Synthesis and Characterization of Radioiodinated MD-230254 : A New Ligand for Potential Imaging of Monoamine Oxidase B Activity by Single Photon Emission Computed Tomography
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概要
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A series of iodinated analogues of MD-230254 was synthesized and evaluated for inhibitory potency and selectivity toward monoamine oxidase B (MAO-B). Among them, 5-[4-(2-iodobenzyloxy)phenyl]-3-(cyanoethyl)-1,3,4-oxadiazole-2(3H)one (2-IBPO) was found to have high inhibitory potency and selectivity toward MAO-B (IC_<50>= 2.0 n_M, MAO-A/MAO-B >50000). Analysis of the inhibition kinetics indicated that 2-IBPO acts in a two-step mechanism as a competitive, slow, and tight-binding inhibitor of MAO-B with a Ki value of 2.4 n_M and an overall Ki^* value at an equilibrium of 3.8 n_M. The new radioligand for MAO-B, [^<125>I]2-IBPO was conveniently synthesized from a tributylstannyl precursor by an iododestannylation reaction using sodium [^<125>I]iodide and hydrogen peroxide with high radiochemical yield. The in vivo tissue distribution studies of [^<125>I]2-IBPO demonstrated its high initial uptake and prolonged retention in the brain. A selective interaction of [^<125>I]2-IBPO with MAO-B was confirmed by the pretreatment experiment with well known MAO specific inhibitors, l-deprenyl, Ro-16-6491, clorgyline, and Ro-41-1049. These very desirable characteristics of [^<125>I]2-IBPO suggested that a ^<123>I-labeled counterpart, [^<123>I]2-IBPO, would have great potential in in vivo studies of MAO-B in the human brain with single photon emission computed tomography (SPECT).
- 公益社団法人日本薬学会の論文
- 2002-05-01
著者
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Kagawa S
Osaka University Of Pharmaceutical Sciences
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Hirata M
Osaka University Of Pharmaceutical Sciences
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Hirata Masahiko
Osaka University Of Pharmaceutical Sciences
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Yoshimoto M
Osaka University Of Pharmaceutical Sciences
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OHMOMO Yoshiro
Osaka University of Pharmaceutical Sciences
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KAGAWA Shinya
Osaka University of Pharmaceutical Sciences
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YOSHIMOTO Mitsuyoshi
Osaka University of Pharmaceutical Sciences
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Ohmomo Y
Osaka University Of Pharmaceutical Sciences
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