کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10591509 981754 2013 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Construction and functionalization of pyranone ring fused with pyran moiety: Design and synthesis of novel pyrano[4,3-b]pyran-5(4H)-ones as potential inhibitors of sirtuins
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Construction and functionalization of pyranone ring fused with pyran moiety: Design and synthesis of novel pyrano[4,3-b]pyran-5(4H)-ones as potential inhibitors of sirtuins
چکیده انگلیسی
Novel pyrano[4,3-b]pyran-5(4H)-one based small molecules were designed as potential inhibitors of sirtuins (i.e., yeast sir2, a homolog of human SIRT1). Elegant synthesis of these compounds was performed via a multi-step sequence consisting of MCR, Sandmeyer type iodination, Sonogashira type coupling followed by iodocyclization and then Pd-mediated various C-C bond forming reactions. The overall strategy involved the construction of a pyran ring followed by the fused pyranone moiety and subsequent functionalization at C-8 position of the resultant core pyrano[4,3-b]pyran-5(4H)-one framework. The crystal structure analysis of a representative iodolactonized product (6d) is presented. Some of the synthesized compounds showed promising inhibitory activities when tested against yeast sir2 in vitro. The compound 6g showed dose dependent inhibition (IC50 = 78.05 μM) of yeast sir2 and good interactions with this protein in silico.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 23, Issue 14, 15 July 2013, Pages 4195-4205
نویسندگان
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