2. Academic Validation
  3. Discovery of novel chiral diazepines as bombesin receptor subtype-3 (BRS-3) agonists with low brain penetration

Discovery of novel chiral diazepines as bombesin receptor subtype-3 (BRS-3) agonists with low brain penetration

  • Bioorg Med Chem Lett. 2014 Feb 1;24(3):750-5. doi: 10.1016/j.bmcl.2013.12.106.
Tetsuyoshi Matsufuji 1,  Kousei Shimada 2,  Shozo Kobayashi 2,  Asuka Kawamura 2,  Teppei Fujimoto 2,  Tsuyoshi Arita 2,  Takashi Hara 3,  Masahiro Konishi 3,  Rie Abe-Ohya 3,  Masanori Izumi 3,  Yoshitaka Sogawa 3,  Youko Nagai 4,  Kazuhiro Yoshida 4,  Hisashi Takahashi 2
Affiliations

Affiliations

  • 1 Medicinal Chemistry Research Laboratories, Daiichi Sankyo Co., Ltd, 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan. Electronic address: [email protected].
  • 2 Medicinal Chemistry Research Laboratories, Daiichi Sankyo Co., Ltd, 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
  • 3 Cardiovascular Metabolics Research Laboratories, Daiichi Sankyo Co., Ltd, 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
  • 4 Drug Metabolism & Pharmacokinetics Research Laboratories, Daiichi Sankyo Co., Ltd, 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
PMID: 24412111 DOI: 10.1016/j.bmcl.2013.12.106
Abstract

The discovery and optimization of a novel series of BRS-3 agonists are described. We explored a potent BRS-3 agonist with low brain penetration to avoid an adverse effect derived from central nervous system exposure. Through the derivatization process, chiral diazepines 9f and 9g were identified as possessing low brain penetration as well as potent in vitro activity against human and mouse BRS-3s.

Keywords

Bombesin receptor subtype-3 (BRS-3) agonists; Brain penetration; Diazepine.

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