کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1358256 981328 2014 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Alkynyl–coumarinyl ethers as MAO-B inhibitors
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Alkynyl–coumarinyl ethers as MAO-B inhibitors
چکیده انگلیسی

In this study, alkynyl–coumarinyl ethers were developed as inhibitors of human monoamine oxidase B (MAO-B). A series of 31 new, ether-connected coumarin derivatives was synthesized via hydroxycoumarins, whose phenolic group at position 6, 7 or 8 was converted by means of the Mitsunobu reaction. The majority of the final products were produced from primary alcohols with a terminal alkyne group. The inhibitors were optimized with respect to the structure of the alkynyloxy chain and its position at the fused benzene ring as well as the residue at position 3 of the pyran-2H-one part. A hex-5-ynyloxy chain at position 7 was found to be particular advantageous. Among the 7-hex-5-ynyloxy-coumarins, the 3-methoxycarbonyl derivative 36 was characterized as a dual-acting inhibitor with IC50 values of less than 10 nM towards MAO-A and MAO-B, and the 3-(4-methoxy)phenyl derivative 44 was shown to combine strong anti-MAO-B potency (IC50 = 3.0 nM) and selectivity for MAO-B over MAO-A (selectivity >3400-fold).

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 22, Issue 6, 15 March 2014, Pages 1916–1928
نویسندگان
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