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@PHDTHESIS{Hocke:44139,
      author       = {Hocke, Carsten},
      title        = {{U}ntersuchungen zur n.c.a. 18{F}- und 123{I}-{M}arkierung
                      {S}ubtyp-selektiver {D}erivate des 5{HT}1{A}
                      {R}ezeptorliganden {WAY} 100635},
      volume       = {3895},
      issn         = {0944-2952},
      school       = {Univ. Köln},
      type         = {Dr. (Univ.)},
      address      = {Jülich},
      publisher    = {Forschungszentrum Jülich GmbH Zenralbibliothek, Verlag},
      reportid     = {PreJuSER-44139, Juel-3895},
      series       = {Berichte des Forschungszentrums Jülich},
      pages        = {VI, 133 p.},
      year         = {2001},
      note         = {Record converted from VDB: 12.11.2012; Köln, Univ., Diss.,
                      2001},
      abstract     = {The serotonergic system with its différent receptor
                      subtypes is one of the most important neuronal transmitter
                      systems in the brain. It is involved in the regulation of
                      various physiological functions and states of mind such as
                      fear, depression and schizophrenia. The radioligand
                      [11C]WAY-100635 (["
                      C]N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-
                      pyridinyl)-cyclohexanecarboxamide) was successfully used in
                      vivo as 5-HTIA antagonist. The aim of the study was to
                      prepare in vivo stable 18F-analogues . New derivatization of
                      WAY 100635 was at first performed by n.c.a. 18F-labelling in
                      4- position of the cyclohexyl group in a one-step reaction.
                      With the diastereomeric model compounds cis/trans
                      ethyl-4-tosylcyclohexanecarboxylate the dependence of
                      various reaction parameters, like temperature, solvent and
                      reaction time, on the radiochemical yield (RCY) was tested.
                      The results were transfered to the WAY derivatives . The
                      best results of n.c.a. 18Ffluorination were obtained at
                      100°C using DMSO as solvent . The radiochemical yield was
                      about $25\%$ for the cis-diastereomer and $5\%$ for the
                      trans-diastereomer of 4-[18F]fluoro-(N-[2-
                      [4-(2-methoxyphenyl)-1-piperazinyl]ethyl)-N-(2-pyridinyl
                      )-cyclohexanecarboxamide. Subsequently, the syntheses of
                      stabilized sulfonamides and sulfinamides as new analogues of
                      the 5-HTIA antagonist WAY 100635 were performed. The
                      derivatives were radiolabelled with [18F]fluoride and [
                      1231]iodide for in vivo applications; namely 4-iodo- and
                      4-fluoro-N-12-[4-
                      (2-methoxyphenyl)-piperazin-1-yl)-ethyll-N-pyridin-2-yl-benzenesulfonamide
                      as well as the corresponding sulfinamide analogues. With the
                      activating sulfonamide substituent différent leaving groups
                      (X = F, Cl, Br, I and N02) were investigated for
                      no-carrier-added aromatic 18F-substitution. Again the effect
                      of various reaction parameters, like temperature, solvent
                      and leaving groups, on the maximum radiochemical yield was
                      tested in model compounds. The results were transfered to
                      the compounds of interest . The 18F-labelled sulfonamides
                      were prepared by nucleophilic aromatic substitution in high
                      RCY of $65\%$ within 15 min using bromine as leaving group
                      at 160°C and DMSO as solvent. The corresponding
                      18F-labelled sulfinamides were not stable under the
                      labelling conditions tested. The formation of
                      [123I]iodo-analogues of sulfonamides was accomplished by
                      Cu(I)-assisted radioiodo-forbromo substitution in acetic
                      acid with over $90\%$ RCY. Finally, the 123I-labelled
                      sulfinamide was prepared via electrophilic destannylation.
                      The RCY of 4-[ 123I]iodo-N-12-[4-(2- methoxyphenyl)
                      -piperazin- 1-yl)-ethyll-N-pyridin-2-yl-benzenesulfinamide
                      was ca. $80\%$ after 2 min in methanol/acetic acid at
                      ambient temperature with chloramine-T as in-situ oxidizing
                      agent. In vitro competition studies with the fluoro- and
                      iodo-sulfonamides and -sulfinamides versus the highly
                      selective 5-HTIA receptor ligand [3H]8-OH-DPAT lead to Ki
                      values of 36 to 112 nM. First biodistribution studies in
                      mice of [18F]fluoro-sulfonamide proved the increased in vivo
                      stability},
      cin          = {INC},
      cid          = {I:(DE-Juel1)VDB53},
      pnm          = {Radiopharmazeutische Chemie},
      pid          = {G:(DE-Juel1)FUEK87},
      typ          = {PUB:(DE-HGF)11 / PUB:(DE-HGF)3},
      url          = {https://juser.fz-juelich.de/record/44139},
}