Novel N-substituted 3α-[bis(4'-fluorophenyl)methoxy]tropane analogues: Selective ligands for the dopamine transporter

Journal of Medicinal Chemistry

Volumn 40, Issue 26, 1997, Pages 4329-4339

  Agoston, Gregory E ^a   Wu, Jae H ^a   Izenwasser, Sari ^a   George, Clifford ^b   Katz, Jonathan ^a   Kline, Richard H ^a   Newman, Amy Hauck ^a  

^a NATIONAL INSTITUTE ON DRUG ABUSE   (United States)

^b NAVAL RESEARCH LABORATORY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

3BETA (4 FLUOROPHENYL) 2BETA TROPANECARBOXYLIC ACID METHYL ESTER; BENZATROPINE MESILATE; CITALOPRAM; COCAINE; DESIPRAMINE; DOPAMINE TRANSPORTER; DOPAMINE UPTAKE INHIBITOR; DRUG VEHICLE; MUSCARINIC M1 RECEPTOR; N (4'' PHENYL N BUTYL) 3ALPHA [BIS(4' FLUOROPHENYL)METHOXY]TROPANE; SEROTONIN TRANSPORTER; SODIUM CHLORIDE; TROPANE DERIVATIVE; UNCLASSIFIED DRUG; VANOXERINE;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; BINDING AFFINITY; CAUDATE NUCLEUS; CONTROLLED STUDY; DOPAMINE UPTAKE; DRUG ABUSE; DRUG DISCRIMINATION; DRUG POTENCY; DRUG SELECTIVITY; DRUG SYNTHESIS; INTRAPERITONEAL DRUG ADMINISTRATION; LIGAND BINDING; LOCOMOTION; MALE; MOUSE; NONHUMAN; PUTAMEN; RAT; RECEPTOR AFFINITY; STRUCTURE ACTIVITY RELATION;

ANIMALS; BINDING, COMPETITIVE; BRAIN; CARRIER PROTEINS; COCAINE; CRYSTALLOGRAPHY, X-RAY; DOPAMINE; DOPAMINE PLASMA MEMBRANE TRANSPORT PROTEINS; DOPAMINE UPTAKE INHIBITORS; LIGANDS; MALE; MEMBRANE GLYCOPROTEINS; MEMBRANE TRANSPORT PROTEINS; MICE; MODELS, MOLECULAR; MOLECULAR STRUCTURE; MOTOR ACTIVITY; NERVE TISSUE PROTEINS; RATS; RECEPTORS, MUSCARINIC; STRUCTURE-ACTIVITY RELATIONSHIP; TROPANES;

EID: 0031434059     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm970525a     Document Type: Article

References (32)

1. Carroll, F. I.; Lewin, A. H.; Kuhar, M. J. Dopamine Transporter Uptake Blockers: Structure-Activity Relationships. Neurotransmitter Transporters: Structure, Function and Regulation; Reith, M. E. A., Eds.; Humana Press Inc.: Totowa, NJ, 1996.
2. (a) Ritz, M. C.; Lamb, R. J.; Goldberg, S. R.; Kuhar, M. J. Cocaine Receptors on Dopamine Transporters are Related to Self-Administration of Cocaine. Science 1987, 237, 1219-1223.
3. (b) Kuhar, M. J.; Ritz, M. C.; Boja, J. W. The Dopamine Hypothesis of the Reinforcing Properties of Cocaine. Trends Neurosci. 1991, 14, 299-301.
4. (a) Newman, A. H.; Allen, A. C.; Izenwasser, S.; Katz, J. L. Novel 3α-(Diphenylmethoxy)tropane Analogs: Potent Dopamine Uptake Inhibitors without Cocaine-like Behavioral Profiles. J. Med. Chem. 1994, 37, 2258-2261.
5. (b) Newman, A. H.; Kline, R. H.; Allen, A. C.; Izenwasser, S.; George, C.; Katz, J. L. Novel 4′Substituted and 4′,4″-Disubstituted 3α-(Diphenylmethoxypropane Analogs as Potent and Selective Dopamine Uptake Inhibitors. J. Med. Chem. 1995, 38, 3933-3940.
6. Holtzman, S. G. Discriminative stimulus effects of drugs: relationship to potential for abuse. In Testing and Evaluation of Drugs of Abuse Modern Methods in Pharmacology; Adler, M. W., Cowan, A., Eds.; Wiley-Liss: New York, 1990; Vol. 6, pp 193-210.
7. Kline, R. H.; Izenwasser, S.; Katz, J. L.; Joseph, D. B.; Bowen, W. D.; Newman, A. H. 3′-Chloro-3α-(Diphenylmethoxy)tropane but not 4′-Chloro-3α-(Diphenylmethoxy)tropane Produces a Cocaine-like Behavioral Profile. J. Med. Chem. 1997, 40, 851-857.
8. Newman, A. H.; Agoston, G. E.; Wu, J. H.; Kline, R. H.; Izenwasser, S.; Katz, J. L. Synthesis, Pharmacology and Molecular Modelling Studies on a Series of N-Substituted 4′,4″-Difluoro-3α-(Diphenylmethoxy)tropane Analogs. In Society for Neuroscience, 26th Annual Meeting, 1996, Vol. 22, Abstract 278-13.
9. (a) Mateka, D.; Rothman, R. B.; Radesca, L.; de Costa, B. R.; Dersch, C. M.; Partilla, J. S.; Pert, A.; Glowa, J. R.; Wojnicki, F. H. E.; Rice, K. C. Development of Novel, Potent and Selective Dopamine Reuptake Inhibitors through Alteration of the Piperazine Ring of 1-[2-(Diphenylmethoxy)ethyl]- and 1-[2-[Bis(4-fluorophenyl)methoxy]etnyl]-4-(3-phenylpropyl)piperazines (GBR 12935 and GBR 12909). J. Med. Chem. 1996, 39, 4704-4716.
10. (b) Matecka, D.; Lewis, D.; Rothman, R. B.; Dersch, C. M.; Wojnicki, F. H. E.; Glowa, J. R.; DeVries, A. C.; Pert, A.; Rice, K. C. Heteroaromatic Analogs of 1-[2-(Diphenylmethoxy)-ethyl] and l-[2-[Bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazines (GBR 12935 and GBR 12909) as High-Affinity Dopamine Reuptake Inhibitors. J. Med. Chem. 1997, 40, 705-716.
11. Dutta, A. K.; Coffey, L. L.; Reith, M. E. A. Highly Selective, Novel Analogs of 4-[2-(Diphenylmethoxy)ethyl]-l-benzylpiperidine for the Dopamine Transporter: Effect of Different Aromatic Substitutions on Their Affinity and Selectivity. J. Med. Chem. 1997, 40, 35-43.
12. Van der Zee, P.; Koger, H. S.; Gootjes, J.; Hespe, W. Aryl 1,4-dialk(en)ylpiperazines as Selective and Very Potent Inhibitors of Dopamine Uptake. Eur. J. Med. Chem.-Chem. Ther. 1980, 15, 363-370.
13. Meltzer, P. C.; Liang, A. Y.; Madras, B. K. 2-Carbomethoxy-3-(diarylmethoxy)-1αH,5αH-tropane Analogs: Synthesis and Inhibition of Binding at the Dopamine Transporter and Comparison with Piperazines of the GBR Series. J. Med. Chem. 1996, 39 371-379.
14. (a) Olofson, R. A.; Martz, J. T.; Senet, J.-P.; Piteau, M.; Malfroot, T. A New Reagent for the Selective, High-Yield N-Dealkylation of Tertiary Amines: Improved Synthesis of Naltrexone and Nalbuhine. J. Org. Chem. 1984, 49, 2081-2082.
15. (b) Olofson, R. A.; Abbott, D. E. Tests of a Piperidino Mask for the Protection of Functionalized Carbon Sites in Multistep Synthesis. J. Org. Chem. 1984, 49, 2795-2799.
16. (c) Peet, N. N-Demethylation of Dextromethorphan. J. Pharm. Sci. 1980, 69, 1447-1448.
17. The alkylbromide precursors for 8g,h were prepared using van der Zee's protocol. See ref 9.
18. Kozikowski A. P.; Saiah, M. K. E.; Bergmann, J. S.; Johnson, K. M. Structure-Activity Relationship Studies of N-Sulfonyl Analogs of Cocaine: Role of Ionic Interaction of Cocaine Binding, J. Med. Chem. 1994, 37, 3440-3442.
19. Madras, B. K.; Pristupa, Z. B.; Nizik, H. B.; Liang, A. Y.; Blundell, P.; Gonzalez, M. D.; Meltzer, P. C. Nitrogen-Based Drugs are not Essential for Blockade of Monoamine Transporters. Synapse 1996, 24, 340-348.
20. Abraham, P.; Pitner, J. B.; Lewin, A. H.; Boja, J. W.; Kuhar, M. J.; Carroll, F. I. N-Modified Analogs of Cocaine: Synthesis and Inhibition of Binding to the Cocaine Receptor. J. Med. Chem. 1992, 35, 141-144.
21. Meltzer, P. C.; Liang, A. Y.; Blundell, P.; Gonzalez, M. D.; Chen, Z.; George, C.; Madras, B. K. 2-Carbomethoxy-3-aryl-8-oxabicyclo[3.2.1]octanes: Potent Non-Nitrogen Inhibitors of Monoamine Transporters. J. Med. Chem. 1997, 40, 2661-2673.
22. SYBYL version 6.3 available from Tripos, 1699 S Hanley Rd, Suite 303, St. Louis, MO 63144.
23. Dewar, M. J. S.; Zoebisch, E. G.; Healy, E. F.; Stewart, J. J. P. AMI: A New General Purpose Quantum Mechanical Molecular Model. J. Am. Chem. Soc. 1985, 107, 3902-3909.
24. MOPAC 6.0 available from Quantum Chemistry Program Exchange no. 455.
25. Sheldrick, G. M. (1995). SHELXTL PC Release 5.0 for Siemens P4 Crystal Research System. Siemens Analytical X-ray Instruments, Madison, WI.
26. 2.
27. Snedecor, G. W.; Cochran, W. G. Statistical Methods, 6th ed.; Iowa State University Press: Ames, IA, 1967; pp 135-171.
28. Izenwasser, S.; Werling, L. L.; Cox, B. M. Comparison of the Effects of Cocaine and Other Inhibitors of Dopamine Uptake in Rat Striatum, Nucleus Accumbens, Olefactory Tubercle, and Medial Prefontal Cortex. Brain Res. 1990, 520, 220-239.
29. 3H]Imipramine. J. Pharmacol. Exp. Ther. 1987, 242, 364-371 with modifications,
30. (b) Brown, N. L.; Sirgue, O.; Worcel, M. The Effects of Some Slow Channel Blocking Drugs on High Affinity Serotonin Uptake by Rat Brain Synaptosomes. Eur. J. Pharmacol 1986, 123, 161-165.
31. 3H]Despramine Binding in the Peripheral and Central Nervous System: A Specific Site Associated with the Neuronal Uptake of Noradrenaline. Eur. J. Pharmacol. 1982, 78, 345-351 with modifications,
32. 3H]-DMI Binding is Associated with Neuronal Noradrenaline Uptake in the Periphery and the Central Nervous System. Eur. J. Pharmacol. 1981, 72, 423.