کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1364781 981545 2008 4 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Effect of B-ring substitution pattern on binding mode of propionamide selective androgen receptor modulators
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Effect of B-ring substitution pattern on binding mode of propionamide selective androgen receptor modulators
چکیده انگلیسی

Selective androgen receptor modulators (SARMs) are essentially prostate sparing androgens, which provide therapeutic potential in osteoporosis, male hormone replacement, and muscle wasting. Herein we report crystal structures of the androgen receptor (AR) ligand-binding domain (LBD) complexed to a series of potent synthetic nonsteroidal SARMs with a substituted pendant arene referred to as the B-ring. We found that hydrophilic B-ring para-substituted analogs exhibit an additional region of hydrogen bonding not seen with steroidal compounds and that multiple halogen substitutions affect the B-ring conformation and aromatic interactions with Trp741. This information elucidates interactions important for high AR binding affinity and provides new insight for structure-based drug design.

Figure optionsDownload as PowerPoint slide

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 18, Issue 20, 15 October 2008, Pages 5567–5570
نویسندگان
, , , , , , , , , ,