Novel benzofuran derivatives for PET imaging of beta-amyloid plaques in Alzheimer's disease brains

Journal of Medicinal Chemistry
Masahiro OnoMorio Nakayama

Abstract

A novel series of benzofuran derivatives as potential positron emission tomography (PET) tracers targeting amyloid plaques in Alzheimer's disease (AD) were synthesized and evaluated. The syntheses of benzofurans were successfully achieved by an intramolecular Wittig reaction between triphenylphosphonium salt and 4-nitrobenzoyl chloride. When in vitro binding studies using AD brain gray matter homogenates were carried out with a series of benzofuran derivatives, all the derivatives examined displayed high binding affinities with K(i) values in the subnanomolar range. Among these benzofuran derivatives, compound 8, 5-hydroxy-2-(4-methyaminophenyl)benzofuran, showed the lowest K(i) value (0.7 nM). In vitro fluorescent labeling of AD sections with compound 8 intensely stained not only amyloid plaques, but also neurofibrillary tangles. The (11)C labeled compound 8, [(11)C]8, was prepared by reacting the normethyl precursor, 5-hydroxy-2-(4-aminophenyl)benzofuran, with [(11)C]methyl triflate. The [(11)C]8 displayed moderate lipophilicity (log P = 2.36), very good brain penetration (4.8%ID/g at 2 min after iv injection in mice), and rapid washout from normal brains (0.4 and 0.2%ID/g at 30 and 60 min, respectively). In addition, this PE...Continue Reading

References

Nov 1, 1992·International Journal of Radiation Applications and Instrumentation. Part A, Applied Radiation and Isotopes·D M Jewett
Sep 1, 1980·Analytical Biochemistry·P J Munson, D Rodbard
Mar 11, 1999·Annals of Neurology·J L Price, J C Morris
Jul 6, 2000·International Journal of Pharmaceutics·M FeherJ M Schmidt
Aug 10, 2000·Nature Biotechnology·D J Selkoe
Aug 19, 2000·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·S D StyrenW E Klunk
Feb 24, 2001·Applied Radiation and Isotopes : Including Data, Instrumentation and Methods for Use in Agriculture, Industry and Medicine·A A WilsonS Houle
Mar 29, 2001·Physiological Reviews·D J Selkoe
Jun 13, 2003·Journal of Medicinal Chemistry·Chester A MathisWilliam E Klunk
Mar 3, 2004·Annals of Neurology·William E KlunkBengt Långström
May 12, 2004·Current Pharmaceutical Design·C A MathisW E Klunk
Aug 25, 2004·Lancet Neurology·Agneta Nordberg
Jun 10, 2005·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Julie C PriceChester A Mathis

❮ Previous
Next ❯

Citations

Mar 14, 2007·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Robert M Cohen
Aug 2, 2011·Chemical & Pharmaceutical Bulletin·Zhong-Zhen ZhouShu-Wen Liu
Mar 3, 2009·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Masahiro Ono
Jun 15, 2013·Beilstein Journal of Organic Chemistry·Todd J EckroatSylvie Garneau-Tsodikova
Jun 27, 2015·ACS Chemical Neuroscience·Patrick L DonabedianEva Y Chi
May 26, 2016·The Journal of Organic Chemistry·Yilong ZhaoJingping Qu
Feb 24, 2015·European Journal of Medicinal Chemistry·Ashish Radadiya, Anamik Shah
Aug 21, 2007·Chembiochem : a European Journal of Chemical Biology·Qian LiYoung-Tae Chang
Nov 11, 2017·Alzheimer's & Dementia : Translational Research & Clinical Interventions·Ying-Hwey NaiHiroshi Watabe
Aug 12, 2009·Molecular BioSystems·Tsuyoshi TakahashiHisakazu Mihara
Feb 26, 2019·Future Medicinal Chemistry·Caterina VicidominiGiovanni N Roviello
Apr 5, 2011·Chemical Biology & Drug Design·Ashley A Reinke, Jason E Gestwicki
Jan 3, 2014·Organic & Biomolecular Chemistry·Ashabha I LansakaraF Christopher Pigge
Oct 26, 2007·The Journal of Organic Chemistry·Zhiqiang LiangRuren Xu
Nov 11, 2010·ACS Medicinal Chemistry Letters·Masahiro OnoMorio Nakayama
Oct 12, 2010·The Journal of Organic Chemistry·Selvanathan Arumugam, Vladimir V Popik
Aug 28, 2020·Molecular Pharmaceutics·Jianhua JiaMengchao Cui
Mar 16, 2019·ACS Infectious Diseases·Takeshi FuchigamiMorio Nakayama

❮ Previous
Next ❯

Related Concepts

Related Feeds

Alzheimer's Disease: Neuroimaging

Neuroimaging can help identify pathological hallmarks of Alzheimer's disease (AD). Here is the latest research on neuroimaging modalities, including magnetic resonance imaging and positron emission tomography, in AD.

Alzheimer's Disease: Animal Models

Alzheimer's disease is a neurodegenerative disease which can be studied using various experimental systems. This feed focuses on animal models used for Alzheimer's disease research.

Alzheimer's Disease: Amyloid Beta

Alzheimer's disease is a neurodegenerative disease associated with the accumulation of amyloid plaques in the brain; these plaques are comprised of amyloid beta deposits. Here is the latest research in this field.