1229607-47-9Relevant academic research and scientific papers
1-Pyrazolyl-3-(4-((2-anilinopyrimidin-4-yl)oxy)napththalen-1-yl)ureas as p38 MAP kinase inhibitors
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Paragraph 0086; 0087, (2013/04/23)
There are provided compounds of formula (I) which are inhibitors of the family of p38 mitogen-activated protein kinase enzymes, and to their use in therapy, including in pharmaceutical combinations, especially in the treatment of inflammatory diseases, in
Design and synthesis of inhaled p38 inhibitors for the treatment of chronic obstructive pulmonary disease
Millan, David S.,Bunnage, Mark E.,Burrows, Jane L.,Butcher, Kenneth J.,Dodd, Peter G.,Evans, Timothy J.,Fairman, David A.,Hughes, Samantha J.,Kilty, Iain C.,Lemaitre, Arnaud,Lewthwaite, Russell A.,Mahnke, Axel,Mathias, John P.,Philip, James,Smith, Robert T.,Stefaniak, Mark H.,Yeadon, Michael,Phillips, Christopher
supporting information; experimental part, p. 7797 - 7814 (2012/01/05)
This paper describes the identification and optimization of a novel series of DFG-out binding p38 inhibitors as inhaled agents for the treatment of chronic obstructive pulmonary disease. Structure based drug design and "inhalation by design" principles have been applied to the optimization of the lead series exemplied by compound 1a. Analogues have been designed to be potent and selective for p38, with an emphasis on slow enzyme dissociation kinetics to deliver prolonged lung p38 inhibition. Pharmacokinetic properties were tuned with high intrinsic clearance and low oral bioavailability in mind, to minimize systemic exposure and reduce systemically driven adverse events. High CYP mediated clearance and glucuronidation were targeted to achieve high intrinsic clearance coupled with multiple routes of clearance to minimize drug-drug interactions. Furthermore, pharmaceutical properties such as stability, crystallinity, and solubility were considered to ensure compatibility with a dry powder inhaler. 1ab (PF-03715455) was subsequently identified as a clinical candidate from this series with efficacy and safety profiles confirming its potential as an inhaled agent for the treatment of COPD.
RESPIRATORY FORMULATIONS AND COMPOUNDS FOR USE THEREIN
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Page/Page column 55-56, (2012/01/06)
The present invention relates to respiratory formulations comprising a compound of formula (I): and use of said compounds and compositions in treatment, for example in the treatment of an inflammatory disease or a respiratory disorder, in particular an inflammatory mediated and/or virally mediated respiratory disorder such as asthma and COPD or the treatment or prevention of viral infection, for example infection by influenza virus, rhinovirus or RSV. The invention also extends to certain novel compounds of formula (I).
P38 MAP KINASE INHIBITORS
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Page/Page column 60-61, (2010/07/02)
The present disclosure relates to compounds of formula (I): which are inhibitors of p38 mitogen-activated protein kinase enzymes,particularly the alpha and gamma kinase sub-types thereof, and their use in therapy, including in pharmaceutical combinations, especially in the treatment of inflammatory diseases, including inflammatory diseases of the lung, such as COPD
