Synthesis and pharmacology of site-specific cocaine abuse treatment agents: 2-(Aminomethyl)-3-phenylbicyclo [2.2.2]- and - [2.2.1] alkane dopamine uptake inhibitors

Journal of Medicinal Chemistry

Volumn 42, Issue 5, 1999, Pages 882-895

  Deutsch, Howard M ^a   Collard, David M ^a   Zhang, Liang ^a   Burnham, Kikue S ^a   Deshpande, Abhay K ^a   Holtzman, Stephan G ^b   Schweri, Margaret M ^c  

^a GEORGIA INSTITUTE OF TECHNOLOGY   (United States)

^b EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c MERCER UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 [2 (BENZHYDRYLOXY)ETHYL] 4 (3 PHENYLALLYL)PIPERAZINE; 3BETA (4 FLUOROPHENYL) 2BETA TROPANECARBOXYLIC ACID METHYL ESTER; ALKANE DERIVATIVE; DOPAMINE; DOPAMINE UPTAKE INHIBITOR; METHYLPHENIDATE; TROPARIL;

ARTICLE; COCAINE DEPENDENCE; DOSE RESPONSE; DRUG BINDING; DRUG BINDING SITE; DRUG DEPENDENCE TREATMENT; DRUG DISCRIMINATION; DRUG INHIBITION; DRUG POTENCY; DRUG SYNTHESIS; DRUG UPTAKE; NONHUMAN; PHARMACOPHORE; RAT; STRUCTURE ACTIVITY RELATION;

ANIMALS; BICYCLO COMPOUNDS; COCAINE; COCAINE-RELATED DISORDERS; DISCRIMINATION LEARNING; DOPAMINE; DOPAMINE UPTAKE INHIBITORS; MALE; MODELS, MOLECULAR; NEOSTRIATUM; PROTEIN BINDING; RATS; RATS, SPRAGUE-DAWLEY; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP; SYNAPTOSOMES;

EID: 0033545578     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm980566m     Document Type: Article

References (53)

1. Rouse, B. A. Trends in cocaine use in the general population. NADA Res. Monogr. 1991, 110, 5-18. Also see: Rouse, B. A. Trends in cocaine use in the general population. Subst. Use Misuse 1997, 32, 1721-1726.
2. Rouse, B. A. Trends in cocaine use in the general population. NADA Res. Monogr. 1991, 110, 5-18. Also see: Rouse, B. A. Trends in cocaine use in the general population. Subst. Use Misuse 1997, 32, 1721-1726.
3. National Household Survey on Drug Abuse: Population Estimates 1990. DHSS Pub. No. (AM) 91-1732; Washington, DC, 1991; pp 29-39, 59-63, 111-115.
4. National Household Survey on Drug Abuse: Population Estimates 1990. DHSS Pub. No. (AM) 91-1732; Washington, DC, 1991; pp 29-39, 59-63, 111-115.
5. 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.
6. 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, 219, 150-155.
7. Kuhar, M. J.; Ritz, M. C.; Boja, J. W. The dopamine hypothesis of the reinforcing properties of cocaine. Trends Anuresis 1991, 14, 299-302.
8. Rocha, B. A.; Scearce-Levie, K.; Lucas, J. J.; Hiroi, N.; Castanon, N.; Crabbe, J. C.; Nestler, E. J.; Hen, R. Increased vulnerability to cocaine in mice lacking the serotonin-1B receptor. Nature 1998, 393, 175-178.
9. Walsh, S. L.; Cunningham, K. A. Serotonergic mechanisms involved in the discriminative stimulus, reinforcing and subjective effects of cocaine. Psychopharmacology 1997, 130, 41-58.
10. Keverline-Franz, K. I.; Boja, J. W.; Kuhar, M. J.; Abraham, P.; Burgess, J. P.; Legin, A. H.; Carroll, F. I. Synthesis and ligand binding of propane ring analogues of paroxetine. J. Med. Chem. 1998, 41, 247-257.
11. (a) Rothman, R. D. High affinity dopamine reuptake inhibitors as potential cocaine antagonists: a strategy for drug development. Life Sci. 1990, 46, PL217-PL221.
12. (b) Rothman, R. D.; Male, A.; Reid, A. A.; Aachen, H.; Greg, N.; Thurkauf, A.; Rice, K. C.; Pert, A. Tight binding dopamine reuptake inhibitors as cocaine antagonists. A strategy for drug development. FEB. Lett. 1989, 257, 241-244.
13. Rothman, R. D.; Glowa, J. R. A review of the effects of dopaminergic agents on humans, animals, and drug-seeking behavior, and its implications for medication development - Focus on GB 12909. Mol. Neurobiol. 1995, 11, 1-19.
14. (a) Glowa, J. R.; Wojnicki, F. H. E.; Matecka, D.; Bacher, J.; Mansbach, R. S.; Balster, R. L.; Rice, K. C. Effects of dopamine reuptake inhibitors on food- and cocaine-maintained responding. I: Dependence of unit dose of cocaine. Exp. Clin. Psycopharmcol. 1995, 3, 219-231.
15. (b) Glowa, J. R.; Wojnicki, F. H. E.; Matecka, D.; Rice, K. C.; Rothman, R. B. Effects of dopamine reuptake inhibitors on food- and cocaine-maintained responding. II: Comparisons with other drugs and repeated administrations. Exp. Clin. Psycopharmcol. 1995, 3, 232-239.
16. Koetzner, L.; Riley, A. L.; Glowa, J. R. Discriminative stimulus effects of dopaminergic agents in rhesus monkeys. Pharmacol. Biochem. Behav. 1996, 54, 517-523.
17. Grabowski, J.; Roache, J. D.; Schmitz, J. M.; Rhoades, H.; Creson, D.; Korszun, A. Replacement medication for cocaine dependence: Methylphenidate. J. Clin. Psychopharmacol. 1997, 17, 485-488.
18. Deutsch, H. M.; Shi, Q.; Gruszecka-Kowalik, E.; Schweri, M. M. Synthesis and pharmacology of potential cocaine antagonists. 2. Structure-activity relationship studies of aromatic ring-substituted methylphenidate analogues. J. Med. Chem. 1996, 39, 1201-1209.
19. Deutsch, H. M.; Schweri, M. M. Can stimulant binding and dopamine transport be differentiated? Studies with GBR 12783 derivatives. Life Sci. 1994, 55, PL115-PL120.
20. Deutsch, H. M.; Schweri, M. M.; Culbertson, C. T.; Zalkow, L. H. Synthesis and pharmacology of irreversible affinity labels as potential cocaine antagonist: aryl 1,4-dialkylpiperazines related to GBR-12783. Eur. J. Pharmacol. 1992, 220, 173-180.
21. Katoomba, S.; Doh, T. Cellular and molecular aspects of monoamine neurotransmitter transporters. Jpn. J. Pharmacol. 1996, 72, 195-208.
22. Carroll, F. I.; Lewin, A. H.; Kuhar, M. J. Dopamine Transporter Uptake Blockers. Structure-Activity Relationships. In Neurotransmitter Transporters: Structure, Function and Regulation; Reith, M. E. A., Eds.; Humana Press: Totowa, 1996; 263-295.
23. Cashin, C. H.; Fairhurst, J.; Horwell, D. C.; Pullar, I. A.; Sutton, S.; Timms, G. H.; Wildsmith, E.; Wright, F. Potential anti-depressant and C.N.S. stimulant activity in a series of cis and trans fused 3-aminomethyl-2-phenylbicyclo[2,2,2]octane and analogous oct-2-ene derivatives. Eur. J. Med. Chem. - Chim. Ther. 1978, 13 (6), 495-501.
24. Wedley, S.; Howard, J. L.; Lange, B. T.; Pullar, I. A. The inhibition of monoamine uptake into rat brain synaptosomes by selected bicyclo-octanes and an analogous bicyclo-octene. Biochem. Pharmacol. 1978, 27, 2907-2909.
25. Wong, D. T.; Bymaster, F. P. An inhibitor of dopamine uptake, LR5182, cis-3-(3,4-dichlorophenyl)-2-N,N-dimethylaminomethyl-bicyclo[2,2,2]octane, hydrochloride. Life Sci. 1978, 23, 1041-1048.
26. Wong, D. T.; Bymaster, F. P.; Reid, L. R. Competitive inhibition of catecholamine uptake in synaptosomes of rat brain by rigid bicyclo-octanes. J. Neurochem. 1980, 34 (6), 1453-1458.
27. Poos, G. I.; Kleis, J.; Wittekind, R. R.; Rosenau, J. D. Bicyclic bases. III. Isomeric 2-amino-3-phenylnorbornanes. J. Org. Chem. 1961, 26, 4898-4904.
28. Fairhurst, J.; Horwell, D. C.; Timms, G. H. A snythesis of cis-α,β-unsaturated nitriles by kinetically controlled decarboxylation. Tetrahedron Lett. 1975, 44, 3843-3844.
29. Nicolas, L.; Beugelmans-Verrier, M. Interaction entre groupes aromatique et polaire voisins - III. Synthesis et etudes physicochimiques d'acides p-X-phenyl-3-bicyclo[2.2.1]heptane-5-carboxyliques-2 et de leurs esters methyliques. Tetrahedron 1981, 37, 3847-3860.
30. 3H]DA-uptake-inhibition to transporter-binding-inhibition ratios for the in vitro evaluation of putative cocaine antagonists. Life Sci. 1993, 53, PL267-PL272.
31. Xu, C.; Coffey, L. L.; Reith, M. E. A. Translocation of dopamine and binding of 2-β-carbomethoxy-3-β-(4-fluorophenyl) tropane (WIN 35,428) measured under identical conditions in rat striatal synaptosomal preparations. Biochem. Pharmcol. 1995, 49, 339-350.
32. 50-DA + [I]) and setting this to 0.10 (10% inhibition) predicts a DR of 36.
33. Froimowitz, M.; Deutsch, H. M.; Shi, Q.; Wu, K. M.; Glaser, R.; Adin, I.; George, C.; Schweri, M. M. Further evidence for a dopamine reuptake pharmacophore. The effect of N-methylation on threo-methylphenidate and its analogues. Bioorg. Med. Chem. Lett. 1997, 7, 1213-1218.
34. Zhang, C. M.; Izenwasser, S.; Katz, J. L.; Terry, P. D.; Trudell, M. L. Synthesis and dopamine transporter affinity of the four stereoisomers of (±)-2-(methoxycarbonyl)-7-methyl-3-phenyl-7-azabicyclo[2.2.1]heptane. J. Med. Chem. 1998, 41, 2430-2435.
35. Froimowitz, M. Conformational analysis of cocaine, the potent analogue 2b-carbomethoxy-3-(4-fluorophenyl)tropane (CFT), and other dopamine reuptake blocker. J. Comput. Chem. 1993, 14, 934-943.
36. CS ChemOffice Ultra Version 4.0, Cambridge Soft Corp., Cambridge, MA.
37. Lieske, S. F.; Yang, B.; Eldefrawi, M. E.; MacKerell, A. D., Jr.; Wright, J. (-)-3b-substituted ecgonine methyl esters as inhibitors for cocaine binding and dopamine uptake. J. Med. Chem. 1998, 41, 864-876.
38. Meltzer, P. C.; Liang, A. Y.; Blundell, P.; Gonzalez, M. D.; Chen, Z. M.; 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.
39. Kozikowski, A. P.; Saiah, M. K. E.; Bergmann, J. S.; Johnson, K. M. Structure-activity relationship studies of N-sulfonyl analogues of cocaine: Role of ionic interaction in cocaine binding. J. Med. Chem. 1994, 37, 3440-3442.
40. Meltzer, P. C.; Blundell, P.; Madras, B. K. Structure activity relationships of inhibition of the dopamine transporter by 3-arylbicyclo[3.2.1]octanes. Med. Chem. Res. 1998, 8, 12-34.
41. 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)-, and 3β-(3',4'-disubstituted phenyl)tropane-2β-carboxylic acid methyl esters. J. Med. Chem. 1994, 37, 2865-2873.
42. (a) Carroll, F. I.; Lewin, A. H.; Kuhar, M. J. 3β-phenyl-2β-substituted tropanes -An SAR analysis. Med. Chem. Res. 1998, 8, 59-65.
43. (b) Lewin, A. H.; Gao, Y.; Abraham, P.; Boja, J. W.; Kuhar, M. J.; Carroll, F. I. 2β-Substituted analogues of cocaine. Synthesis and inhibition of binding to the cocaine receptor. J. Med. Chem. 1992, 35, 135-140.
44. Lapworth, A.; Baker, W. α-Cyano-β-phenylacrylic acid. Organic Synthesis; Wiley: New York, 1941; Collect. Vol. 1, pp 181-183.
45. Fiquet, E. Aromatiques avec l'acide cyanacetique. (Aromatics with cyanoacetic acid.) Ann. Chem. (Paris) 1939, 29, 472-504.
46. Butt, G.; Topsom, R. D. Carbon-13 substituent chemical shifts of 4-substituted bicyclo[2.2.2]oct-1-yl cyanides. Spectrochim. Acta, Part A 1982, 38, 301-306.
47. Dinwiddie, J. G.; McManus, S. P. Bicyclic Ketones. I. Reaction of Cyclopentadiene with cis- and trans-Benzalactone and Acetylphenylacetylene. J. Org. Chem. 1963, 28, 2416-2419.
48. a. Tetrahedron Lett. 1976, 361-364.
49. Alder, K.; Gunzl, W. Uber den sterischen verlaut der additionen von α-und β-methyl-bzw.-phenyl-substituierten acryl suren an cyclopendien ein beitrag stereochemie der dien-synthese. Chem. Ber. 1960, 93, 809-825.
50. Reith, M. E. A.; Selmeci, G. Radiolabeling of dopamine uptake sites for cocaine, mazindol, and GBR 12935. Naunyn-Schmied. Arch. Pharmacol. 1992, 345, 309-318.
51. 3H]-methylphenidate, a proposed marker for the dopamine transport complex. Life Sci. 1989, 45, 1689-1698.
52. Woolverton, W. L. Discriminative stimulus effects of cocaine. In Drug Discrimination: Applications to Drug Abuse Research; Glennon, R. A., Jarbe, T. U. C., Frankenheim, J., Eds.; U.S. Department of Health and Human Resources Publication No. (ADM) 92-1878; 1991; pp 61-74.
53. Shannon, H. E.; Holtzman, S. G. Evaluation of the discriminative effects of morphine in the rat J. Pharmacol. Exp. Ther. 1976, 198, 54-65.