Investigation of piperazine benzamides as human β3 adrenergic receptor agonists for the treatment of overactive bladder
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- 作者：Bart H. Harper ; bart_harper@merck.com ; Liping Wang ; Cheng Zhu ; Nam F. Kar ; Bing Li ; Christopher R. Moyes ; Stephen D. Goble ; Melissa Costa ; Karen Dingley ; Jerry Di Salvo ; Sookhee N. Ha ; Amanda Hurley ; Xiaofang Li ; Randy R. Miller ; Hiroshi Nagabukuro ; Gino M. Salituro ; Sean Smith ; Mary Struthers ; Jeffrey J. Hale ; Scott D. Edmondson ; Richard Berger
- 关键词：β3-Adrenergic receptor agonist ; Reverse amide ; Pyrrolidine scaffold ; Overactive bladder ; Norepinephrine transporter
- 刊名：Bioorganic & Medicinal Chemistry Letters
- 出版年：2017
- 出版时间：15 February 2017
- 年：2017
- 卷：27
- 期：4
- 页码：1094-1098
- 全文大小：442 K
- 卷排序：27
文摘
The synthesis of a novel class of piperazine benzamide (reverse amides) targeting the human β3-adrenergic receptor for the treatment of overactive bladder (OAB) is described. The SAR studies directed towards maintaining well established β3 potency and selectivities while improving the overall pharmacokinetic profile in the reverse amide class will be evaluated. The results and consequences associated with functional activity at the norepinephrine transporter (NET) will also be discussed.