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

Journal of Medicinal Chemistry

Volumn 39, Issue 2, 1996, Pages 371-379

  Meltzer, Peter C ^a   Liang, Anna Y ^a   Madras, Bertha K ^b  

^a ORGANIX INC   (United States)

^b HARVARD MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

3ALPHA (4,4' DIFLUOROBENZHYDRYLOXY) 2BETA TROPANECARBOXYLIC ACID METHYL ESTER; 3ALPHA (4,4' DIFLUOROBENZHYDRYLOXY) N (3 PHENYLPROPYL) 2BETA NORTROPANECARBOXYLIC ACID METHYL ESTER; 3ALPHA (4,4' DIFLUOROBENZHYDRYLOXY) N (5 PHENYLPENTYL) 2BETA NORTROPANECARBOXYLIC ACID METHYL ESTER; 3ALPHA (4,4' DIFLUOROBENZHYDRYLOXY) N [3 (4 IODOPHENYL)PROPYL] 2BETA NORTROPANECARBOXYLIC ACID METHYL ESTER; 3BETA (4 FLUOROPHENYL) 2BETA TROPANECARBOXYLIC ACID METHYL ESTER; CITALOPRAM; COCAINE; DOPAMINE RECEPTOR; N [3 (4 BROMOPHENYL)PROPYL] 3ALPHA (4,4' DIFLUOROBENZHYDRYLOXY) 2BETA NORTROPANECARBOXYLIC ACID METHYL ESTER; N BENZYL 3ALPHA (4,4' DIFLUOROBENZHYDRYLOXY) 2BETA NORTROPANECARBOXYLIC ACID METHYL ESTER; O 747; O 755; O 764; O 786; O 788; TROPANE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; BINDING AFFINITY; DOPAMINERGIC SYSTEM; DRUG BINDING; DRUG POTENCY; STRUCTURE ACTIVITY RELATION;

ANIMALS; BENZTROPINE; BINDING SITES; BRAIN; CARRIER PROTEINS; DOPAMINE; DOPAMINE AGENTS; DOPAMINE PLASMA MEMBRANE TRANSPORT PROTEINS; FEMALE; MACACA FASCICULARIS; MALE; MEMBRANE GLYCOPROTEINS; MEMBRANE TRANSPORT PROTEINS; NERVE TISSUE PROTEINS; PIPERAZINES; SEROTONIN; SEROTONIN PLASMA MEMBRANE TRANSPORT PROTEINS;

EID: 0030051988     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm950463t     Document Type: Article

References (31)

1. Kennedy, L. T.; Hanbauer, I. Sodium sensitive cocaine binding to rat striatal membrane: possible relationship to dopamine uptake sites. J. Neurochem. 1983, 34, 1137-1144.
2. 3H]cocaine binding associated with dopamine uptake sites in the rat striatum and human putamen decrease after dopaminergic denervation and in Parkinson's disease. Naunyn-Schmiedeberg's Arch. Pharmacol. 1985, 325, 227-235.
3. 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.
4. 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.
5. 3H]Cocaine binding sites in caudate-putamen. J. Pharmacol. Exp. Ther. 1989, 251, 131-141.
6. 3H]2β-Carbomethoxy-3β(4-fluorophenyl)tropane. Mol. Pharmacol. 1989, 36, 518-524.
7. 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.
8. 3H]WIN 35,428) in the monkey brain. Synapse 1990, 6, 189-195.
9. Kaufman, M. J.; Madras, B. K. Severe depletion of cocaine recognition sites associated with the dopamine transporter in Parkinson's diseased striatum. Synapse 1991, 9, 43-49.
10. Kuhar, M. J.; Ritz, M. C.; Boja, J. W. The dopamine hypothesis of the reinforcing properties of cocaine. Trends Neurosci. 1991, 14, 299-302-
11. 3H]cocaine receptors. Pharmacol. Biochem. Behav. 1990, 35, 949-953.
12. 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 methyl esters. J. Med. Chem. 1991, 34, 2719-2725.
13. Carroll, F. I.; Mascarella, S. W.; Kuzemko, M. A.; Gao, Y.; Abraham, P.; Lewin, A. H.; Boja, J. W.; Kuhar, M. J. Synthesis, Ligand Binding, and QSAR (CoMFA and Classical) Study of 3β-(3′-Substituted phenyl)-, 3β-(4′-Substituted phenyl)-, 3,β(3′,4′-Disubstituted phenyl)tropane-2β-carboxylic Acid Methyl Esters. J. Med. Chem. 1994, 37, 2865-2873.
14. Meltzer, P. C.; Liang, A. Y.; Brownell, A.-L.; Elmaleh, D. R.; Madras, B. K. 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.
15. Carroll, F. I.; Lewin, A. H.; Boja, J. W.; Kuhar, M. J. Cocaine Receptor: Biochemical Characterization and Structure Activity Relationships of Cocaine Analogues at the Dopamine Transporter. J. Med. Chem. 1992, 35, 969-981.
16. Carroll, F. I.; Abraham, P.; Lewin, A.; Parham, K. A.; Boja, J. W.; Kuhar, M. J. Isopropyl and phenyl esters of 3β-(4-substituted phenyl) tropane-2β-carboxylic acids. Potent and selective compounds for the dopamine transporter. J. Med. Chem. 1992, 35, 2497-2500
17. Boja, J. W.; McNeill, R. M.; Lewin, A.; Abraham, P.; Carroll, F. I.; Kuhar, M. J. Selective dopamine transporter inhibition by cocaine analogs. Mol. Neurosci. 1992, 3, 984-986.
18. Davies, H. M. L.; Saikali, E.; Sexton, T.; Childers, S. R. Novel 2-substituted cocaine analogs: binding properties at dopamine transport sites in rat striatum. Eur. J. Pharmacol. Mol. Pharmacol. 1993, 244, 93-97.
19. Kozikowski, A. P.; Roberti, M.; Xiang, L.; Bergmann, J. S.; Callahan, P. M.; Cunningham, K. A.; Johnson, K. M. Structure-activity relationship studies of cocaine: replacement of the C-2 ester group by vinyl argues against H-bonding and provides an esterase-resistant, high-affinity cocaine analogue. J. Med. Chem. 1992, 35, 4764-4766.
20. Kozikowski, A. P.; Roberti, M.; Johnson, K. M.; Bergmann, J. S.; Ball, R. G. SAR of Cocaine: further exploration of structural variations at the C-2 center provides compounds of subnanomolar binding potency. Bioorg. Med. Chem. Lett. 1993, 3, 1327-1332.
21. Kitayama, S.; Shimada, S.; Xu, H.; Markham, L.; Donovan, D. H.; Uhl, G. R. Dopamine transporter site-directed mutations differentially alter substrate transport and cocaine binding. Proc. Natl. Acad. Sci. U.S.A. 1993, 89, 7782-7785.
22. 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 in cocaine binding. J. Med. Chem. 1994, 37, 3440-3442.
23. 125I]-2β-carbomethoxy-3β-(4-fluorophenyl)-N-(iodoprop-1-en- 3-yl)nortropane (Altropane): A selective SPECT agent for imaging DA reuptake sites. J. Nucl. Chem. 1995, accepted for publication.
24. Goodman, M. M.; Kung, M.-P.; Kabalka, G. W.; Kung, H. F.; Switzer, R. Synthesis and characterization of radioiodinated N-(3-iodopropen-1-yl)2β-carbomethoxy-3β-(4-chlorophenyl)tropanes: Potential dopamine reuptake site imaging agents. J. Med Chem. 1994, 37, 1535-1542.
25. Meltzer, P. C.; Liang, A. Y.; Madras, B. K. The discovery of an unusually selective and novel cocaine analog: Difluoropine. Synthesis and inhibition of binding at cocaine recognition sites. J. Med. Chem. 1994, 37, 2001-2010.
26. 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. 1980, 15, 363-370.
27. 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.
28. Dutta, A. K.; Meltzer, P. C.; Madras, B. K. Positional importance of the nitrogen atom in novel piperidine analogs of GBR 12909: Affinity and selectivity for the dopamine transporter. Med. Chem. Res. 1993, 3, 209-222.
29. Madras, B. K.; Reith, M. E. A.; Meltzer, P. C.; Dutta, A. K. O-526, a piperidine analog of GBR 12909, retains high affinity for the dopamine transporter in monkey caudate putamen. Eur. J. Pharmacol. 1994, 267, 167-173.
30. 3H]GBR 12935 binding in vitro to rat striatal membranes: Labeling of the dopamine uptake complex. J. Neurochem. 1987, 48, 1887-1896.
31. Andersen, P. H. The dopamine uptake inhibitor GBR 12909: selectivity and molecular mechanism of action. Eur. J. Pharmacol. 1989, 166, 493-504.