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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Abstract

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(3<i>H</i>)one (2-IBPO) was found to have high inhibitory potency and selectivity toward MAO-B (IC<sub>50</sub>=2.0 n<small>M</small>, 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 <i>Ki</i> value of 2.4 n<small>M</small> and an overall <i>Ki</i>* value at an equilibrium of 3.8 n<small>M</small>. The new radioligand for MAO-B, [<sup>125</sup>I]2-IBPO was conveniently synthesized from a tributylstannyl precursor by an iododestannylation reaction using sodium [<sup>125</sup>I]iodide and hydrogen peroxide with high radiochemical yield. The <i>in vivo</i> tissue distribution studies of [<sup>125</sup>I]2-IBPO demonstrated its high initial uptake and prolonged retention in the brain. A selective interaction of [<sup>125</sup>I]2-IBPO with MAO-B was confirmed by the pretreatment experiment with well known MAO specific inhibitors, <i>l</i>-deprenyl, Ro-16-6491, clorgyline, and Ro-41-1049. These very desirable characteristics of [<sup>125</sup>I]2-IBPO suggested that a <sup>123</sup>I-labeled counterpart, [<sup>123</sup>I]2-IBPO, would have great potential in <i>in vivo</i> studies of MAO-B in the human brain with single photon emission computed tomography (SPECT).

Journal

  • Chemical and Pharmaceutical Bulletin

    Chemical and Pharmaceutical Bulletin 50(5), 609-614, 2002-05-01

    The Pharmaceutical Society of Japan

References:  31

Codes

  • NII Article ID (NAID)
    110003616210
  • NII NACSIS-CAT ID (NCID)
    AA00602100
  • Text Lang
    ENG
  • Article Type
    ART
  • ISSN
    00092363
  • NDL Article ID
    6154934
  • NDL Source Classification
    ZS51(科学技術--薬学) // ZP1(科学技術--化学・化学工業)
  • NDL Call No.
    Z53-D167
  • Data Source
    CJP  NDL  NII-ELS  J-STAGE 
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