Design, syntheses, and structure-activity relationships of novel NPY Y5 receptor antagonists: 2-{3-Oxospiro[isobenzofuran-1(3H),4′-piperidin]-1′-yl}benzimidazole derivatives

Yoshio Ogino, Norikazu Ohtake, Yoshikazu Nagae, Kenji Matsuda, Minoru Moriya, Takuya Suga, Makoto Ishikawa, Maki Kanesaka, Yuko Mitobe, Junko Ito, Tetsuya Kanno, Akane Ishihara, Hisashi Iwaasa, Tomoyuki Ohe, Akio Kanatani, Takehiro Fukami

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Abstract

Design, syntheses, and structure-activity relationships of a novel class of 2-{3-oxospiro[isobenzofuran-1(3H),4′-piperidin]-1′-yl}benzimidazole NPY Y5 receptor antagonists are described. The benzimidazole structures were newly designed based on the urea linkage of our prototype Y5 receptor antagonists (2 and 3). By optimizing substituents on the benzimidazole core part of the lead compound 5a, we were able to develop a potent, orally available, and brain-penetrable Y5 selective antagonist (5k). Crown

Original languageEnglish
Pages (from-to)5010-5014
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume18
Issue number18
DOIs
Publication statusPublished - 2008 Sep 15

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Keywords

  • Antagonist
  • Anti-obesity
  • Benzimidazole
  • Neuropeptide Y
  • Y5 receptor

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

Ogino, Y., Ohtake, N., Nagae, Y., Matsuda, K., Moriya, M., Suga, T., Ishikawa, M., Kanesaka, M., Mitobe, Y., Ito, J., Kanno, T., Ishihara, A., Iwaasa, H., Ohe, T., Kanatani, A., & Fukami, T. (2008). Design, syntheses, and structure-activity relationships of novel NPY Y5 receptor antagonists: 2-{3-Oxospiro[isobenzofuran-1(3H),4′-piperidin]-1′-yl}benzimidazole derivatives. Bioorganic and Medicinal Chemistry Letters, 18(18), 5010-5014. https://doi.org/10.1016/j.bmcl.2008.08.018