Nuclear Medicine and Biology
Volume 34, Issue 5 , Pages 531-539 , July 2007

New 2α-tropane amides as potential PET ligands for the dopamine transporter

  • Birte Drewes

      Affiliations

    • Institut für Nuklearchemie, Forschungszentrum Jülich GmbH, 52425 Jülich, Germany
    • Corresponding Author InformationCorresponding author. Tel.: +49 2461 61 6907; fax: +49 2461 61 2535.
    • ,
  • Wiebke Sihver

      Affiliations

    • Institut für Nuklearchemie, Forschungszentrum Jülich GmbH, 52425 Jülich, Germany
    • ,
  • Sabine Willbold

      Affiliations

    • Zentralabteilung für chemische Analysen, Forschungszentrum Jülich GmbH, 52425 Jülich, Germany
    • ,
  • Ray A. Olsson

      Affiliations

    • Institut für Nuklearchemie, Forschungszentrum Jülich GmbH, 52425 Jülich, Germany
    • ,
  • Heinz H. Coenen

      Affiliations

    • Institut für Nuklearchemie, Forschungszentrum Jülich GmbH, 52425 Jülich, Germany

Received 7 February 2007 ,Revised 12 March 2007 ,Accepted 14 April 2007.

References 

  1. Schenk JO. The functioning neuronal transporter for dopamine: kinetic mechanisms and effects of amphetamines, cocaine and methylphenidate. Prog Drug Res. 2002;59:113–131
  2. Torres GE, Carneiro A, Seamans K, Fiorentini C, Sweeney A, Yao WD, et al. Oligomerization and trafficking of the human dopamine transporter. J Biol Chem. 2003;278:2731–2739
  3. Giros B, Jaber M, Jones SR, Wightman RM, Caron MG. Hyperlocomotion and indifference to cocaine and amphetamine in mice lacking the dopamine transporter. Nature. 1996;379:606–612
  4. Horn A. Characteristics of transport in dopaminergic neurons. In:  Paton DM editors. The mechanism of neuronal and extraneuronal transport of catecholamines. New York: Raven Press; 1976;p. 195–214
  5. Clarke RL, Daum SJ, Gambino AJ, Aceto MD, Pearl J, Levitt M, et al. Compounds affecting the central nervous system. 4.3β-Phenyltropane-2-carboxylic esters and analogs. J Med Chem. 1973;16:1260–1267
  6. Pimoule C, Schoemaker H, Javoy-Agid F, Scatton B, Agid Y, Langer SZ. Decrease in [3H]cocaine binding to the dopamine transporter in Parkinson's disease. Eur J Pharmacol. 1983;95:145–146
  7. Kuhar MJ, Ritz MC, Boja JW. The dopamine hypothesis of the reinforcing properties of cocaine. Trends Neurosci. 1991;14:299–302
  8. Innis RB, Seibyl P, Scanley BE, Laruell M, Abi-Dargham A, Wallace E. Single photon emission computed tomographic imaging demonstrates loss of striatal dopamine transporters on parkinson disease. Proc Natl Acad Sci U S A. 1993;90:11965–11969
  9. Seibyl JP, Marek KL, Quinlan D, Sheff K, Zoghbi S, Zea-Ponce Y, et al. Decreased single-photon emission computed tomographic [123I]β-CIT striatal uptake correlates with symptom severity in Parkinson's disease. Ann Neurol. 1995;8:589–598
  10. Singh S. Chemistry, design, and structure–activity relationship of cocaine antagonists. Chem Rev. 2000;100:925–1024
  11. Carroll FI, Gao Y, Rahman MA, Abraham P, Parham K, Lewin AH, et al. Synthesis, ligand binding, QSAR, and CoMFA study of 3β-(p-substituted phenyl)tropane-2β-carboxylic acid methyl esters. J Med Chem. 1991;34:2719–2725
  12. Chaly T, Dhawan V, Kazumata K, Antonini A, Margouleff C, Dahl JR, et al. Radiosynthesis of [18F]-N-3-fluorpropyl-2β-carbomethoxy-3-β-(4-iodophenyl) nortropane and the first human study with positron emission tomography. Nucl Med Biol. 1996;23:999–1004
  13. Emond P, Garreau L, Chalon S, Boazi M, Caillet M, Bricard J, et al. Synthesis and ligand binding of nortropane derivatives: N-substituted 2β-carbomethoxy-3β-(4′-iodophenyl)nortropane and N-(3-Iodoprop-(2E)-enyl)-2β-carbomethoxy-3β-(3′, 4′-disubstituted phenyl)nortropane. New high-affinity and selective compounds for the dopamine transporter. J Med Chem. 1997;40:1366–1372
  14. Wilson AA, DaSilva JN, Houle S. Synthesis of two radiofluorinated cocaine analogues using distilled 2-[18F]Fluoroethylbromid. Appl Radiat Isot. 1995;46:765–770
  15. Goodmann MM, Kilts CD, Keil R, Shi B, Martarello L, Xing D, et al. 18F-Labeled FECNT: a selective radioligand for PET imaging of brain dopamine transporters. Nucl Med Biol. 2000;27:1–12
  16. Dolle F, Emond P, Mavel S, Demphel S, Hinnen F, Mincheva Z, et al. Synthesis, radiosynthesis and in vivo preliminary evaluation of [C-11]LBT-999, a selective radioligand for the visualisation of the dopamine transporter with PET. Bioorg Med Chem. 2006;14:1115–1125
  17. Chen P, Kilts CD, Camp VM, Ely TD, Keil R, Malveaux E, et al. Synthesis, characterization and in vivo evaluation of (N-((E)-4 [18F]fluorobut-2-en-1-yl)-2β-carbomethoxy-3β-((4-substituted-phenyl)nortropanes for imaging DAT by PET. J Labelled Cmpd Radiopharm. 1999;42:S400–S402
  18. Goodman MM, Chen P. Fluoroalkenyl nortropanes. WO 00064490 A1: U.S. Patent 2000;37.
  19. Kotian P, Mascarella WS, Abraham P, Lewin AH, Boja JW, Kuhar MJ, et al. Synthesis, ligand binding, and quantitative structure–activity relationship study of 3β-(4′-substituted phenyl)-2β-heterocyclic tropanes: evidence for an electrostatic interaction at the 2β-position. J Med Chem. 1996;39:2753–2763
  20. Roland D, Schönbächler PM, Kneifel S, Vollenweider FX, Buck A, Burger C, et al. PET imaging of dopamine transporters in the human brain using [11C]-β-CPPIT, a cocaine derivative lacking the 2β-ester function. Nucl Med Biol. 2002;29:19–27
  21. Thiruvazhi M, Abraham P, Kuhar MJ, Carroll FI. Synthesis of the isomers of (1R)-3-(phenylthio)tropane-2-carboxylic acid methyl ester. A new class of ligands for the dopamine transporter. Chem Commun. 1997;21:555–556
  22. Zhao LY, Kozikowski AP. Synthesis of the 2 beta,3 beta-, 2 alpha,3 beta-, 2 beta,3 alpha- and 2 alpha,3 alpha- isomers of 6 beta-hydroxy-3-(p-tolyl)tropane-2-carboxylic acid methyl ester. Tetrahedron Lett. 1999;40:4961–4964
  23. Carroll FI, Runyon SP, Abraham P, Navarro H, Kuhar MJ, Pollard GT, et al. Monoamine transporter binding, locomotor activity, and drug discrimination properties of 3-(4-substituted-phenyl)tropane-2-carboxylic acid methyl ester isomers. J Med Chem. 2004;47:6401–6409
  24. Lomenzo SA, Izenwasser S, Katz JL, Terry PD, Zhu N, Klein CL, et al. Synthesis, structure, dopamine transporter affinity, and dopamine uptake inhibition of 6-alkyl-3-benzyl-2-[(methoxycarbonyl)methyl]tropane derivatives. J Med Chem. 1997;40:4406–4414
  25. Carroll FI, Abraham P, Kuzemko MA, Gray JL, Lewin AH. Synthesis and cocaine receptor affinities of 3-phenyl-2-(3′-methyl-1,2,4-oxadiazole-5′-yl)tropane isomers. J Chem Soc Chem Commun. 1993;1:44–46
  26. Carroll FI, Gray LJ, Abraham P, Kuzemko MA, Lewin AH, Boja JW, et al. 3-Aryl-2-(3′-substituted-1′,2′,4′-oxadiazol-5′-yl)tropane analogs of cocaine: affinities at the cocaine binding site at the dopamine, serotonin, and norepinephrine transporters. J Med Chem. 1993;36:2886–2890
  27. Carroll FI, Lewin AH, Abraham P, Parham K, Boja JW, Kuhar MJ. Synthesis and ligand binding of cocaine isomers at the cocaine receptor. J Med Chem. 1991;34:883–886
  28. Sihver W, Drewes B, Schulze A, Olsson RA, Coenen HH. Evaluation of novel tropane analogues in comparison with binding characteristics of [18F]FP-CIT and [131I]β-CIT. Nucl Med Biol. 2007;34:211–219
  29. Neumeyer JL, Wang S, Yigong G, Milius RA, Kula NS, Campbell A, et al. N-ω-Fuoroalkyl analogs of (1R)-2β-carbomethoxy-3β-(4-iodophenyl)-tropane (β-CIT): radiotracers for positron emission tomography and single photon emission computed tomography imaging of dopamine transporters. J Med Chem. 1994;37:1558–1561
  30. Meltzer PC, Liang AL, Brownell AÖ, Elmaleh DR, Madras BK. Substituted 3-phenyltropane analogs of cocaine: synthesis, inhibition of binding at cocaine recognition sites, and positron emission tomography imaging. J Med Chem. 1993;36:855–862
  31. Xu L, Trudell ML. Stereoselective synthesis of 2β-carbomethoxy-3β-phenyltropane derivates. Enhanced stereoselectivity observed for the conjugate addition reaction of phenylmagnesiumbromid derivatives with anhydro dichloromethane. J Heterocycl Chem. 1996;33:2037–2039
  32. Milius RA, Saha JK, Madras BK, Neumeyer JL. Synthesis and receptor binding of N-substituted tropane derivatives. High-affinity ligands for the cocaine receptor. J Med Chem. 1991;34:1728–1731
  33. Swahn CG, Halldin C, Gunther I, Günther I, Patt J, Ametamey S. Synthesis of unlabelled, H-3- and I-125-labelled beta-CIT and its omega-fluoroalkyl analogues beta-CIT-FE and beta-CIT-FP, including synthesis of precursors. J Labelled Compd Radiopharn. 1996;38:675–685
  34. Carroll FI, Gao YG, Abraham P, Lewin AH, Lew R, Patel A, et al. Probes for the cocaine receptor. Potentially irreversible ligands for the dopamine transporter. J Med Chem. 1992;35:1813–1817
  35. Shioiri T, Yokoyama Y, Kasai Y, Yamada S. Phosphorous in organic synthesis. Tetrahedron. 1976;32:2211–2217
  36. Edgell WF, Parts L. Synthesis of alkyl and substituted alkyl fluorides from p-toluenesulfonic acid esters. The preparation of p-toluenesulfonic acid esters of lower alcohols. J Am Chem Soc. 1955;77:4899–4902
  37. Wilson AA, DaSilva JN, Houle S. Synthesis of two radiofluorinated cocaine analogues using distilled 2-[18F]fluoroethylbromid. Appl Radiat Isot. 1995;46:765–770
  38. Carroll FI, Kotian P, Dehghani A, Gray JL, Kuzemko MA, Parham KA, et al. Cocaine and 3β-(4′-substituted phenyl)tropane-2β-carbocylic acid ester and amide analogues. New high-affinity and selective compounds for the dopamine transporter. J Med Chem. 1995;38:379–388
  39. Krebs B, Flörke U. N-(2-Fluoroethyl)-3 beta-(4-iodophenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2 alpha-carboxamide: a new cocaine derivative with equatorially attached ligands. Acta Cryst. 2004;C60:o118–o119
  40. Xu L, Trudell ML. Stereoselective synthesis of 2β-carbomethoxy-3β-phenyltropane derivates. Enhanced stereoselectivity observed for the conjugate addition reaction of phenylmagnesiumbromid derivatives with anhydro dichloromethane. J Heterocycl Chem. 1996;33:2037–2039
  41. Gee AD, Moldt P, Gjedde A. The labelling of a novel tropane derivative [C-11]NS 2214 (BMS-204756) — an inhibitor of the dopamine transporter. J Labelled Compd Radiopharm. 1997;39:959–972
  42. Lidov HG, Grzanna R, Molliver ME. Serotonin innervation of the cerebral-cortex in the rat — immunohistochemical analysis. Neuroscience. 1980;5:207–227
  43. Boja JW, Cline EJ, Carroll FI, Lewin AH, Philip A, Dannals R, et al. High potency cocaine analogs — neurochemical, imaging and behavioural-studies. Ann N Y Acad Sci. 1992;654:282–291
  44. Monteiro-Riviere NA, Tumbleson ME. In:  Tumbleson ME editors. Swine in biomedical research. vol 1:New York: Plenum; 1986;p. 437–440
  45. Dickerson JWT. Dobbing. Effect of undernutrition on postnatal development of brain and cord in pigs. J Proc R Soc Lond Ser B Biol Sci. 1967;166:384
  46. Munkeby BH, Lyng K, Froen JF, Winther-Larssen EH, Rosland JH, Smith HJ, et al. Morphological and hemodynamic magnetic resonance assessment of early neonatal brain injury in a piglet model. J Magn Reson Imaging. 2004;20:8–15
  47. Miller GM, Yatin SM, De La Garza R, Goulet M, Madras BK. Cloning of dopamine, norepinephrine and serotonin transporters from monkey brain: relevance to cocaine sensitivity. Brain Res Mol Brain Res. 2001;87:124–143
  48. Peng X, Zhang A, Kula NS, Baldessarini RJ, Neumeyer JL. Synthesis and transporter affinities of novel phenyltropane derivatives as potential positron emission tomography (PET) imaging agents. Bioorg Med Chem. 2004;14:5635–5639
  49. Krebs B, Bier D, Sihver W, Holschbach M, Coenen HH. New promising radiofluorinated dopamine transporter ligands: synthesis, n.c.a radiofluorination and preliminary evaluation. J Labelled Compd Radiopharm. 2003;46:S53
  50. Chalon S, Garreau L, Emond P, Zimmer L, Vilar MP, Besnard JC, et al. Pharmacological characterisation of (E)-N-(3-iodoprop-2-enyl)-2β-carbomethoxy-3β-(4′-methylphenyl)nortropane as a selective and potent inhibitor of the neuronal dopamine transporter. Pharmacol Exp Ther. 1999;291:648–654
  51. Halldin C, Erixon-Lindroth N, Pauli S, Chou YH, Okubo Y, Karlsson P, et al. [C-11]PE2I: a highly selective radioligand for PET examination of the dopamine transporter in monkey and human brain. Eur J Nucl Med Mol Imaging. 2003;30:1220–1230
  52. Guilloteau D, Emond P, Baulieu JL, Garreau L, Frangin Y, Pourcelot L, et al. Exploration of the dopamine transporter: in vitro and in vivo characterization of a high-affinity and high-specificity iodinated tropane derivative (E)-N-(3-iodoprop-2-enyl)-2β-carbomethoxy-3β-(4′-methylphenyl)nortropane (PE2I). Nucl Med Biol. 1998;25:331–337
  53. Dall AM, Danielsen EH, Sorensen JC, Andersen F, Moller A, Zimmer J, et al. Quantitative [F-18]fluorodopa/PET and histology of fetal mesencephalic dopaminergic grafts to the striatum of MPTP-poisoned minipigs. Cell Transplant. 2002;11:733–746
  54. Minuzzi L, Olsen AK, Bender D, Arnfred S, Grant R, Danielsen EH, et al. Quantitative autoradiography of ligands for dopamine receptors and transporters in brain of Gottingen minipig: comparison with results in vivo. Synapse. 2006;59:211–219
  55. Lehtinen S. Neurotoxicity in children after treatment for acute lymphoblastic leukaemia and methotrexate neurotoxicity in a controlled animal model. Acta Univ Ouluensis, D Med. 2003;728:ISBN: 951-42-7032-0; ISSN: 0355-3221
  56. Lewin AH, Gao YG, Abraham P, Boja JW, Kuhar MJ, Carroll FI. 2.beta.-Substituted analogs of cocaine. Synthesis and inhibition of binding to the cocaine receptor. J Med Chem. 1992;35:135–140

PII: S0969-8051(07)00120-5

doi: 10.1016/j.nucmedbio.2007.04.007

Nuclear Medicine and Biology
Volume 34, Issue 5 , Pages 531-539 , July 2007

Article Tools

* Image Usage & Resolution