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 journal › Article

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

Fingerprint

Structure-Activity Relationship
Inhibitory Concentration 50
Lead compounds
Crowns
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

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.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 18, No. 18, 15.09.2008, p. 4997-5001.

Research output: Contribution to journal › 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, vol. 18, no. 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 et al. 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 Sep 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. In: Bioorganic and Medicinal Chemistry Letters. 2008 ; Vol. 18, No. 18. pp. 4997-5001.
@article{175cad71526a40b682ee44f724ea83ba,
title = "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",
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",
keywords = "Antagonist, Anti-obesity, Benzimidazole, Neuropeptide Y, Y5 receptor",
author = "Yoshio Ogino and Norikazu Ohtake and Yoshikazu Nagae and Kenji Matsuda and Makoto Ishikawa and Minoru Moriya and Maki Kanesaka and Yuko Mitobe and Junko Ito and Tetsuya Kanno and Akane Ishihara and Hisashi Iwaasa and Tomoyuki Ohe and Akio Kanatani and Takehiro Fukami",
year = "2008",
month = "9",
day = "15",
doi = "10.1016/j.bmcl.2008.08.021",
language = "English",
volume = "18",
pages = "4997--5001",
journal = "Bioorganic and Medicinal Chemistry Letters",
issn = "0960-894X",
publisher = "Elsevier Limited",
number = "18",

}

TY - JOUR

T1 - 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

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

UR - http://www.scopus.com/inward/record.url?scp=51349130429&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=51349130429&partnerID=8YFLogxK

U2 - 10.1016/j.bmcl.2008.08.021

DO - 10.1016/j.bmcl.2008.08.021

M3 - Article

VL - 18

SP - 4997

EP - 5001

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

SN - 0960-894X

IS - 18

ER -

Access to Document