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

Research output: Contribution to journal › Article › peer-review

44 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
Externally published	Yes

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bmcl.2008.08.018

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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 et al.

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

Research output: Contribution to journal › Article › peer-review

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

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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",

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AU - Ogino, Yoshio

AU - Ohtake, Norikazu

AU - Nagae, Yoshikazu

AU - Matsuda, Kenji

AU - Moriya, Minoru

AU - Suga, Takuya

AU - Ishikawa, Makoto

AU - Kanesaka, Maki

AU - Mitobe, Yuko

AU - Ito, Junko

AU - Kanno, Tetsuya

AU - Ishihara, Akane

AU - Iwaasa, Hisashi

AU - Ohe, Tomoyuki

AU - Kanatani, Akio

AU - Fukami, Takehiro

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AB - 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

KW - Antagonist

KW - Anti-obesity

KW - Benzimidazole

KW - Neuropeptide Y

KW - Y5 receptor

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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