کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10584176 | 981326 | 2013 | 22 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Lead optimization of 5-amino-6-(2,2-dimethyl-5-oxo-4-phenylpiperazin-1-yl)-4-hydroxyhexanamides to reduce a cardiac safety issue: Discovery of DS-8108b, an orally active renin inhibitor
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کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
With the aim to address an undesired cardiac issue observed with our related compound in the recently disclosed novel series of renin inhibitors, further chemical modifications of this series were performed. Extensive structure-activity relationships studies as well as in vivo cardiac studies using the electrophysiology rat model led to the discovery of clinical candidate trans-adamantan-1-ol analogue 56 (DS-8108b) as a potent renin inhibitor with reduced potential cardiac risk. Oral administration of single doses of 3 and 10Â mg/kg of 56 in cynomolgus monkeys pre-treated with furosemide led to significant reduction of mean arterial blood pressure for more than 12Â h.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 21, Issue 11, 1 June 2013, Pages 3175-3196
Journal: Bioorganic & Medicinal Chemistry - Volume 21, Issue 11, 1 June 2013, Pages 3175-3196
نویسندگان
Yuji Nakamura, Teppei Fujimoto, Yasuyuki Ogawa, Hidenori Namiki, Sayaka Suzuki, Masayoshi Asano, Chie Sugita, Akiyoshi Mochizuki, Shojiro Miyazaki, Kazuhiko Tamaki, Yoko Nagai, Shin-ichi Inoue, Takahiro Nagayama, Mikio Kato, Katsuyoshi Chiba,