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

研究成果: Article

14 引用 (Scopus)

抄録

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

元の言語English
ページ（範囲）4997-5001
ページ数5
ジャーナルBioorganic and Medicinal Chemistry Letters
巻18
発行部数18
DOI
出版物ステータスPublished - 2008 9 15
外部発表Yes

Fingerprint

Structure-Activity Relationship
Inhibitory Concentration 50
Lead compounds
Crowns
neuropeptide Y5 receptor
benzimidazole

ASJC Scopus subject areas

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

これを引用

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

：: Bioorganic and Medicinal Chemistry Letters, 巻 18, 番号 18, 15.09.2008, p. 4997-5001.

研究成果: Article

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, 巻. 18, 番号 18, pp. 4997-5001. https://doi.org/10.1016/j.bmcl.2008.08.021
Ogino Y, Ohtake N, Nagae Y, Matsuda K, Ishikawa M, Moriya M その他. 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. 2008 9 15;18(18):4997-5001. https://doi.org/10.1016/j.bmcl.2008.08.021
Ogino, Yoshio ; Ohtake, Norikazu ; Nagae, Yoshikazu ; Matsuda, Kenji ; Ishikawa, Makoto ; Moriya, Minoru ; Kanesaka, Maki ; Mitobe, Yuko ; Ito, Junko ; Kanno, Tetsuya ; Ishihara, Akane ; Iwaasa, Hisashi ; Ohe, Tomoyuki ; Kanatani, Akio ; Fukami, Takehiro. / 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. 2008 ; 巻 18, 番号 18. pp. 4997-5001.
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AU - Ogino, Yoshio

AU - Ohtake, Norikazu

AU - Nagae, Yoshikazu

AU - Matsuda, Kenji

AU - Ishikawa, Makoto

AU - Moriya, Minoru

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

PY - 2008/9/15

Y1 - 2008/9/15

N2 - 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

AB - 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

KW - Antagonist

KW - Anti-obesity

KW - Benzimidazole

KW - Neuropeptide Y

KW - Y5 receptor

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