کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1359879 981418 2009 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Design and synthesis of novel dihydroquinoline-3-carboxylic acids as HIV-1 integrase inhibitors
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Design and synthesis of novel dihydroquinoline-3-carboxylic acids as HIV-1 integrase inhibitors
چکیده انگلیسی

Previously, we discovered linomide analogues as novel HIV-1 integrase (IN) inhibitors. Here, to make possible structure–activity relationships, we report on the design and synthesis of a series of substituted dihydroquinoline-3-carboxylic acids. The crystal structure of the representative compound 2c has also been solved. Among the eight new analogues, 2e showed a potency in inhibiting IN strand transfer catalytic activity similar to the reference diketo acid inhibitor L-731,988 (IC50 = 0.9 μM vs. 0.54 μM, for 2e and L-731,988, respectively). Furthermore, none of the compounds showed significant cytotoxicity in two tested cancer cell lines. These compounds represent an interesting prototype of IN inhibitors, potentially involved in a metal chelating mechanism, and further optimization is warranted.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 17, Issue 7, 1 April 2009, Pages 2925–2935
نویسندگان
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