Development of 3-phenyltropane analogues with high affinity for the dopamine and serotonin transporters and low affinity for the norepinephrine transporter

Journal of Medicinal Chemistry

Volumn 51, Issue 24, 2008, Pages 8048-8056

  Jin, Chunyang ^a   Navarro, Hernán A ^a   Carroll, F Ivy ^a  

^a RTI INTERNATIONAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

3BETA (3 BROMO 4 METHOXYPHENYL)TROPANE 2BETA CARBOXYLIC ACID METHYL ESTER; 3BETA (3 FLUORO 4 METHOXYPHENYL)TROPANE 2BETA CARBOXYLIC ACID METHYL ESTER; 3BETA (3 IODO 4 METHOXYPHENYL)TROPANE 2BETA CARBOXYLIC ACID METHYL ESTER; 3BETA (3,5 DIBROMO 4 METHOXYPHENYL)TROPANE 2BETA CARBOXYLIC ACID METHYL ESTER; 3BETA (3,5 DIIODO 4 METHOXYPHENYL)TROPANE 2BETA CARBOXYLIC ACID METHYL ESTER; 3BETA (4 ETHOXYPHENYL)TROPANE 2BETA CARBOXYLIC ACID METHYL ESTER; 3BETA (4 METHOXYPHENYL) 2BETA [3 (4' METHYLPHENYL)ISOXAZOL 5 YL]TROPANE; 3BETA (4 METHOXYPHENYL)TROPANE 2BETA CARBOXYLIC ACID 2 (3 IODO 4 AMINOPHENYL)ETHYL ESTER; 3BETA (4 METHOXYPHENYL)TROPANE 2BETA CARBOXYLIC ACID 2 (3,5 DIBROMO 4 AMINOPHENYL)ETHYL ESTER; 3BETA (4 METHOXYPHENYL)TROPANE 2BETA CARBOXYLIC ACID 2 (3,5 DIIODO 4 AMINOPHENYL)ETHYL ESTER; 3BETA (4 METHOXYPHENYL)TROPANE 2BETA CARBOXYLIC ACID 2 (4 ACETYLAMINOPHENYL)ETHYL ESTER; 3BETA (4 METHOXYPHENYL)TROPANE 2BETA CARBOXYLIC ACID 2 (4 AMINOPHENYL)ETHYL ESTER; 3BETA (4 METHOXYPHENYL)TROPANE 2BETA CARBOXYLIC ACID 2 (4 NITROPHENYL)ETHYL ESTER; 3BETA (4 METHOXYPHENYL)TROPANE 2BETA CARBOXYLIC ACID CYCLOBUTYL ESTER; 3BETA (4 METHOXYPHENYL)TROPANE 2BETA CARBOXYLIC ACID CYCLOPROPYL ESTER; 3BETA (4 METHOXYPHENYL)TROPANE 2BETA CARBOXYLIC ACID ISOPROPYL ESTER; 3BETA (4 METHOXYPHENYL)TROPANE 2BETA CARBOXYLIC ACID METHYL ESTER; 3BETA (4 METHOXYPHEYL)TROPANE 2BETA CARBOXYLIC ACID 2 (3 BROMO 4 AMINOPHENYL)ETHYL ESTER; BENZENE DERIVATIVE; CARBOXYLIC ACID DERIVATIVE; COCAINE; DOPAMINE TRANSPORTER; ESTER DERIVATIVE; NISOXETINE; NORADRENALIN TRANSPORTER; PAROXETINE; SEROTONIN TRANSPORTER; TROPANE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; BINDING AFFINITY; DRUG DESIGN; DRUG POTENCY; DRUG PROTEIN BINDING; DRUG SCREENING; DRUG SELECTIVITY; DRUG SELF ADMINISTRATION; DRUG SYNTHESIS; IC 50; STRUCTURE ACTIVITY RELATION;

CHEMISTRY, PHARMACEUTICAL; COCAINE; DOPAMINE PLASMA MEMBRANE TRANSPORT PROTEINS; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG DESIGN; HUMANS; INHIBITORY CONCENTRATION 50; KINETICS; MAGNETIC RESONANCE SPECTROSCOPY; MODELS, CHEMICAL; NOREPINEPHRINE PLASMA MEMBRANE TRANSPORT PROTEINS; SEROTONIN PLASMA MEMBRANE TRANSPORT PROTEINS; STRUCTURE-ACTIVITY RELATIONSHIP; TEMPERATURE; TROPANES;

EID: 58149095805     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm801162z     Document Type: Article

References (35)

1. Reith, M. E. A.; Meisler, B. E.; Sershen, H.; Lajtha, A. Structural requirements for cocaine congeners to interact with dopamine and serotonin uptake sites in mouse brain and to induce stereotyped behavior. Biochem. Pharmacol. 1986, 35, 1123-1129.
2. Heikkila, R. E.; Manzino, L. Behavioral properties of GBR 12909, GBR 13069, and GBR 13098: Specific inhibitors of dopamine uptake. Eur. J. Pharmacol. 1984, 103, 241-248.
3. Bergman, J.; Madras, B. K.; Johnson, S. E.; Spealman, R. D. Effects of cocaine and related drugs in nonhuman primates. III. Self-administration by squirrel monkeys. J. Pharmacol. Exp. Ther. 1989, 251, 150-155.
4. Kuhar, M. J. Neurotransmitter transporters as drug targets: Recent research with a focus on the dopmaine transporter. Pharmacologist 1993, 35, 28-33.
5. Wise, R. A. Neural mechanisms of the reinforcing action of cocaine. NIDA Res. Monogr. 1984, 50, 15-33.
6. Ritz, M. C.; Kuhar, M. J. Relationship between self-administration of amphetamine and monoamine receptors in brain: Comparison with cocaine. J. Pharmacol. Exp. Ther. 1989, 248, 1010-1017.
7. Pierce, R. C.; Kumaresan, V. The mesolimbic dopamine system: The final common pathway for the reinforcing effect of drugs of abuse. Neurosci. Biobehav. Rev. 2006, 30, 215-238.
8. Volkow, N. D.; Wang, G.-J.; Fischman, M. W.; Foltin, R. W.; Fowler, J. S.; Abumrad, N. N.; Vitkun, S.; Logan, J.; Gatley, S. J.; Pappas, N.; Hitzemann, R.; Shea, C. E. Relationship between subjective effects of cocaine and dopamine transporter occupancy. Nature 1997, 386, 827-833.
9. Volkow, N. D.; Wang, G. J.; Fowler, J. S.; Gatley, S. J.; Logan, J.; Ding, Y. S.; Dewey, S. L.; Hitzemann, R.; Gifford, A. N.; Pappas, N. R. Blockade of striatal dopamine transporters by intravenous methylphenidate is not sufficient to induce self-reports of "High". J. Pharmacol. Exp. Ther. 1999, 288, 14-20.
10. Carroll, F. I.; Howell, L. L.; Kuhar, M. J. Pharmacotherapies for treatment of cocaine abuse: Preclinical aspects. J. Med. Chem. 1999, 42, 2721-2736.
11. Grabowski, J.; Shearer, J.; Merrill, J.; Negus, S. S. Agonist-like, replacement pharmacotherapy for stimulant abuse and dependence. Addict. Behav. 2004, 29, 1439-1464.
12. Howell, L. L.; Wilcox, K. M. The dopamine transporter and cocaine medication development: Drug self-administration in nonhuman primates. J. Pharmacol. Exp. Ther. 2001, 298, 1-6.
13. Mello, N. K.; Negus, S. S. Preclinical evaluation of pharmacotherapies for treatment of cocaine and opioid abuse using drug self-administration procedures. Neuropsychopharmacology 1996, 14, 375-424.
14. Carroll, F. I.; Pawlush, N.; Kuhar, M. J.; Pollard, G. T.; Howard, J. L. Synthesis, monoamine transporter binding properties, and behavioral pharmacology of a series of 3β-(substituted phenyl)-2β-(3′-substituted isoxazol-5-yl)tropanes. J. Med. Chem. 2004, 47, 296-302.
15. Carroll, F. I.; Howard, J. L.; Howell, L. L.; Fox, B. S.; Kuhar, M. J. Development of the dopamine transporter selective RTI-336 as a pharmacotherapy for cocaine abuse. AAPS J. 2006, 8, E196-E203.
16. Carroll, F. I.; Fox, B. S.; Kuhar, M. J.; Howard, J. L.; Pollard, G. T.; Schenk, S. Effects of dopamine transporter selective 3-phenyltropane analogs on locomotor activity, drug discrimination, and cocaine self-administration after oral administration. Eur. J. Pharmacol. 2006, 553, 149-156.
17. Runyon, S. P.; Carroll, F. I. Dopamine transporter ligands: Recent developments and therapeutic potential. Curr. Top. Med. Chem. 2006, 6, 1825-1843.
18. Runyon, S. P.; Carroll, F. I. Tropane-based dopamine transporter uptake inhibitors. In Dopamine Transporters, Chemistry, Biology and Pharmacology; Trudell, M. L., Izenwasser, S., Eds. Wiley: New York, 2007.
19. Howell, L. L.; Carroll, F. I.; Votaw, J. R.; Goodman, M. M.; Kimmel, H. L. Effects of combined dopamine and serotonin transporter inhibitors on cocaine self-administration in rhesus monkeys. J. Pharmacol. Exp. Ther. 2007, 320, 757-765.
20. 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.
21. Carroll, F. I.; Kotian, P.; Dehghani, A.; Gray, J. L.; Kuzemko, M. A.; Parham, K. A.; Abraham, P.; Lewin, A. H.; Boja, J. W.; Kuhar, M. J. Cocaine and 3β-(4′-substituted phenyl)tropane-2β-carboxylic acid ester and amide analogues. New high-affinity and selective compounds for the dopamine transporter. J. Med. Chem. 1995, 38, 379-388.
22. Lindsey, K. P.; Wilcox, K. M.; Votaw, J. R.; Goodman, M. M.; Plisson, C.; Carroll, F. I.; Rice, K. C.; Howell, L. L. Effects of dopamine transporter inhibitors on cocaine self-administration in rhesus monkeys: Relationship to transporter occupancy determined by positron emission tomography neuroimaging. J. Pharmacol. Exp. Ther. 2004, 309, 959-969.
23. Kimmel, H. L.; O'Connor, J. A.; Carroll, F. I.; Howell, L. L. Faster onset and dopamine transporter selectivity predict stimulant and reinforcing effects of cocaine analogs in squirrel monkeys. Pharmacol., Biochem. Behav. 2007, 86, 45-54.
24. Carroll, F. I.; Gao, Y.; Rahman, M. A.; Abraham, P.; Parham, K.; Lewin, A. H.; Boja, J. W.; Kuhar, M. J. Synthesis, ligand binding, QSAR, and COMFA study of 3β-(p-substituted phenyl)tropane-2β-carboxylic acid methylesters. J. Med. Chem. 1991, 34, 2719-2925.
25. Carroll, F. I.; Gao, Y.; Abraham, P.; Lewin, A. H.; Lew, R.; Patel, A.; Boja, J. W.; Kuhar, M. J. Probes for the cocaine receptor. Potentially irreversible ligands for the dopamine transporter. J. Med. Chem. 1992, 35, 1813-1817.
26. Carroll, F. I.; Abraham, P.; Lewin, A. H.; Parham, K. A.; Boja, J. W.; Kuhar, M. J. Isopropyl and phenyl esters of 3β-(4-substituted phenyl)tropan-2β-carboxylic acids. Potent and selective compounds for the dopamine transporter. J. Med. Chem. 1992, 35, 2497-2500.
27. Boja, J. W.; Rahman, M. A.; Philip, A.; Lewin, A. H.; Carroll, F. I.; Kuhar, M. J. Isothiocyanate derivatives of cocaine: Irreversible inhibition of ligand binding at the dopamine transporter. Mol. Pharmacol. 1991, 39, 339-345.
28. Carroll, F. I.; Gray, J. L.; Abraham, P.; Kuzemko, M. A.; Lewin, A. H.; Boja, J. W.; Kuhar, M. J. 3-Aryl-2-(3′-substituted-1′,2′, 4′-oxadiazol-5′-yl)tropane analogues of cocaine: Affinities at the cocaine binding site at the dopamine, serotonin, and norepinephrine transporters. J. Med. Chem. 1993, 36, 2886-2890.
29. Carroll, F. I.; Blough, B. E.; Nie, Z.; Kuhar, M. J.; Howell, L. L.; Navarro, H. A. Synthesis and monoamine transporter binding properties of 3β-(3′,4′-disubstituted phenyl)tropane-2β-carboxylic acid methyl esters. J. Med. Chem. 2005, 48, 2767-2771.
30. Carroll, F. I. 2002 Medicinal Chemistry Division Award Address: Monoamine transporters and opioid receptors. Targets for addiction therapy. J. Med. Chem. 2003, 46, 1775-1794.
31. Davies, H. M. L.; Saikali, E.; Huby, N. J. S.; Gilliat, V. J.; Matasi, J. J.; Sexton, T.; Childers, S. R. Synthesis of 2β-acyl-3β-aryl-8- azabicyclo[3.2.1]octanes and their binding affinities at dopamine and serotonin transport sites in rat striatum and frontal cortex. J. Med. Chem. 1994, 37, 1262-1268.
32. Xu, L.; Kelkar, S. V.; Lomenzo, S. A.; Izenwasser, S.; Katz, J. L.; Kline, R. H.; Trudell, M. L. Synthesis, dopamine transporter affinity, dopamine uptake inhibition, and locomotor stimulant activity of 2-substituted 3β-phenyltropane derivatives. J. Med. Chem. 1997, 40, 858-863.
33. Kozikowski, A. P.; Araldi, G. L.; Prakash, K. R.; Zhang, M.; Johnson, K. M. Synthesis and biological properties of new 2beta-alkyl- and 2beta-aryl-3-(substituted phenyl)tropane derivatives: Stereochemical effect of C-3 on affinity and selectivity for neuronal dopamine and serotonin transporters. J. Med. Chem. 1998, 41, 4973-4982.
34. Jin, C.; Navarro, H. A.; Carroll, F. I. Synthesis and receptor binding properties of 2beta-alkynyl and 2beta-(1,2,3-triazol)substituted 3beta-(substituted phenyl)tropane derivatives. Bioorg. Med. Chem. 2008, 16, 5529-5535.
35. Carroll, F. I.; Lewin, A. H.; Boja, J. W.; Kuhar, M. J. Cocaine receptor: Biochemical characterization and structure-activity relationships for the dopamine transporter. J. Med. Chem. 1992, 35, 969-981.