Aryl urea derivatives of spiropiperidines as NPY Y5 receptor antagonists

Toshiyuki Takahashi, Yuji Haga, Toshihiro Sakamoto, Minoru Moriya, Osamu Okamoto, Katsumasa Nonoshita, Takunobu Shibata, Takuya Suga, Hirobumi Takahashi, Tomoko Hirohashi, Aya Sakuraba, Akira Gomori, Hisashi Iwaasa, Tomoyuki Ohe, Akane Ishihara, Yasuyuki Ishii, Akio Kanatani, Takehiro Fukami

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Continuing medicinal chemistry studies to identify spiropiperidine-derived NPY Y5 receptor antagonists are described. Aryl urea derivatives of a variety of spiropiperidines were tested for their NPY Y5 receptor binding affinities. Of the spiropiperidines so far examined, spiro[3-oxoisobenzofurane-1(3H),4′-piperidine] was a useful scaffold for producing orally active NPY Y5 receptor antagonists. Oral administration of 5c significantly inhibited the Y5 agonist-induced food intake in rats with a minimum effective dose of 3 mg/kg. In addition, this compound was efficacious in decreasing body weight in diet-induced obese mice.

Original languageEnglish
Pages (from-to)3511-3516
Number of pages6
JournalBioorganic and Medicinal Chemistry Letters
Volume19
Issue number13
DOIs
Publication statusPublished - 2009 Jul 1
Externally publishedYes

Fingerprint

Urea
Derivatives
Obese Mice
Pharmaceutical Chemistry
Nutrition
Scaffolds
Oral Administration
Rats
Eating
Body Weight
Diet
neuropeptide Y5 receptor
spiro(3-oxoisobenzofurane-1(3H),4'-piperidine)

Keywords

  • Antagonist
  • Neuropeptide Y
  • NPY
  • Obesity

ASJC Scopus subject areas

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

Cite this

Takahashi, T., Haga, Y., Sakamoto, T., Moriya, M., Okamoto, O., Nonoshita, K., ... Fukami, T. (2009). Aryl urea derivatives of spiropiperidines as NPY Y5 receptor antagonists. Bioorganic and Medicinal Chemistry Letters, 19(13), 3511-3516. https://doi.org/10.1016/j.bmcl.2009.05.013

Aryl urea derivatives of spiropiperidines as NPY Y5 receptor antagonists. / Takahashi, Toshiyuki; Haga, Yuji; Sakamoto, Toshihiro; Moriya, Minoru; Okamoto, Osamu; Nonoshita, Katsumasa; Shibata, Takunobu; Suga, Takuya; Takahashi, Hirobumi; Hirohashi, Tomoko; Sakuraba, Aya; Gomori, Akira; Iwaasa, Hisashi; Ohe, Tomoyuki; Ishihara, Akane; Ishii, Yasuyuki; Kanatani, Akio; Fukami, Takehiro.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 19, No. 13, 01.07.2009, p. 3511-3516.

Research output: Contribution to journalArticle

Takahashi, T, Haga, Y, Sakamoto, T, Moriya, M, Okamoto, O, Nonoshita, K, Shibata, T, Suga, T, Takahashi, H, Hirohashi, T, Sakuraba, A, Gomori, A, Iwaasa, H, Ohe, T, Ishihara, A, Ishii, Y, Kanatani, A & Fukami, T 2009, 'Aryl urea derivatives of spiropiperidines as NPY Y5 receptor antagonists', Bioorganic and Medicinal Chemistry Letters, vol. 19, no. 13, pp. 3511-3516. https://doi.org/10.1016/j.bmcl.2009.05.013
Takahashi T, Haga Y, Sakamoto T, Moriya M, Okamoto O, Nonoshita K et al. Aryl urea derivatives of spiropiperidines as NPY Y5 receptor antagonists. Bioorganic and Medicinal Chemistry Letters. 2009 Jul 1;19(13):3511-3516. https://doi.org/10.1016/j.bmcl.2009.05.013
Takahashi, Toshiyuki ; Haga, Yuji ; Sakamoto, Toshihiro ; Moriya, Minoru ; Okamoto, Osamu ; Nonoshita, Katsumasa ; Shibata, Takunobu ; Suga, Takuya ; Takahashi, Hirobumi ; Hirohashi, Tomoko ; Sakuraba, Aya ; Gomori, Akira ; Iwaasa, Hisashi ; Ohe, Tomoyuki ; Ishihara, Akane ; Ishii, Yasuyuki ; Kanatani, Akio ; Fukami, Takehiro. / Aryl urea derivatives of spiropiperidines as NPY Y5 receptor antagonists. In: Bioorganic and Medicinal Chemistry Letters. 2009 ; Vol. 19, No. 13. pp. 3511-3516.
@article{cbbc72f1beba44e785b334b1d8a7555c,
title = "Aryl urea derivatives of spiropiperidines as NPY Y5 receptor antagonists",
abstract = "Continuing medicinal chemistry studies to identify spiropiperidine-derived NPY Y5 receptor antagonists are described. Aryl urea derivatives of a variety of spiropiperidines were tested for their NPY Y5 receptor binding affinities. Of the spiropiperidines so far examined, spiro[3-oxoisobenzofurane-1(3H),4′-piperidine] was a useful scaffold for producing orally active NPY Y5 receptor antagonists. Oral administration of 5c significantly inhibited the Y5 agonist-induced food intake in rats with a minimum effective dose of 3 mg/kg. In addition, this compound was efficacious in decreasing body weight in diet-induced obese mice.",
keywords = "Antagonist, Neuropeptide Y, NPY, Obesity",
author = "Toshiyuki Takahashi and Yuji Haga and Toshihiro Sakamoto and Minoru Moriya and Osamu Okamoto and Katsumasa Nonoshita and Takunobu Shibata and Takuya Suga and Hirobumi Takahashi and Tomoko Hirohashi and Aya Sakuraba and Akira Gomori and Hisashi Iwaasa and Tomoyuki Ohe and Akane Ishihara and Yasuyuki Ishii and Akio Kanatani and Takehiro Fukami",
year = "2009",
month = "7",
day = "1",
doi = "10.1016/j.bmcl.2009.05.013",
language = "English",
volume = "19",
pages = "3511--3516",
journal = "Bioorganic and Medicinal Chemistry Letters",
issn = "0960-894X",
publisher = "Elsevier Limited",
number = "13",

}

TY - JOUR

T1 - Aryl urea derivatives of spiropiperidines as NPY Y5 receptor antagonists

AU - Takahashi, Toshiyuki

AU - Haga, Yuji

AU - Sakamoto, Toshihiro

AU - Moriya, Minoru

AU - Okamoto, Osamu

AU - Nonoshita, Katsumasa

AU - Shibata, Takunobu

AU - Suga, Takuya

AU - Takahashi, Hirobumi

AU - Hirohashi, Tomoko

AU - Sakuraba, Aya

AU - Gomori, Akira

AU - Iwaasa, Hisashi

AU - Ohe, Tomoyuki

AU - Ishihara, Akane

AU - Ishii, Yasuyuki

AU - Kanatani, Akio

AU - Fukami, Takehiro

PY - 2009/7/1

Y1 - 2009/7/1

N2 - Continuing medicinal chemistry studies to identify spiropiperidine-derived NPY Y5 receptor antagonists are described. Aryl urea derivatives of a variety of spiropiperidines were tested for their NPY Y5 receptor binding affinities. Of the spiropiperidines so far examined, spiro[3-oxoisobenzofurane-1(3H),4′-piperidine] was a useful scaffold for producing orally active NPY Y5 receptor antagonists. Oral administration of 5c significantly inhibited the Y5 agonist-induced food intake in rats with a minimum effective dose of 3 mg/kg. In addition, this compound was efficacious in decreasing body weight in diet-induced obese mice.

AB - Continuing medicinal chemistry studies to identify spiropiperidine-derived NPY Y5 receptor antagonists are described. Aryl urea derivatives of a variety of spiropiperidines were tested for their NPY Y5 receptor binding affinities. Of the spiropiperidines so far examined, spiro[3-oxoisobenzofurane-1(3H),4′-piperidine] was a useful scaffold for producing orally active NPY Y5 receptor antagonists. Oral administration of 5c significantly inhibited the Y5 agonist-induced food intake in rats with a minimum effective dose of 3 mg/kg. In addition, this compound was efficacious in decreasing body weight in diet-induced obese mice.

KW - Antagonist

KW - Neuropeptide Y

KW - NPY

KW - Obesity

UR - http://www.scopus.com/inward/record.url?scp=66349107638&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=66349107638&partnerID=8YFLogxK

U2 - 10.1016/j.bmcl.2009.05.013

DO - 10.1016/j.bmcl.2009.05.013

M3 - Article

VL - 19

SP - 3511

EP - 3516

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

SN - 0960-894X

IS - 13

ER -