Discovery of evocalcet, a next-generation calcium-sensing receptor agonist for the treatment of hyperparathyroidism.

Hiroshi Miyazaki, Yousuke Ikeda, Osamu Sakurai, Tsutomu Miyake,Rie Tsubota,Jyunko Okabe,Masataka Kuroda, Yutaka Hisada,Tetsuya Yanagida,Hikaru Yoneda,Yukihito Tsukumo,Shin Tokunaga,Takehisa Kawata,Rikiya Ohashi,Hajime Fukuda,Koki Kojima,Ayako Kannami, Takayuki Kifuji,Naoya Sato, Akiko Idei,Taku Iguchi,Tetsuya Sakairi, Yasunori Moritani

Bioorganic & Medicinal Chemistry Letters（2018）

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摘要

•Optimization from cinacalcet resulted in the discovery of evocalcet.•CYP2D6 inhibition observed in cinacalcet is completely solved in evocalcet.•Gastrointestinal tract symptoms of cinacalcet are drastically improved in evocalcet.•Evocalcet will provide a novel therapeutic option for secondary hyperparathyroidism.

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关键词

Evocalcet,Calcium-sensing receptor (CaSR),Allosteric calcium-sensing receptor agonist,Hyperparathyroidism,Cinacalcet

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