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- W1551695736 abstract "In this chapter, we provide a brief summary of prototypical Phosphodiesterase-4 (PDE4) inhibitors and focus on recent medicinal chemistry efforts to address the dose-limiting adverse events associated with PDE4 therapeutic agents. Roflumilast, the first PDE4 inhibitor to gain FDA approval, and Apremilast, set to come to market in 2014, demonstrate that it is possible to achieve a therapeutic window with pan-PDE4 inhibitors. Additional strategies discussed herein include designing inhibitors with subtype selectivity, allosteric modulation, tissue targeting, and polypharmacology. It is unclear which, if any, of these strategies discussed will further increase the therapeutic window in humans. The potential of these strategies to mitigate adverse events while providing therapeutic benefit will have to be determined in the clinic." @default.
- W1551695736 created "2016-06-24" @default.
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- W1551695736 creator A5073669283 @default.
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- W1551695736 date "2014-04-23" @default.
- W1551695736 modified "2023-09-23" @default.
- W1551695736 title "PDE4: Recent Medicinal Chemistry Strategies to Mitigate Adverse Effects" @default.
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- W1551695736 doi "https://doi.org/10.1002/9783527682348.ch04" @default.
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