کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1372302 | 981868 | 2013 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Discovery and optimisation of 1-hydroxyimino-3,3-diphenylpropanes, a new class of orally active GPBAR1 (TGR5) agonists
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کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
پیش نمایش صفحه اول مقاله

چکیده انگلیسی
A series of non-steroidal GPBAR1 (TGR5) agonists was developed from a hit in a high-throughput screening campaign. Lead identification efforts produced biphenyl-4-carboxylic acid derivative (R)-22, which displayed a robust secretion of PYY after oral administration in a degree that can be correlated with the unbound plasma concentration. Further optimisation work focusing on reduction of the lipophilicity provided the 1-phenylpiperidine-4-carboxylic acid derivative (R)-29 (RO5527239), which showed an improved secretion of PYY and GLP-1, translating into a significant reduction of postprandial blood glucose excursion in an oral glucose tolerance test in DIO mice.
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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 23, Issue 16, 15 August 2013, Pages 4627–4632
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 23, Issue 16, 15 August 2013, Pages 4627–4632
نویسندگان
Henrietta Dehmlow, Rubén Alvarez Sánchez, Stephan Bachmann, Caterina Bissantz, Fritz Bliss, Karin Conde-Knape, Martin Graf, Rainer E. Martin, Ulrike Obst Sander, Susanne Raab, Hans G.F. Richter, Sabine Sewing, Urs Sprecher, Christoph Ullmer,