2. Academic Validation
  3. Discovery of novel PTHR1 antagonists: Design, synthesis, and structure activity relationships

Discovery of novel PTHR1 antagonists: Design, synthesis, and structure activity relationships

  • Bioorg Med Chem Lett. 2019 Sep 15;29(18):2613-2616. doi: 10.1016/j.bmcl.2019.07.052.
Yoshikazu Arai 1,  Yohei Kiyotsuka 2,  Kousei Shimada 2,  Kazunori Oyama 3,  Masanori Izumi 3
Affiliations

Affiliations

  • 1 Medicinal Chemistry Research Laboratories, Daiichi Sankyo Co, Ltd, 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan. Electronic address: arai.yoshikazu.mh@daiichisankyo.co.jp.
  • 2 Medicinal Chemistry Research Laboratories, Daiichi Sankyo Co, Ltd, 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
  • 3 Cardiovascular Metabolic Research Laboratories, Daiichi Sankyo Co, Ltd, 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
PMID: 31383587 DOI: 10.1016/j.bmcl.2019.07.052
Abstract

The discovery and optimization of a novel series of PTHR1 antagonists are described. Starting from known PTHR1 antagonists, we identified more potent 1,4-benzodiazepin-2-one derivatives by means of a scaffold-hopping approach. The representative compound 23 (DS08210767) exhibited nanomolar-level PTHR1 antagonist activity and potential oral bioavailability in a pharmacokinetic study.

Keywords

1,4-Benzodiazepin-2-one; PTH type 1 receptor (PTHR1) antagonist; Parathyroid hormone (PTH); Scaffold hopping.

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