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 language | English |
|---|---|
| Pages (from-to) | 4997-5001 |
| Number of pages | 5 |
| Journal | Bioorganic and Medicinal Chemistry Letters |
| Volume | 18 |
| Issue number | 18 |
| DOIs | |
| Publication status | Published - 2008 Sep 15 |
| Externally published | Yes |
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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
}
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
C2 - 18752943
AN - SCOPUS:51349130429
VL - 18
SP - 4997
EP - 5001
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
SN - 0960-894X
IS - 18
ER -