کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1379376 982027 2005 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Bioisosteric phentolamine analogs as potent α-adrenergic antagonists
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Bioisosteric phentolamine analogs as potent α-adrenergic antagonists
چکیده انگلیسی

The synthesis and biological evaluation of a new series of bioisosteric phentolamine analogs are described. Replacement of the carbon next to the imidazoline ring of phentolamine with a nitrogen atom provides compounds (2, 3) that are about 1.6 times and 4.1 times more potent functionally than phentolamine on rat α1-adrenergic receptors, respectively. In receptor binding assays, the affinities of phentolamine and its bioisosteric analogs were determined on the human embryonic kidney (HEK) and Chinese Hamster ovary (CHO) cell lines expressing the human α1- and α2-AR subtypes, respectively. Analogs 2 and 3, both, displayed higher binding affinities at the α2- versus the α1-ARs, affinities being the least at the α1B-AR. Binding affinities of the methoxy ether analog 2 were greater than those of the phenolic analog 3 at all six α-AR subtypes. One of the nitrogen atoms in the imidazoline ring of phentolamine was replaced with an oxygen atom to give compounds 4 and 5, resulting in a 2-substituted oxazoline ring. The low functional antagonist activity on rat aorta, and binding potencies of these two compounds on human α1A- and α2A-AR subtypes indicate that a basic functional group is important for optimum binding to the α1- and α2A-adrenergic receptors.

The synthesis and biological evaluation of a new series of bioisosteric phentolamine analogs are described.Figure optionsDownload as PowerPoint slide

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 15, Issue 21, 1 November 2005, Pages 4691–4695
نویسندگان
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