909781-64-2Relevant academic research and scientific papers
A novel class of cycloalkano[b]pyridines as potent and orally active opioid receptor-like 1 antagonists with minimal binding affinity to the hERG K + channel
Yoshizumi, Takashi,Takahashi, Hirobumi,Miyazoe, Hiroshi,Sugimoto, Yuichi,Tsujita, Tomohiro,Kato, Tetsuya,Ito, Hirokatsu,Kawamoto, Hiroshi,Hirayama, Mioko,Ichikawa, Daisuke,Azuma-Kanoh, Tomoko,Ozaki, Satoshi,Shibata, Yoshihiro,Tani, Takeshi,Chiba, Masato,Ishii, Yasuyuki,Okuda, Shoki,Tadano, Kiyoshi,Fukuroda, Takahiro,Okamoto, Osamu,Ohta, Hisashi
experimental part, p. 4021 - 4029 (2009/05/26)
A series of compounds based on 7-{[4-(2-methylphenyl)piperidin-1-yl]methyl} -6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridine-9-ol ((-)-8b), a potent and selective opioid receptor-like 1 (ORL1) antagonist, was prepared and evaluated using structure-activity relationship studies with the aim of removing its affinity to human ether-a-go-go related gene (hERG) K+ channel. From these studies, 101 was identified as an optimized structure with respect to ORL1 antagonist activity, and affinity to the hERG K+channel. Furthermore, 101 showed good in vivo antagonism with a wide therapeutic index in regards to adverse cardiovascular effects.
