Efficacious Inhaled PDE4 Inhibitors
with Low Emetic Potential and Long Duration of Action for the Treatment
of COPD
Posted on 2014-06-12 - 00:00
Oral
phosphodiesterase 4 (PDE4) inhibitors, such as cilomilast and roflumilast,
have been shown to be efficacious against chronic obstructive pulmonary
disease (COPD). However, these drugs have been hampered by mechanism-related
side effects such as nausea and emesis at high doses. Compounds administered
by inhalation are delivered directly to the site of action and may
improve the therapeutic index required to overcome side effects. This
paper describes systematic and rational lead optimization to deliver
highly potent, long-acting, and efficacious preclinical inhaled PDE4
inhibitors with low emetic potential.
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Savi, Chris De; Cox, Rhona J.; Warner, Daniel J.; Cook, Anthony
R.; Dickinson, Mark R.; McDonough, Amy; et al. (2016). Efficacious Inhaled PDE4 Inhibitors
with Low Emetic Potential and Long Duration of Action for the Treatment
of COPD. ACS Publications. Collection. https://doi.org/10.1021/jm5001216Â
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AUTHORS (13)
- CSChris De SaviRCRhona J. CoxDWDaniel J. WarnerACAnthony R. CookMDMark R. DickinsonAMAmy McDonoughLMLouis C. MorrillBPBeth ParkerGAGlen AndrewsSYSimon S. YoungPGPeter S. GilmourRRRob RileyMDMatthew S. Dearman
