Kobayashi Kensuke, Uchiyama Minaho, Ito Hirokatsu, Takahashi Hirobumi, Yoshizumi Takashi, Sakoh Hiroki, Nagatomi Yasushi, Asai Masanori, Miyazoe Hiroshi, Tsujita Tomohiro, Hirayama Mioko, Ozaki Satoshi, Tani Takeshi, Ishii Yasuyuki, Ohta Hisashi, Okamoto Osamu
Tsukuba Research Institute, Banyu Pharmaceutical Co., Ltd, Okubo-3, Tsukuba, Ibaraki 300-2611, Japan.
Bioorg Med Chem Lett. 2009 Jul 1;19(13):3627-31. doi: 10.1016/j.bmcl.2009.04.116. Epub 2009 May 3.
The synthesis and biological evaluation of new potent opioid receptor-like 1 antagonists are presented. A structure-activity relationship (SAR) study of arylpyrazole lead compound 1 obtained from library screening identified compound 31, (1S,3R)-N-{[1-(3-chloropyridin-2-yl)-5-(5-fluoro-6-methylpyridin-3-yl)-4-methyl-1H-pyrazol-3-yl]methyl}-3-fluorocyclopentanamine, which exhibits high intrinsic potency and selectivity against other opioid receptors and hERG potassium channel.
本文介绍了新型强效阿片样物质受体-1拮抗剂的合成及生物学评价。对通过文库筛选获得的芳基吡唑先导化合物1进行的构效关系（SAR）研究确定了化合物31，即(1S,3R)-N-{[1-(3-氯吡啶-2-基)-5-(5-氟-6-甲基吡啶-3-基)-4-甲基-1H-吡唑-3-基]甲基}-3-氟环戊胺，该化合物对其他阿片受体和人醚-去极化激活的钾通道（hERG）表现出高内在活性和选择性。
