کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1362168 | 981480 | 2011 | 5 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Optimisation of 6-substituted isoquinolin-1-amine based ROCK-I 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: Optimisation of 6-substituted isoquinolin-1-amine based ROCK-I inhibitors Optimisation of 6-substituted isoquinolin-1-amine based ROCK-I inhibitors](/preview/png/1362168.png)
چکیده انگلیسی
Rho kinase is an important target implicated in a variety of cardiovascular diseases. Herein, we report the optimisation of the fragment derived ATP-competitive ROCK inhibitors 1 and 2 into lead compound 14A. The initial goal of improving ROCK-I potency relative to 1, whilst maintaining a good PK profile, was achieved through removal of the aminoisoquinoline basic centre. Lead 14A was equipotent against both ROCK-I and ROCK-II, showed good in vivo efficacy in the spontaneous hypertensive rat model, and was further optimised to demonstrate the scope for improving selectivity over PKA versus hydroxy Fasudil 3.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 21, Issue 4, 15 February 2011, Pages 1084-1088
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 21, Issue 4, 15 February 2011, Pages 1084-1088
نویسندگان
Peter Ray, Jane Wright, Julia Adam, Sylviane Boucharens, Darcey Black, Angus R. Brown, Ola Epemolu, Dan Fletcher, Margaret Huggett, Phil Jones, Steven Laats, Amanda Lyons, Jos de Man, Richard Morphy, Brad Sherborne, Lorcan Sherry, Nicole van Straten,