کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1377361 | 981976 | 2008 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Hepatoselectivity of statins: Design and synthesis of 4-sulfamoyl pyrroles as HMG-CoA reductase inhibitors
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کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
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چکیده انگلیسی
4-Sulfamoyl pyrroles were designed as novel hepatoselective HMG-CoA reductase inhibitors (statins) to reduce myalgia, a statin-induced adverse effect. The compounds were prepared via a [3 + 2] cycloaddition of a Münchnone with a sulfonamide-substituted alkyne. We identified compounds with greater selectivity for hepatocytes compared to L6-myocytes than rosuvastatin and atorvastatin. There was an inverse correlation of myocyte potencies and C log P values. A number of analogs were effective at reducing cholesterol in acute and chronic in vivo models but they lacked sufficient chronic in vivo activity to warrant further development.
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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 18, Issue 3, 1 February 2008, Pages 1151–1156
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 18, Issue 3, 1 February 2008, Pages 1151–1156
نویسندگان
William K.C. Park, Robert M. Kennedy, Scott D. Larsen, Steve Miller, Bruce D. Roth, Yuntao Song, Bruce A. Steinbaugh, Kevin Sun, Bradley D. Tait, Mark C. Kowala, Bharat K. Trivedi, Bruce Auerbach, Valerie Askew, Lisa Dillon, Jeffrey C. Hanselman,