کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1378218 | 981996 | 2005 | 6 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Structure–activity relationship study of novel necroptosis inhibitors Structure–activity relationship study of novel necroptosis inhibitors](/preview/png/1378218.png)
Necroptosis is a regulated caspase-independent cell death mechanism that results in morphological features resembling necrosis. It can be induced in a FADD-deficient variant of human Jurkat T cells treated with TNF-α. 5-(1H-Indol-3-ylmethyl)-2-thiohydantoins and 5-(1H-indol-3-ylmethyl)hydantoins were found to be potent necroptosis inhibitors (called necrostatins). A SAR study revealed that several positions of the indole were intolerant of substitution, while small substituents at the 7-position resulted in increased inhibitory activity. The hydantoin ring was also quite sensitive to structural modifications. A representative member of this compound class demonstrated moderate pharmacokinetic characteristics and readily entered the central nervous system upon intravenous administration.
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Journal: Bioorganic & Medicinal Chemistry Letters - Volume 15, Issue 22, 15 November 2005, Pages 5039–5044