کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1373195 | 981893 | 2007 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
The discovery of 2-anilinothiazolones as 11β-HSD1 inhibitors
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کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
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چکیده انگلیسی
A series of 2-anilinothiazolones were prepared as inhibitors of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). The most potent compounds contained a 2-chloro or 2-fluoro group on the aniline ring with an isopropyl substituent on the 5-position of the thiazolone ring (compounds 2 and 3, respectively). The binding mode was determined through the X-ray co-crystal structure of the enzyme with compound 3. This compound was also ∼70-fold selective over 11β-HSD2 and was orally bioavailable in rat pharmacokinetic studies. However, compound 3 was >580-fold less active in the 11β-HSD1 cell assay when tested in the presence of 3% human serum albumin.
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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 17, Issue 22, 15 November 2007, Pages 6056–6061
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 17, Issue 22, 15 November 2007, Pages 6056–6061
نویسندگان
Chester Yuan, David J. St. Jean Jr., Qingyian Liu, Lynn Cai, Aiwen Li, Nianhe Han, George Moniz, Ben Askew, Randall W. Hungate, Lars Johansson, Lars Tedenborg, David Pyring, Meredith Williams, Clarence Hale, Michelle Chen, Rod Cupples, Jiandong Zhang,