کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1372164 | 981866 | 2011 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Discovery and optimization of indoles and 7-azaindoles as Rho kinase (ROCK) inhibitors (part-I)
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Rho kinase (ROCK) inhibitors are potential therapeutic agents to treat disorders such as hypertension, multiple sclerosis, cancers, and glaucoma. Here, we disclose the synthesis, optimization, biological evaluation of potent indole and 7-azaindole based ROCK inhibitors that have high potency on ROCK (IC50 = 1 nM) with 740-fold selectivity over PKA (47). Moreover, 47 showed very good DMPK properties making it a good candidate for further development. Finally, docking studies with a homology model of ROCK-II were performed to rationalize the binding mode of these compounds and showed the compounds bound in both orientations to take advantage to H-bonds with Lys-121 of ROCK-II.
Figure optionsDownload as PowerPoint slide
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 21, Issue 23, 1 December 2011, Pages 7107–7112
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 21, Issue 23, 1 December 2011, Pages 7107–7112
نویسندگان
Sarwat Chowdhury, E. Hampton Sessions, Jennifer R. Pocas, Wayne Grant, Thomas Schröter, Li Lin, Claudia Ruiz, Michael D. Cameron, Stephan Schürer, Philip LoGrasso, Thomas D. Bannister, Yangbo Feng,