Studies on Novel Bone Resorption Inhibitors. II. Synthesis and Pharmacological Activities of Fused Aza-heteroarylbisphosphonate Derivatives

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概要

• 論文の詳細を見る

• Two new series of fused aza-heteroarylbisphosphonates (5,8), which are structurally quite different from incadronate (YM175), and related compounds were synthesized and evaluated for antiresorptive activity using a parathyroid hormone (PTH)-induced hypercalcemia model in rats (PIH model). Among these compounds, several exhibited more potent antiresorptive activity than pamidronate. In particular, [1-hydroxy-2-(imidazo[1,2-α]pyridin-3-yl)ethylidene]bisphosphonic acid (5b, minodronate) was 100-fold more potent than pamidronate in not only the PIH model, but also in an immobilization bone atrophy model in rats (DA model), and was selected for clinical development. The structure-activity relationships in these new series of bisphosphonates are discussed.

• 公益社団法人日本薬学会の論文
• 1998-11-15

著者

• Takeuchi M

  Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co. Ltd.

• Takeuchi Makoto

  Chemistry Research Laboratories Astellas Pharmaceutical Inc.

• KURIHARA Hiroyuki

  Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.,

• TAKEUCHI Makoto

  Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.,

• ISOMURA Yasuo

  Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.,

• Takeuchi M

  Chemistry Research Laboratories Astellas Pharmaceutical Inc.

• Isomura Y

  Yamanouchi Pharmaceutical Co. Ltd. Ibaraki Jpn

• Kurihara H

  Graduate School Of Pharmaceutical Sciences Chiba University

• SAKAMOTO Shunichi

  Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.,

• KAWAMUKI Kousei

  Clinical Development Division, Yamanouchi Pharmaceutical Co., Ltd.,

• NAKAHARA Hideaki

  Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.,

• Kawamuki Kousei

  Clinical Development Division Yamanouchi Pharmaceutical Co. Ltd.

• Kubota H

  Chemistry Research Laboratories Astellas Pharmaceutical Inc.

• Nakahara H

  Graduate School Of Science And Engineering Saitama University

• Kurihara H

  Chemistry Research Laboratories Astellas Pharmaceutical Inc.

• Nakahara Hideaki

  Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co. Ltd.

• Sakamoto Shunichi

  Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co. Ltd.

• SAKAMOTO Shuichi

  Institute of Microbial Chemistry

• Sakamoto Shuichi

  Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.,

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