کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1394946 1501094 2016 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Synthesis and structure–activity relationships of novel arylpiperazines as potent antagonists of α1-adrenoceptor
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Synthesis and structure–activity relationships of novel arylpiperazines as potent antagonists of α1-adrenoceptor
چکیده انگلیسی


• 11 new phenylpiperazines derived from LASSBio 772 has been designed and synthesized.
• Affinities for human α1-AR subtypes in radioligand binding assays were assessed.
• Antagonist profiles at α1-AR subtypes in functional bioassays were evaluated.
• Among the newly synthesized compounds, potent ligands were identified.
• SAR-analysis identified new hits for further search for improved α1-AR agents.

Arylpiperazines 2–11 were synthesized, and their biological profiles at α1-adrenergic receptors (α1-ARs) assessed by binding assays in CHO cells expressing human cloned subtypes and by functional experiments in isolated rat vas deferens (α1A), spleen (α1B), and aorta (α1D). Modifications at the 1,3-benzodioxole and phenyl phamacophoric units resulted in the identification of a number of potent compounds (moderately selective with respect to the α1b-AR), in binding experiments. Notably, compound 7 (LDT451) showed a subnanomolar pKi of 9.41 towards α1a-AR. An encouragingly lower α1B-potency was a general trend for all the series of compounds, which showed α1A/D over α1B selectivity in functional assays. If adequately optimized, such peculiar selectivity could have relevance for a potential LUTS/BPH therapeutic application.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Medicinal Chemistry - Volume 122, 21 October 2016, Pages 601–610
نویسندگان
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