کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1371649 981849 2010 4 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Design, synthesis and structure–activity relationship of novel quinoxalin-2-carboxamides as 5-HT3 receptor antagonists for the management of depression
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Design, synthesis and structure–activity relationship of novel quinoxalin-2-carboxamides as 5-HT3 receptor antagonists for the management of depression
چکیده انگلیسی

A novel series of quinoxalin-2-carboxamides were designed based on the ligand-based approach, employing a three-point pharmacophore model; it consists of an aromatic residue and a linking carbonyl group and a basic nitrogen. The target new chemical entities were synthesized from the key intermediate, quinoxalin-2-carboxylic acid, by coupling it with various amines in the presence of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC·HCl) and 1-hydroxybenzotriazole (HOBt). The obtained compounds’ structures were confirmed by spectral data. The target new chemical entities were evaluated for their 5-HT3 receptor antagonisms in longitudinal muscle myenteric plexus preparation from guinea pig ileum against 5-HT3 agonist, 2-methyl-5-HT, which was expressed in the form of pA2 value. All the synthesized compounds showed antagonism towards 5-HT3 receptor; based on this result, a structure–activity relationship was derived, which reveals that the aromatic residue in 5-HT3 receptor antagonists may have hydrophobic interaction with 5-HT3 receptor. Regardless of their antagonistic potentials, all the synthesized molecules were screened for their anti-depressant potentials by using forced swim test in mice model; interestingly none of the tested compounds affect the locomotion of mice in the tested dose levels. Compounds with significant pA2 values exhibited good anti-depressant-like activity as compared to the vehicle-treated group.

Synthesis, 5-HT3 receptor antagonistic and anti-depressant-like activity of novel quinoxalin-2-carboxamides are described.Figure optionsDownload as PowerPoint slide

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 20, Issue 22, 15 November 2010, Pages 6773–6776
نویسندگان
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