کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1372520 | 981871 | 2011 | 4 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Discovery of PF-184563, a potent and selective V1a antagonist for the treatment of dysmenorrhoea. The influence of compound flexibility on microsomal stability
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موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
The V1a receptor has emerged as an attractive target for a range of indications including Raynaud’s disease and dysmenorrhoea. As part of an effort to discover a new class of orally active V1a antagonist, we optimised a highly lipophilic, metabolically unstable lead into a range of potent, selective and metabolically stable V1a antagonists. In this communication, we demonstrate the series-dependent effect of limiting the number of rotatable bonds in order to decrease Cytochrome P450-mediated metabolism. This effort culminated in the discovery of PF-184563, a novel, selective V1a antagonist with excellent in vitro and in vivo properties.
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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 21, Issue 19, 1 October 2011, Pages 5684–5687
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 21, Issue 19, 1 October 2011, Pages 5684–5687
نویسندگان
Patrick S. Johnson, Thomas Ryckmans, Justin Bryans, Dave M. Beal, Kevin N. Dack, Neil Feeder, Anthony Harrison, Mark Lewis, Helen J. Mason, James Mills, Julie Newman, Christelle Pasquinet, Dave J. Rawson, Lee R. Roberts, Rachel Russell, Deborah Spark,