کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1372440 | 981870 | 2010 | 4 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Addressing species specific metabolism and solubility issues in a quinoline series of oral PDE4 inhibitors Addressing species specific metabolism and solubility issues in a quinoline series of oral PDE4 inhibitors](/preview/png/1372440.png)
Species specific conversion of the lead PDE4 inhibitor 1 to the quinolone 3 was identified as the major route of metabolism in the cynomolgus monkey. Modification of the template to give the cinnoline 9 retained potency and selectivity, and greatly improved the pharmacokinetic profile in the cynomolgus monkey compared with 1. Additional SAR studies aimed at improving the solubility of 9 are also described.
Species specific conversion of the lead PDE4 inhibitor 1 to the quinolone 3 was identified as the major route of metabolism in the cynomolgus monkey. Modification of the template to give the cinnoline 9 retained potency and selectivity, and greatly improved the pharmacokinetic profile in the cynomolgus monkey compared with 1. Additional SAR studies aimed at improving the solubility of 9 are also described.Figure optionsDownload as PowerPoint slide
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 20, Issue 1, 1 January 2010, Pages 137–140