کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1373182 981891 2011 4 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
P3 optimization of functional potency, in vivo efficacy and oral bioavailability in 3-aminopyrazinone thrombin inhibitors bearing non-charged groups at the P1 position
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
P3 optimization of functional potency, in vivo efficacy and oral bioavailability in 3-aminopyrazinone thrombin inhibitors bearing non-charged groups at the P1 position
چکیده انگلیسی

Although the S3 pocket of the thrombin active site is lined with lipophilic amino acid residues, the accommodation of polarity within the lipophilic P3 moiety of small molecule inhibitors is possible provided that the polar functionality is capable of pointing away from the binding pocket outwards toward solvent while simultaneously allowing the lipophilic portion of the P3 ligand to interact with the S3 amino acid residues. Manipulation of this motif provided the means to effect optimization of functional potency, in vivo antithrombotic efficacy and oral bioavailability in a series of 3-aminopyrazinone thrombin inhibitors which contained non-charged groups at the P1 position.

A series of 3-aminopyrazinone P2 thrombin inhibitors bearing non-charged groups (X, Y) at the P1 benzylamino position was optimized with respect to functional potency, in vivo efficacy and oral bioavailability by manipulation of polarity at the P3 pyridine position (Z = H, piperidine; Z = O, pyridine-N-oxide).Figure optionsDownload as PowerPoint slide

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 21, Issue 5, 1 March 2011, Pages 1532–1535
نویسندگان
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