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

doi:10.1016/j.bmcl.2009.05.013

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 journal › Article › peer-review

16 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 language	English
Pages (from-to)	3511-3516
Number of pages	6
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	19
Issue number	13
DOIs	https://doi.org/10.1016/j.bmcl.2009.05.013
Publication status	Published - 2009 Jul 1
Externally published	Yes

Keywords

Antagonist
NPY
Neuropeptide Y
Obesity

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.2009.05.013

Cite this

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, 19(13), 3511-3516. https://doi.org/10.1016/j.bmcl.2009.05.013

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

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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.",

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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

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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 - NPY

KW - Neuropeptide Y

KW - Obesity

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Aryl urea derivatives of spiropiperidines as NPY Y5 receptor antagonists

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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