, obligate covalent inhibitor with high kinase selectivity. Evobrutinib displayed sufficient preclinical pharmacokinetic and pharmacodynamic characteristics which allowed for in vivo evaluation in efficacy models. Moreover, the high selectivity of evobrutinib for BTK over epidermal growth factor receptor and other Tec family kinases suggested a low potential for off-target related adverse effects. Clinical investigation of evobrutinib is ongoing in several autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosus.
COMPOSITIONS AND METHODS FOR THE PRODUCTION OF PYRIMIDINE AND PYRIDINE COMPOUNDS WITH BTK INHIBITORY ACTIVITY
-
, (2013/02/27)
The present invention provides novel pyrimidine and pyridine compounds according to Formula (I), Formula (II), Formula (III), Formula (IV) and Formula (V) their manufacture and use for the treatment of hyperproliferative diseases including, but not limite
