کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1356852 981163 2008 17 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Synthesis and evaluation of xanomeline analogs—Probing the wash-resistant phenomenon at the M1 muscarinic acetylcholine receptor
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Synthesis and evaluation of xanomeline analogs—Probing the wash-resistant phenomenon at the M1 muscarinic acetylcholine receptor
چکیده انگلیسی

A series of xanomeline analogs were synthesized and evaluated for binding at the M1 muscarinic acetylcholine receptor (M1 receptor). Specifically, compounds that substitute the O-hexyl chain of xanomeline with polar, ionizable, or conformationally restricted moieties were assessed for their ability to bind to the M1 receptor in a wash-resistant manner (persistent binding). From our screen, several novel ligands that persistently bind to the M1 receptor with greater affinity than xanomeline were discovered. Results indicate that persistent binding may arise not only from hydrophobic interactions but also from ionic interactions with a secondary M1 receptor binding site. Herein, a qualitative model that accounts for both binding scenarios is proposed and applied to understand the structural basis to wash-resistant binding and long-acting effects of xanomeline-based compounds.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 16, Issue 3, 1 February 2008, Pages 1376–1392
نویسندگان
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