- Design, syntheses, and structure-activity relationships of novel NPY Y5 receptor antagonists: 2-{3-Oxospiro[isobenzofuran-1(3H),4′-piperidin]-1′-yl}benzimidazole derivatives
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Design, syntheses, and structure-activity relationships of a novel class of 2-{3-oxospiro[isobenzofuran-1(3H),4′-piperidin]-1′-yl}benzimidazole NPY Y5 receptor antagonists are described. The benzimidazole structures were newly designed based on the urea linkage of our prototype Y5 receptor antagonists (2 and 3). By optimizing substituents on the benzimidazole core part of the lead compound 5a, we were able to develop a potent, orally available, and brain-penetrable Y5 selective antagonist (5k). Crown Copyright
- Ogino, Yoshio,Ohtake, Norikazu,Nagae, Yoshikazu,Matsuda, Kenji,Moriya, Minoru,Suga, Takuya,Ishikawa, Makoto,Kanesaka, Maki,Mitobe, Yuko,Ito, Junko,Kanno, Tetsuya,Ishihara, Akane,Iwaasa, Hisashi,Ohe, Tomoyuki,Kanatani, Akio,Fukami, Takehiro
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scheme or table
p. 5010 - 5014
(2009/05/07)
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- Efficient synthesis of a highly selective NPY-5 receptor antagonist: A drug candidate for the treatment of obesity
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A concise and practical synthesis of highly selective NPY-5 receptor antagonist 1 is described. The animopyrazine intermediate 3 was synthesized via either monobromination of aminopyrazine or palladium-catalyzed regioselective debromination of dibromopyrazine followed by an efficient Suzuki-Miyaura coupling. For the preparation of the spirolactone piperidine 2, significantly improved yield was achieved by using a combination of n-BuMgCl and n-BuLi. This protocol also dramatically increased the thermal stability of the aryllithium intermediate and eliminated the requirement for costly cryogenic conditions. The union of the spirolactone piperidine 2 and aminopyrazine 3 via a carbonyl group was accomplished using phenyl chloroformate delivering the target molecule in high yield.
- Itoh, Takahiro,Kato, Shinji,Nonoyama, Nobuaki,Wada, Toshihiro,Maeda, Kenji,Mase, Toshiaki,Zhao, Matthew M.,Song, Jake Z.,Tschaen, David M.,McNamara, James M.
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p. 822 - 828
(2012/12/22)
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- MODULATORS OF MUSCARINIC RECEPTORS
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The present invention relates to modulators of muscarinic receptors. The present invention also provides compositions comprising such modulators, and methods therewith for treating muscarinic receptor mediated diseases.
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Page/Page column 71-72
(2010/11/08)
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