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ID: ALA1144170

Journal: Bioorg Med Chem Lett

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.

Authors: 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.

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: IC(50)=3.3 nM) and 5-(2-methyltetrazol-5-yl)benzimidazole (2u: IC(50)=5.9 nM), both of which are potent, selective, and orally bioavailable Y5 receptor antagonists.

CiteXplore: 18752943

DOI: 10.1016/j.bmcl.2008.08.021