کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10596433 | 981902 | 2012 | 5 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Discovery, oral pharmacokinetics and in vivo efficacy of velusetrag, a highly selective 5-HT4 receptor agonist that has achieved proof-of-concept in patients with chronic idiopathic constipation
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کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Utilization of Theravance's multivalent approach to drug discovery towards 5-HT4 receptor agonists with a focus on identification of neutral (non-charged at physiological pH) secondary binding groups is described. Optimization of a quinolone-tropane primary binding group with a chiral 2-propanol linker to a range of neutral secondary binding group motifs, for binding affinity and functional potency at the 5-HT4 receptor, selectivity over the 5-HT3 receptor, oral pharmacokinetics, and in vivo efficacy in models of GI motility, afforded velusetrag (TD-5108). Velusetrag has achieved proof-of-concept in patients with chronic idiopathic constipation.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 22, Issue 19, 1 October 2012, Pages 6048-6052
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 22, Issue 19, 1 October 2012, Pages 6048-6052
نویسندگان
Daniel D. Long, Scott R. Armstrong, David T. Beattie, Seok-Ki Choi, Paul R. Fatheree, Roland A.L. Gendron, Daniel Genov, Adam A. Goldblum, Patrick P. Humphrey, Lan Jiang, Daniel G. Marquess, Jeng-Pyng Shaw, Jacqueline A.M. Smith, S. Derek Turner,