کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1373001 981887 2013 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
A novel series of N-(azetidin-3-yl)-2-(heteroarylamino)acetamide CCR2 antagonists
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
A novel series of N-(azetidin-3-yl)-2-(heteroarylamino)acetamide CCR2 antagonists
چکیده انگلیسی

The inflammatory response associated with the activation of C–C chemokine receptor CCR2 via it’s interaction with the monocyte chemoattractant protein-1 (MCP-1, CCL2) has been implicated in many disease states, including rheumatoid arthritis, multiple sclerosis, atherosclerosis, asthma and neuropathic pain. Small molecule antagonists of CCR2 have been efficacious in animal models of inflammatory disease, and have been advanced into clinical development. The necessity to attenuate hERG binding appears to be a common theme for many of the CCR2 antagonist scaffolds appearing in the literature, presumably due the basic hydrophobic motif present in all of these molecules. Following the discovery of a novel cyclohexyl azetidinylamide CCR2 antagonist scaffold, replacement of the amide bond with heterocyclic rings was explored as a strategy for reducing hERG binding and improving pharmacokinetic properties.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 23, Issue 4, 15 February 2013, Pages 1063–1069
نویسندگان
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