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

doi:10.1016/j.bmcl.2008.08.018

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

School of Pharmaceutical Sciences

Research output: Contribution to journal › Article

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 language	English
Pages (from-to)	5010-5014
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	18
Issue number	18
DOIs	https://doi.org/10.1016/j.bmcl.2008.08.018
Publication status	Published - 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

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 journal › Article

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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AU - Ishikawa, Makoto

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AU - Mitobe, Yuko

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AU - Kanno, Tetsuya

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10.1016/j.bmcl.2008.08.018