Penta-substituted benzimidazoles as potent antagonists of the calcium-sensing receptor (CaSR-antagonists)

被引:9
作者
Gerspacher, Marc [1 ]
Altmann, Eva [1 ]
Beerli, Rene [1 ]
Buhl, Thomas [1 ]
Endres, Ralf [1 ]
Gamse, Rainer [1 ]
Kameni-Tcheudji, Jacques [1 ]
Kneissel, Michaela [1 ]
Krawinkler, Karl Heinz [1 ]
Missbach, Martin [1 ]
Schmidt, Alfred [1 ]
Seuwen, Klaus [1 ]
Weiler, Sven [1 ]
Widler, Leo [1 ]
机构
[1] Novartis Pharma AG, Novartis Inst BioMed Res, CH-4002 Basel, Switzerland
关键词
Calcium-sensing receptor (CaSR); Parathyroid hormone (PTH); Bone formation; Osteoporosis; CaSR-antagonist; Benzimidazoles; BONE;
D O I
10.1016/j.bmcl.2010.07.016
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
A series of novel benzimidazole derivatives has been designed via a scaffold morphing approach based on known calcilytics chemotypes. Subsequent lead optimisation led to the discovery of penta-substituted benzimidazoles that exhibit attractive in vitro and in vivo calcium-sensing receptor (CaSR) inhibitory profiles. In addition, synthesis and structure-activity relationship data are provided. (C) 2010 Elsevier Ltd. All rights reserved.
引用
收藏
页码:5161 / 5164
页数:4
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