کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10596258 | 981900 | 2009 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Cyanoguanidine-based lactam derivatives as a novel class of orally bioavailable factor Xa inhibitors
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کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Cyanoguanidine-based lactam derivatives as a novel class of orally bioavailable factor Xa inhibitors Cyanoguanidine-based lactam derivatives as a novel class of orally bioavailable factor Xa inhibitors](/preview/png/10596258.png)
چکیده انگلیسی
The N,Nâ²-disubstituted cyanoguanidine is an excellent bioisostere of the thiourea and ketene aminal functional groups. We report the design and synthesis of a novel class of cyanoguanidine-based lactam derivatives as potent and orally active FXa inhibitors. The SAR studies led to the discovery of compound 4 (BMS-269223, Ki = 6.5 nM, EC2xPT = 32 μM) as a selective, orally bioavailable FXa inhibitor with an excellent in vitro liability profile, favorable pharmacokinetics and pharmacodynamics in animal models. The X-ray crystal structure of 4 bound in FXa is presented and key ligand-protein interactions are discussed.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 19, Issue 15, 1 August 2009, Pages 4034-4041
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 19, Issue 15, 1 August 2009, Pages 4034-4041
نویسندگان
Yan Shi, Jing Zhang, Mengxiao Shi, Stephen P. O'Connor, Sharon N. Bisaha, Chi Li, Doree Sitkoff, Andrew T. Pudzianowski, Saeho Chong, Herbert E. Klei, Kevin Kish, Joseph Jr., Eddie C.-K. Liu, Karen S. Hartl, Steve M. Seiler, Thomas E. Steinbacher,