Fotsch Christopher, Biddlecome Gloria, Biswas Kaustav, Chen Jian Jeff, D'Amico Derin C, Groneberg Robert D, Han Nianhe Bruce, Hsieh Feng-Yin, Kamassah Augustus, Kumar Gondi, Lester-Zeiner Dianna, Liu Qingyian, Mareska David A, Riahi Babak Bobby, Wang Yueh-Ju Judy, Yang Kevin, Zhan James, Zhu Joe, Johnson Eileen, Ng Gordon, Askew Benny C
Amgen Inc., Department of Chemistry Research and Development, One Amgen Center Drive, Thousand Oaks, CA 91360, USA.
Bioorg Med Chem Lett. 2006 Apr 15;16(8):2071-5. doi: 10.1016/j.bmcl.2006.01.069. Epub 2006 Feb 7.
The bradykinin 1 (B1) receptor is upregulated during times of inflammation and is important for maintaining inflamed and chronic pain states. Blocking this receptor has been shown to reverse and/or ameliorate pain and inflammation in animal models. In this report, we describe a new class of B1 receptor antagonists that contain the piperidine acetic acid tetralin core. A structure-activity relationship for these analogs is described in this paper. The most potent compounds from this class have IC50s<20 nM in a B1 receptor functional assay. One of these compounds, 13g, shows modest oral bioavailability in rats.
缓激肽1（B1）受体在炎症期间会上调，对于维持炎症和慢性疼痛状态很重要。在动物模型中，阻断该受体已被证明可逆转和/或改善疼痛和炎症。在本报告中，我们描述了一类新的含有哌啶乙酸四氢萘核心的B1受体拮抗剂。本文描述了这些类似物的构效关系。这类化合物中最有效的化合物在B1受体功能测定中的IC50<20 nM。其中一种化合物13g在大鼠中显示出适度的口服生物利用度。
