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

Research output: Contribution to journalArticle

39 Citations (Scopus)

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
Externally publishedYes

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Structure-Activity Relationship
Derivatives
Lead compounds
Crowns
Urea
Brain
neuropeptide Y5 receptor
benzimidazole

Keywords

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

ASJC Scopus subject areas

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

Cite this

Design, syntheses, and structure-activity relationships of novel NPY Y5 receptor antagonists : 2-{3-Oxospiro[isobenzofuran-1(3H),4′-piperidin]-1′-yl}benzimidazole derivatives. / Ogino, Yoshio; Ohtake, Norikazu; Nagae, Yoshikazu; Matsuda, Kenji; Moriya, Minoru; Suga, Takuya; Ishikawa, Makoto; Kanesaka, Maki; Mitobe, Yuko; Ito, Junko; Kanno, Tetsuya; Ishihara, Akane; Iwaasa, Hisashi; Ohe, Tomoyuki; Kanatani, Akio; Fukami, Takehiro.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 18, No. 18, 15.09.2008, p. 5010-5014.

Research output: Contribution to journalArticle

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, vol. 18, no. 18, pp. 5010-5014. https://doi.org/10.1016/j.bmcl.2008.08.018
Ogino, Yoshio ; Ohtake, Norikazu ; Nagae, Yoshikazu ; Matsuda, Kenji ; Moriya, Minoru ; Suga, Takuya ; Ishikawa, Makoto ; Kanesaka, Maki ; Mitobe, Yuko ; Ito, Junko ; Kanno, Tetsuya ; Ishihara, Akane ; Iwaasa, Hisashi ; Ohe, Tomoyuki ; Kanatani, Akio ; Fukami, Takehiro. / Design, syntheses, and structure-activity relationships of novel NPY Y5 receptor antagonists : 2-{3-Oxospiro[isobenzofuran-1(3H),4′-piperidin]-1′-yl}benzimidazole derivatives. In: Bioorganic and Medicinal Chemistry Letters. 2008 ; Vol. 18, No. 18. pp. 5010-5014.
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