Synthesis, in vitro characterization, and radiolabeling of N,N-dimethyl-2-(2′-amino-4′-substituted-phenylthio)benzylamines: Potential candidates as selective serotonin transporter radioligands

Journal of Medicinal Chemistry

Volumn 48, Issue 13, 2005, Pages 4254-4265

  Jarkas, Nachwa ^a   McConathy, Jonathan ^a   Voll, Ronald J ^a   Goodman, Mark M ^a,b  

^a EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b EMORY UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

3BETA (4 FLUOROPHENYL) 2BETA TROPANECARBOXYLIC ACID METHYL ESTER; 3BETA (4 IODOPHENYL) 2BETA TROPANECARBOXYLIC ACID METHYL ESTER; BENZYLAMINE DERIVATIVE; CITALOPRAM; DOPAMINE TRANSPORTER; N,N DIMETHYL 2 (2' AMINO 4' ETHENYLPHENYLTHIO) BENZYLAMINE; N,N DIMETHYL 2 (2' AMINO 4' ETHYLPHENYLTHIO) BENZYLAMINE; N,N DIMETHYL 2 (2' AMINO 4' FLUOROETHYLPHENYLTHIO) BENZYLAMINE; N,N DIMETHYL 2 (2' AMINO 4' FLUOROPROPYLPHENYLTHIO) BENZYLAMINE; N,N DIMETHYL 2 (2' AMINO 4' HYDROXYETHYLPHENYLTHIO) BENZYLAMINE; N,N DIMETHYL 2 (2' AMINO 4' HYDROXYMETHYLPHENYLTHIO) BENZYLAMINE; N,N DIMETHYL 2 (2' AMINO 4' HYDROXYPROPYLPHENYLTHIO) BENZYLAMINE; N,N DIMETHYL 2 (2' AMINO 4' METHYLPHENYLTHIO) BENZYLAMINE; N,N DIMETHYL 2 (2' AMINO 4' PHENYLTHIO) BENZYLAMINE; N,N DIMETHYL 2 (2' AMINOPHENYLTHIO) BENZYLAMINE; NISOXETINE; NORADRENALIN TRANSPORTER; RADIOLIGAND; SEROTONIN TRANSPORTER; TRACER; UNCLASSIFIED DRUG;

ARTICLE; ASSAY; BINDING AFFINITY; HUMAN; HUMAN CELL; IN VITRO STUDY; ISOTOPE LABELING; METHYLATION; POSITRON EMISSION TOMOGRAPHY; PROTEIN FUNCTION; RADIOCHEMISTRY; SUBSTITUTION REACTION; SYNTHESIS;

BENZYLAMINES; BINDING, COMPETITIVE; CITALOPRAM; COCAINE; DOPAMINE PLASMA MEMBRANE TRANSPORT PROTEINS; HUMANS; IODINE RADIOISOTOPES; ISOTOPE LABELING; LIGANDS; MEMBRANE GLYCOPROTEINS; MEMBRANE TRANSPORT PROTEINS; NERVE TISSUE PROTEINS; NOREPINEPHRINE PLASMA MEMBRANE TRANSPORT PROTEINS; RADIOLIGAND ASSAY; RADIOPHARMACEUTICALS; RECOMBINANT PROTEINS; SEROTONIN PLASMA MEMBRANE TRANSPORT PROTEINS; SULFIDES; SYMPORTERS; TRITIUM;

EID: 21244456121     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm050079o     Document Type: Article

References (50)

1. Sur, C.; Betz, H.; Schloss, P. Immunocytochemical detection of the serotonin transporter in rat brain. Neuroscience 1996, 73, 217-231.
2. Tao-Cheng, J. H.; Zhou, F. C. Differential polarization of serotonin transporters in axons versus soma-dendrites: an immunogold electron microscopy study. Neuroscience 1999, 94, 821-830.
3. 3H]5-hydroxytryptamine. Neuroscience 1981, 6, 115-138.
4. Steinbusch, H. W. M. Distribution of serotonin-immunoreactivity in the central nervous system of the rat-cell bodies and terminals. Neuroscience 1981, 6, 557-618.
5. Laasko, A.; Hietala, J. PET studies of brain monoamine transporters. Curr. Pharm. Des. 2000, 6, 1611-1623.
6. 11C]-sertraline. Int. J. Radiat. Appl. Instrum., Part A 1989, 40, 147-151.
7. Owens, M. J.; Nemeroff, C. B. The serotonin transporter and depression. Depression Anxiety 1998, 8, 5-6.
8. Owens, M. J.; Nemeroff, C. B. Role of serotonin in the pathophysiology of depression: focus on the serotonin transporter. Clin. Chem. 1994, 40, 288-295.
9. Lucki, I. The spectrum of behaviors influenced by serotonin. Biol. Psychiatry 1998, 44, 151-162.
10. 3H]-Imipramine Binding Sites in Control and Parkinsonian Brain. Eur. J. Pharmacol. 1985, 117, 71-80.
11. 3H]Citalopram. Neuroscience 1993, 54, 691-699.
12. Sorgi, K. L.; Maryanoff, C. A.; McComsey, D. F.; Graden, D. W.; Maryanoff, B. E. Asymmetric induction in an enammonium-iminium rearrangement. Mechanistic insight via NMR, deuterium labeling, and reaction rate studies. Application to the stereoselective synthesis of pyrroloisoquinoline antidepressants. J. Am. Chem. Soc. 1990, 112, 3567-3583.
13. Jagust, W. J.; Eberling, J. L.; Biegon, A.; Taylor, S. E.; Van-Brocklin, H. F.; Jordan, S.; Hanrahan, S. M.; Roberts, J. A.; Brennan, K. M.; Mathis, C. A. Iodine-123-5-iodo-6-nitroquipazine: SPECT radiotracer to image the serotonin transporter. J. Nucl. Med. 1996, 37, 1207-1214.
14. Helfenbein, J.; Sandell, J.; Halldin, C.; Chalon, S.; Emond, P.; Okubo, Y.; Chou, Y.-H.; Frangin, Y.; Douziech, L.; Gareau, L.; Swahn C-G.; Besnard, J.-C.; Farde, L.; Guilloteau, D. PET examination of three potent cocaine derivatives as specific radioligands for the serotonin transporter. Nucl. Med. Biol. 1999, 26, 491-499.
15. 11C](+)McN5652. Synapse 1995, 20, 37-43.
16. 11C]AFM. J. Cereb. Blood Flow. Metab. 2002, 22, 1377-1398.
17. Blough, B. E.; Abraham, P.; Mills, A. C.; Lewin, A. H.; Boja, J. W.; Scheffel, U.; Kuhar, M. J.; Carroll F. I. 3β-(4-ethyl-3-iodophenyl) nortropane-2-beta-carboxylic acid methyl ester as a high-affinity selective ligand for the serotonin transporter. J. Med. Chem. 1997, 40, 3861-3864.
18. Goodman, M. M.; Chen, P.; Kilts, C. D.; Ely, T. D.; Camp, V. M.; Malveaux, E. J.; Votaw, J.; Davis, M.; Owens, M. Fluorine-18 labeled 2β-carbomethoxy-3β-(4′-(2-fluoroisopropenyl)phenyl)-nortropane (FIPPNT) synthesis, characterization and tissue distribution of a potential radioligand for mapping serotonin transporter sites by PET. Book Abstr. Int. Chem. Congr. Pac. Basin Soc. 2000, 1, 104.
19. Goodman, M. M.; Chen, P.; Kilts, C. D.; Ely, T.; Davis, M. and Votaw, J. Fluorine-18 Serotonin Transporter Ligands. In Synthesis and Applications of Isotopically Labelled Compounds; Pleiss, U., Voges, R., Eds.; Wiley: New York, 2001; pp 362-366.
20. Goodman, M. M.; Chen, P.; Plisson, C.; Martarello, L.; Galt, J.; Votaw, J. R.; Kilts, C. D.; Malveaux, G.; Camp, V. M.; Shi, B.; Ely, T. D.; Howell, L.; McConathy, J.; Nemeroff, C. B. Synthesis and characterization of iodine-123 labeled 2β-carbomethoxy-3β-(4′-((Z-2-iodoethenyl)phenyl) nortropane. A ligand for in vivo imaging of serotonin transporters by single-photon-emission-tomography. J. Med. Chem. 2003, 46, 925-935.
21. Plisson, C.; McConathy, J.; Martarello, L.; Malveaux, E. J.; Camp, V. M.; Williams, L.; Votaw J. R.; Goodman, M. M. Synthesis, Radiosynthesis, and Biological Evaluation of Carbon-11 and Iodine-123 Labeled 2β-Carbomethoxy- 3β-[4′-((Z)-2-halo-ethenyl)phenyl]tropanes: Candidate Radioligands for in Vivo Imaging of the Serotonin Transporter. J. Med. Chem. 2004, 47, 1122-1135.
22. 123I]IDAM, 5-iodo-2-((2-((dimethylamino)methyl)phenyl) thio) benzyl alcohol. J. Med. Chem. 1999, 42, 333-335.
23. 123I]IDAM as a novel single-photon emission tomography tracer for serotonin transporters. Eur. J. Nucl. Med. 1999, 26, 844-853.
24. 123I]IDAM. Eur. J. Nucl. Med. 1999, 26, 854-861.
25. 125I]ADAM to serotonin transporters in rat brain. Synapse 2000, 38, 403-412.
26. Oya, S.; Choi, S.-R.; Hou, C.; Mu, M.; Kung, M.-P.; Acton, P. D.; Siciliano, M.; Kung, H. F. 2-((2-((dimethylamino)methyl)phenyl)-thio)-5- iodophenylamine (ADAM): an improved serotonin transporter ligand. Nucl. Med. Biol. 2000, 27, 249-254.
27. 123I]IDAM and SPECT. J. Nucl. Med. 2001, 42, 1556-1562.
28. 123I-ADAM: a serotonin transporter imaging agent. J. Nucl. Med. 2004, 45, 834-841.
29. 11C]ADAM: a potential radioligand for the serotonin transporter exploration by PET. J. Labelled Compd. Radiopharm. 2001, 44, 113-120.
30. 11C]-DASB. Eur. J. Nucl. Med. 2000, 27, 1719-1722.
31. Emond, P.; Vercouillie, J.; Innis, R.; Chalon, S.; Mavel, S.; Frangin, Y.; Halldin, C.; Besnard, J.-C.; Guilloteau, D. Substituted diphenyl sulfides as selective serotonin transporter ligands: synthesis and in vivo evaluation. J. Med. Chem. 2002, 45, 1253-1258.
32. Tarkiainen, J.; Vercouillie, J.; Emond, P.; Sandell, J.; Hiltunen, J.; Frangin, Y.; Guilloteau, D.; Halldin, C. Carbon-11 labeling of MADAM in two different positions: a highly selective PET radioligand for the serotonin transporter. J. Labelled Compd. Radiopharm. 2001, 44, 1013-1023.
33. Jarkas, N.; McConathy, J.; Ely, T.; Kilts, C. D.; Votaw, J. R.; Goodman, M. M. Synthesis and radiolabeling of new derivatives of ADAM, potential candidates as SERT imaging agents for PET. J. Labelled Compd. Radiopharm. 2001, 44, S204-S206.
34. Huang, Y.; Bae, S.-A.; Zhu, Z.; Guo, N.; Hwang, D.-R.; Laruelle, M. Fluorinated analogues of ADAM as new PET radioligands for the serotonin transporter: synthesis and pharmacological evaluation. J. Labelled Compd. Radiopharm. 2001, 44 (supp. 1), S18-S20.
35. 11C]DAPA). Nucl. Med. Biol. 2002, 29, 741-751.
36. 11C-EADAM: an attractive PET radioligand for serotonin transporters (SERT). J. Nucl. Med. 2002, 43,164P.
37. 11C]-HOMADAM: a new diarylsulfide SERT PET imaging agent. J. Nucl. Med. 2003, 44, 148P.
38. 11C]AFE is a selective serotonin transporter ligand with fast brain uptake kinetics. Nucl. Med. Biol. 2004, 31, 983-994.
39. The thiobenzamide 9a was obtained from thiosalicylic acid following the procedure described in ref 22.
40. Ethyl thiosalicylate 9b was prepared by refluxing thiosalicylic acid in absolute ethanol with concentrated sulfuric acid for 6 days.
41. Jarkas, N.; McConathy, J.; Votaw, J. R.; Voll, R. J.; Malveaux, E. J.; Camp, V. M.; Williams, L.; Goodman, R. R.; Kilts, C. D.; Goodman, M. M. Synthesis and characterization of EADAM: a selective radioligand for mapping the brain serotonin transporters by positron emission tomography. Nucl. Med. Biol. 2005, 32, 75-86.
42. Kalinin, A. V.; Bower, J. F.; Riebel, P.; Snieckus, V. The direct orthometalation-Ullmann connection. A new Cu(I)-catalysed variant for the synthesis of substituted diaryl ethers. J. Org. Chem. 1999, 64, 2986-2987.
43. Jung, M. E.; Dansereau, M. K. Benzo[H]-1, 6-naphthyridine synthesis via intramolecular Diels-Alder reactions of aryl oxazoles: synthetic approach to 2-bromoleptoclinidinone. Heterocycles 1994, 39, 767-778.
44. Middleton, W. J. New fluorinating reagents. Dialkylaminosulfur fluorides. J. Org. Chem. 1975, 40, 574-578.
45. Pandey, G.; Bagul, T. D.; Sahoo, A. K. [3+2] Cycloaddition of nonstabilized azomethine ylides. 7. Stereoselective synthesis of epibatidine and analogues. J. Org. Chem. 1998, 63, 760-768.
46. Lemaire, C.; Plenevaux, A.; Aerts, J.; Del Fiore, G.; Brihaye, C.; Le Bars, D.; Comar, D.; Luxen, A. Solid phase extraction - an alternative to the use of rotaty evaporators for solvent removal in the rapid formulation of PET radio pharmaceuticals. J. Labelled Compd. Radiopharm. 1999, 42, 63-75.
47. 11C-Labeled 2-(Phenylthio)araalkylamines. J. Med. Chem. 2000, 43, 3103-3110.
48. 3]-carbomethoxy-3β- aryltropanes: radiotracers for the dopamine transporter. J. Labelled Compd. Radiopharm. 1994, 34, 759.
49. Wilson, A. A.; Houle, S. Radiosynthesis of carbon-11 labelled N-methyl-2-(arylthio)benzylamines: potential radiotracers for the serotonin reuptake receptor. J. Labelled Compd. Radiopharm. 1999, 42, 1277-1288.
50. Owens, M. J.; Morgan, W. N.; Plott, S. J.; Nemeroff, C. B. Neurotransmitter receptor and transporter binding profile of antidepressant and their metabolites. J. Pharmacol. Exp. Ther. 1997, 283, 1305-1322.