Syntheses and structure-activity relationships of novel, potent, and selective trans-2-[3-oxospiro[isobenzofuran-1(3H),1′-cyclohexan]-4′-yl]benzimidazole NPY Y5 receptor antagonists

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

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Syntheses and structure-activity relationships of a novel class of 2-[3-oxospiro[isobenzofuran-1(3H),1′-cyclohexan]-4′-yl]benzimidazole NPY Y5 receptor antagonists are described. Optimization of the lead compound 2a by incorporating substituents into the 5-position or into both the 5- and 6-positions of the benzimidazole core part led to the identification of 5-(5-methyl-1,2,4-oxadiazol-2-yl)benzimidazole (2r: IC50 = 3.3 nM) and 5-(2-methyltetrazol-5-yl)benzimidazole (2u: IC50 = 5.9 nM), both of which are potent, selective, and orally bioavailable Y5 receptor antagonists. Crown

Original languageEnglish
Pages (from-to)4997-5001
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume18
Issue number18
DOIs
Publication statusPublished - 2008 Sep 15
Externally publishedYes

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

Fingerprint Dive into the research topics of 'Syntheses and structure-activity relationships of novel, potent, and selective trans-2-[3-oxospiro[isobenzofuran-1(3H),1′-cyclohexan]-4′-yl]benzimidazole NPY Y5 receptor antagonists'. Together they form a unique fingerprint.

  • Cite this

    Ogino, Y., Ohtake, N., Nagae, Y., Matsuda, K., Ishikawa, M., Moriya, M., Kanesaka, M., Mitobe, Y., Ito, J., Kanno, T., Ishihara, A., Iwaasa, H., Ohe, T., Kanatani, A., & Fukami, T. (2008). Syntheses and structure-activity relationships of novel, potent, and selective trans-2-[3-oxospiro[isobenzofuran-1(3H),1′-cyclohexan]-4′-yl]benzimidazole NPY Y5 receptor antagonists. Bioorganic and Medicinal Chemistry Letters, 18(18), 4997-5001. https://doi.org/10.1016/j.bmcl.2008.08.021