کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1399070 1501151 2013 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Synthesis and pharmacological evaluation of 2-aryloxy/arylamino-5-cyanobenzenesulfonylureas as novel thromboxane A2 receptor antagonists
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Synthesis and pharmacological evaluation of 2-aryloxy/arylamino-5-cyanobenzenesulfonylureas as novel thromboxane A2 receptor antagonists
چکیده انگلیسی


• A series of novel 2-aryloxy/arylamino-5-cyanobenzenesulfonylureas were synthesized.
• The newly synthesized compounds were tested in vitro and ex vivo as thromboxane A2 receptor antagonists.
• Some of the tested compounds showed potent thromboxane A2 receptor antagonist activity.
• Three compounds (7e, 7h and 8h) were identified as leads for further pharmacological and toxicological studies.

New series of original 2-aryloxy/arylamino-5-cyanobenzenesulfonylureas were synthesized and evaluated as thromboxane A2 receptor (TP receptor) antagonists. A functional pharmacological test was used, which consisted of measuring the inhibition of intracellular calcium mobilization in a model of mammalian cell line that specifically over-expressed the individual TPα or TPβ isoforms. 2-Arylamino-5-cyanobenzenesulfonylureas exhibited virtually identical affinity and/or functional activity than 2-aryloxy-5-cyanobenzenesulfonylureas for both TPα and TPβ, but some 2-aryloxy-substituted compounds showed increased selectivity for TPβ relative to TPα. Several compounds were found to be as potent as the 2-arylamino-5-nitrobenzenesulfonylurea reference compound BM-573, supporting the view that the bioisosteric replacement of the nitro group by a cyano group was tolerated.TP receptor antagonist activity of the most promising molecules was confirmed in a platelet aggregation assay using the TP receptor agonist U-46619 as a proaggregant.Three compounds (7e, 7h and 8h) were identified as leads for further non-clinical pharmacological and toxicological studies.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Medicinal Chemistry - Volume 65, July 2013, Pages 32–40
نویسندگان
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