کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1360437 981435 2011 15 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Does the combination of optimal substitutions at the C2-, N5- and N8-positions of the pyrazolo-triazolo-pyrimidine scaffold guarantee selective modulation of the human A3 adenosine receptors?
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Does the combination of optimal substitutions at the C2-, N5- and N8-positions of the pyrazolo-triazolo-pyrimidine scaffold guarantee selective modulation of the human A3 adenosine receptors?
چکیده انگلیسی

In an attempt to study the optimal combination of a phenyl ring at the C2-position and different substituents at the N5- and N8-positions towards the selective modulation of human A3 adenosine receptors (hA3AR), we synthesized a new series of 2-para-(un)substituted-phenyl-pyrazolo-triazolo-pyrimidines bearing either a methyl or phenylethyl at N8 and chains of variable length at N5. Through biological evaluation, it was found that the majority of the compounds had good affinities towards the hA3AR in the low nanomolar range. Compound 16 possessed the best hA3AR affinity and selectivity profile (KihA3 = 1.33 nM; hA1/hA3 = 4880; hA2A/hA3 = 1100) in the present series of 2-(substituted)phenyl-pyrazolo-triazolo-pyrimidine derivatives. In addition to pharmacological characterization, a molecular modeling investigation on these compounds further elucidated the effect of different substituents at the pyrazolo-triazolo-pyrimidine scaffold on affinity and selectivity to hA3AR.

Among the newly synthesized 2-(substituted)phenyl-pyrazolo-triazolo-pyrimidine derivatives bearing optimal substitutions at the C2-, N5- and N8-positions, the compound with a 4-chlorophenyl at C2, a small methyl group at N8 and a 4-methoxyphenylcarbamoyl chain at N5 showed the best hA3AR profile, as demonstrated by both pharmacological data and molecular modeling investigations.Figure optionsDownload as PowerPoint slide

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 19, Issue 20, 15 October 2011, Pages 6120–6134
نویسندگان
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