1159113-33-3Relevant academic research and scientific papers
Design and synthesis of long acting inhaled corticosteroids for the treatment of asthma
Millan, David S.,Ballard, Stephen A.,Chunn, Sara,Dybowski, Joseph A.,Fulton, Craig K.,Glossop, Paul A.,Guillabert, Edouard,Hewson, Christopher A.,Jones, Rhys M.,Lamb, David J.,Napier, Carolyn M.,Payne-Cook, Toby A.,Renery, Emmanuelle R.,Selby, Matthew D.,Tutt, Michelle F.,Yeadon, Michael
, p. 5826 - 5830 (2011/10/18)
In this Letter we present data for a novel series of ICS for the treatment of asthma. 'Inhalation by design' principles have been applied to a series of highly potent steroidal GR agonists, with a focus on optimising the potential therapeutic index in human. Pharmacokinetic properties were tuned with high intrinsic clearance and low oral bioavailability in mind, to minimise systemic exposure and reduce systemically driven adverse events. High CYP mediated clearance as well as glucuronidation were targeted to achieve high intrinsic clearance coupled with multiple routes of clearance to minimise drug-drug interactions. Furthermore, pharmaceutical properties such as stability, crystallinity and solubility were considered to ensure compatibility with a dry powder inhaler. This work culminated in the identification of the clinical candidate 15, which demonstrates preclinically the desired efficacy and safety profiles confirming its potential as an inhaled agent for the treatment of asthma.
NOVEL GLUCOCORTICOID RECEPTOR AGONISTS
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Page/Page column 43-44, (2009/07/03)
This invention relates to novel glucocorticoid receptor agonists of formula (I) and to processes and intermediates for their preparation. The present invention also relates to pharmaceutical compositions containing these compounds, to their combination with one or more other therapeutic agents, as well as to their use for the treatment of a number of inflammatory and allergic diseases, disorders and conditions.
