کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1376835 981966 2008 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Structure-based design of novel groups for use in the P1 position of thrombin inhibitor scaffolds. Part 2: N-acetamidoimidazoles
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Structure-based design of novel groups for use in the P1 position of thrombin inhibitor scaffolds. Part 2: N-acetamidoimidazoles
چکیده انگلیسی

Guided by X-ray crystallography of thrombin-inhibitor complexes and molecular modeling, alkylation of the N1 nitrogen of the imidazole P1 ligand of the pyridinoneacetamide thrombin inhibitor 1 with various acetamide moieties furnished inhibitors with significantly improved thrombin potency, trypsin selectivity, functional in vitro anticoagulant potency and in vivo antithrombotic efficacy. In the pyrazinoneacetamide series, oral bioavailability was also improved.

Alkylation of the N1 nitrogen of the imidazole P1 ligand of the pyridoneacetamide thrombin inhibitor 1 (RH) with various acetamide moieties furnished inhibitors (RCH2CONHR′) with significantly improved thrombin potency, trypsin selectivity, functional in vitro anticoagulant potency, and in vivo antithrombotic efficacy.Figure optionsDownload as PowerPoint slide

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 18, Issue 6, 15 March 2008, Pages 2062–2066
نویسندگان
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