کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10585935 | 981382 | 2011 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Electron-donating para-methoxy converts a benzamide-isoquinoline derivative into a highly Sigma-2 receptor selective ligand
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
The sigma-2 (Ï2) receptor has been suggested to be a promising target for pharmacological interventions to curb tumor progression. Development of Ï2-specific ligands, however, has been hindered by lack of understanding of molecular determinants that underlie selective ligand-Ï2 interactions. Here we have explored effects of electron donating and withdrawing groups on ligand selectivity for the Ï2 versus Ï1 receptor using new benzamide-isoquinoline derivatives. The electron-donating methoxy group increased but the electron-withdrawing nitro group decreased Ï2 affinity. In particular, an extra methoxy added to the para-position (5e) of the benzamide phenyl ring of 5f dramatically improved (631 fold) the Ï2 selectivity relative to the Ï1 receptor. This para-position provided a sensitive site for effective manipulation of the sigma receptor subtype selectivity using either the methoxy or nitro substituent. Our study provides a useful guide for further improving the Ï2-over-Ï1 selectivity of new ligands.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 19, Issue 24, 15 December 2011, Pages 7435-7440
Journal: Bioorganic & Medicinal Chemistry - Volume 19, Issue 24, 15 December 2011, Pages 7435-7440
نویسندگان
Abdol R. Hajipour, Lian-Wang Guo, Arindam Pal, Timur Mavlyutov, Arnold E. Ruoho,