کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1365376 | 981560 | 2008 | 5 صفحه PDF | دانلود رایگان |
As a continuation of our efforts to discover and develop apoptosis inducing 4-aryl-4H-chromenes as novel anticancer agents, we explored modifications at the 2- and 3-positions. It was found that replacement of the 3-cyano group by an ester, including methyl and ethyl ester, resulted in >200-fold reduction of activity. Conversion of the 2-amino group into an amide or urea resulted in 4- to 10-fold drop of activity. Similarly, converting the 2-amino group into a hydrogen resulted in 4- to 10-fold reduction of activity. Compound 3d was highly active with an EC50 value of 29 nM and a GI50 value of 6 nM in T47D cells. Importantly, the 2-H analog 3d was found to be much more stable under acidic conditions compared to the 2-NH2 analog 3b, suggesting that 2-H analogs might have better bioavailability than the 2-NH2 analogs.
The synthesis and SAR of a group of apoptosis inducing 4-aryl-4H-chromenes with modifications at the 2- and 3-positions are reported.Figure optionsDownload as PowerPoint slide
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 18, Issue 2, 15 January 2008, Pages 603–607