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- W2087919544 abstract "A series of potent chiral PDE5 inhibitors are described that are based on the sildenafil architecture but exhibit much greater selectivity over PDE6. Eudismic analysis of the SAR in this series provided a clear illustration of Pfeiffer’s rule and indicated that the chiral motif was involved in a highly-stereoselective interaction with PDE5. This PDE5 specificity translated to levels of selectivity over PDE6 that were hitherto unprecedented in the sildenafil scaffold. UK-371,800 (compound 8) was identified as a development candidate from this series that married sildenafil-like molecular properties with high selectivity over PDE6. Clinical data confirm that UK-371,800 has markedly superior human pharmacokinetics to a previously-described higher molecular weight achiral analogue in this template (compound 1)." @default.
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- W2087919544 date "2008-12-01" @default.
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- W2087919544 title "Highly potent and selective chiral inhibitors of PDE5: An illustration of Pfeiffer’s rule" @default.
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- W2087919544 doi "https://doi.org/10.1016/j.bmcl.2008.10.037" @default.
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