- Synthesis and characterization of novel radiofluorinated probes for positron emission tomography imaging of monoamine oxidase B
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Monoamine oxidase B (MAO-B), predominantly expressed in glial cells, plays an important role in neurotransmitter regulation, and MAO-B activity relates to several neuronal diseases. Here, we aimed to develop a radiofluorinated MAO-B imaging probe based on the structure of a selective MAO-B inhibitor, MD-230254. We synthesized and evaluated a series of compounds in vitro and in vivo. A series of fluorinated analogs of MD-230254 were synthesized and evaluated for inhibitory potency and selectivity toward MAO-B. 5-[4-(2-[18F]Fluorobenzyloxy)phenyl]-3-(2-cyanoethyl)-1,3,4-oxadiazol-2(3H)-one (2-[18F]FBPO) was synthesized from a corresponding tributylstannyl precursor and [18F]CH3COOF. Biodistribution after intravenous injection of 2-[18F]FBPO was evaluated in male ddY mice with or without pretreatment by inhibitors. Among the compounds synthesized and evaluated, 2-FBPO showed high inhibitory potency and selectivity toward MAO-B comparable with MD-230254. 2-[18F]FBPO was successfully synthesized by an electrophilic reaction with a high radiochemical purity of more than 99%. 2-[18F]FBPO was efficiently taken up by the brain and showed rapid blood clearance, which provided a brain/blood radioactivity ratio of 3.7 at 90 minutes postinjection. The brain radioactivity was significantly decreased by pretreatment with an MAO-B selective inhibitor. The great potential of 2-[18F]FBPO as an MAO-B imaging probe, applicable to a variety of diseases, is indicated.
- Yoshimoto, Mitsuyoshi,Hirata, Masahiko,Kagawa, Shinya,Magata, Yasuhiro,Ohmomo, Yoshiro,Temma, Takashi
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p. 580 - 587
(2019/08/01)
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- Synthesis and anticonvulsant activity evaluation of 4-butyl-5-(4- alkoxyphenyl)-2H-1,2,4-triazole-3(4H)-ones
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A series of 4-butyl-5-(4-alkoxyphenyl)-2H-1,2,4-triazole-3(4H)-ones (6a-6u) was designed and synthesized. The anticonvulsant effects and neurotoxicity of the compounds were evaluated with maximal electroshock test and rotarod test. Among the synthetic compounds, 4-butyl-5-(4-(2-fluorinebenzyl)phenyl)-2H-1,2,4- triazole-3 (4H)-one (6k) was the most potent with ED50 value of 27.4 mg/kg and protective index (PI = TD50/ED50) value of 12.0. Besides the anti-MES efficacy, the potency of compound 6k against seizures induced by pentylenetetrazole (PTZ), 3-mercaptopropionic acid (3-MP), and bicuculline (BIC) was also established, which suggested that the mechanisms of action including enhancing of GABAergic activity might be involved in its anticonvulsant activity.
- Zhu, Zi-Shi,Wang, Shi-Ben,Deng, Xian-Qing,Liu, Da-Chuan,Quan, Zhe-Shan
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p. 628 - 635
(2014/05/20)
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- Hypolipidemic analogues of ethyl 4 benzyloxybenzoate
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A series of compounds related to ethyl 4-benzyloxybenzoate was synthesized and evaluated for potential hypolipidemic activity in rats. Structure-activity relationships are discussed in terms of cholesterol-lowering activity together with effects on body weight gain and liver lipids. A number of the compounds inhibited cholesterol and free fatty acid biosynthesis from [1-14C]acetate in rat liver slices in vitro. Ethyl 4-benzyloxybenzoate, ethyl 4-benzyloxybenzoic acid, ethyl 4-p-bromobenzyloxybenzoate, and ethyl 4-o-methoxybenzyloxyphenyl acetate exhibited the most favorable spectrum of activity.
- Baggaley,Fears,Hindley,Morgan,Murrell,Thorne
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p. 1388 - 1393
(2007/10/05)
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- Phenyl alkyleneoxy phenyl alkanoic acid esters
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Pharmaceutical compositions having hypolipidaemic and/or hypoglycaemic activity, contain a substituted (4-carboxyphenoxy) phenyl alkane derivative.
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