کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1374624 | 981922 | 2010 | 6 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Addressing time-dependent CYP 3A4 inhibition observed in a novel series of substituted amino propanamide renin inhibitors, a case study Addressing time-dependent CYP 3A4 inhibition observed in a novel series of substituted amino propanamide renin inhibitors, a case study](/preview/png/1374624.png)
Time-dependent inhibitors of CYPs have the potential to perpetrate drug–drug interactions in the clinical setting. After finding that several leading compounds in a novel series of substituted amino propanamide renin inhibitors inactivated CYP3A4 in an NADPH-dependent and time-dependent manner, a search to identify the cause of this liability was initiated. Extensive SAR revealed that the amide bridge present in compound 1 as a possible culprit. Through the installation of a metabolic soft spot distal to this moiety, potent renin inhibitors with improved CYP profile were identified.
The identification of a possible culprit responsible for compound (1)’s time-dependent CYP 3A4 inhibition as well as suitable solution are described therein.Figure optionsDownload as PowerPoint slide
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 20, Issue 17, 1 September 2010, Pages 5074–5079