Design, synthesis, and structure-activity relationships of indole-3-heterocycles as agonists of the CB1 receptor.
Design, synthesis, and structure-activity relationships of indole-3-heterocycles as agonists of the CB1 receptor.
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DOI：
10.1016/j.bmcl.2010.10.093
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发表时间：
2011
影响因子：
2.7
通讯作者：
Angus J. Morrison;Julia M. Adam;James Baker;Robert A. Campbell;J. Clark;J. Cottney;M. Deehan;Anna-Marie Easson;Ruth Fields;S. Francis;Fiona Jeremiah;Neil S. Keddie;T. Kiyoi;D. Mcarthur;K. Meyer;P. Ratcliffe;J. Schulz;G. Wishart;K. Yoshiizumi
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文献类型：
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作者：
Angus J. Morrison;Julia M. Adam;James Baker;Robert A. Campbell;J. Clark;J. Cottney;M. Deehan;Anna-Marie Easson;Ruth Fields;S. Francis;Fiona Jeremiah;Neil S. Keddie;T. Kiyoi;D. Mcarthur;K. Meyer;P. Ratcliffe;J. Schulz;G. Wishart;K. Yoshiizumi
新的吲哚-3-杂环的设计和合成，并发现是有效的CB 1受体激动剂。从微粒体不稳定的铅1开始，进行了取代哌嗪酰胺的生物电子等排体方法。发现这是改善体外和体内稳定性的良好策略。这导致发现24，其在小鼠甩尾试验中与导联1相比具有增加的作用持续时间。
Novel indole-3-heterocycles were designed and synthesized and found to be potent CB1 receptor agonists. Starting from a microsomally unstable lead 1, a bioisostere approach replacing a piperazine amide was undertaken. This was found to be a good strategy for improving stability both in vitro and in vivo. This led to the discovery of 24, which had an increased duration of action in the mouse tail flick test in comparison to the lead 1.