کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10583704 981298 2014 14 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Design, synthesis and evaluation of 2-aminothiazole derivatives as sphingosine kinase inhibitors
ترجمه فارسی عنوان
طراحی، ترکیب و ارزیابی مشتقات 2-آمینوتیازول به عنوان مهار کننده های اسپینگزین کیناز
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
چکیده انگلیسی
Sphingosine kinases (SphK1, SphK2) are main regulators of sphingosine-1-phosphate (S1P), which is a pleiotropic lipid mediator involved in numerous physiological and pathophysiological functions. SphKs are targets for novel anti-cancer and anti-inflammatory agents that can promote cell apoptosis and modulate autoimmune diseases. Herein, we describe the design, synthesis and evaluation of an aminothiazole class of SphK inhibitors. Potent inhibitors have been discovered through a series of modifications using the known SKI-II scaffold to define structure-activity relationships. We identified N-(4-methylthiazol-2-yl)-(2,4′-bithiazol)-2′-amine (24, ST-1803; IC50 values: 7.3 μM (SphK1), 6.5 μM (SphK2)) as a promising candidate for further in vivo investigations and structural development.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 22, Issue 19, 1 October 2014, Pages 5354-5367
نویسندگان
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