Interaction of cis-(6-benzhydrylpiperidin-3-yl)benzylamine analogues with monoamine transporters: Structure-activity relationship study of structurally constrained 3,6-disubstituted piperidine analogues of (2,2-diphenylethyl)-[1-(4-fluorobenzyl)piperidin-4-ylmethyl]amine

Journal of Medicinal Chemistry

Volumn 46, Issue 11, 2003, Pages 2205-2215

  Kolhatkar, Rohit B ^a   Ghorai, Sujit K ^a   George, Clifford ^b   Reith, Maarten E A ^c   Dutta, Aloke K ^a,d  

^a WAYNE STATE UNIVERSITY   (United States)

^b NAVAL RESEARCH LABORATORY   (United States)

^c UNIVERSITY OF ILLINOIS AT URBANA CHAMPAIGN   (United States)

^d Eugene Applebaum College of Pharmacy and Health Sciences   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

(2,2 DIPHENYLETHYL)[1 (4 FLUOROBENZYL)PIPERIDIN 4 YLMETHYL]AMINE; (6 BENZHYDRYLPIPERIDIN 3 YL)(1H INDOL 2 YLMETHYL)AMINE; (6 BENZHYDRYLPIPERIDIN 3 YL)(1H INDOL 3 YLMETHYL)AMINE; (6 BENZHYDRYLPIPERIDIN 3 YL)(3,4 DIFLUOROBENZYL)AMINE; (6 BENZHYDRYLPIPERIDIN 3 YL)(4 METHOXYBENZYL)AMINE; (6 BENZHYDRYLPIPERIDIN 3 YL)[2 (4 FLUOROPHENYL)ETHYL]AMINE; (6 BENZHYDRYLPIPERIDIN 3 YL)BENZO[B]THIOPHEN 3 YLMETHYLAMINE; (6 BENZHYDRYLPIPERIDIN 3 YL)BENZYLAMINE; (6 BENZHYDRYLPIPERIDIN 3 YL)THIOPHEN 2 YLMETHYLAMINE; 3BETA (4 FLUOROPHENYL) 2BETA TROPANECARBOXYLIC ACID METHYL ESTER; 4 [(6 BENZHYDRYLPIPERIDIN 3 YLAMINO)METHYL]BENZONITRILE; 4 [(6 BENZHYDRYLPIPERIDIN 3 YLAMINO)METHYL]PHENOL; BENZYL DERIVATIVE; CITALOPRAM; DOPAMINE TRANSPORTER; NISOXETINE; NORADRENALIN TRANSPORTER; PIPERIDINE DERIVATIVE; SEROTONIN TRANSPORTER; UNCLASSIFIED DRUG; VANOXERINE;

ANIMAL TISSUE; ARTICLE; BINDING AFFINITY; BRAIN; CONFORMATION; CONTROLLED STUDY; DIASTEREOISOMER; DRUG ACTIVITY; DRUG POTENCY; DRUG PROTEIN BINDING; DRUG SYNTHESIS; ENANTIOMER; NONHUMAN; RAT; STRUCTURE ACTIVITY RELATION; X RAY CRYSTALLOGRAPHY;

ANIMALS; BINDING, COMPETITIVE; BIOGENIC MONOAMINES; BIOLOGICAL TRANSPORT; BRAIN; CARRIER PROTEINS; CRYSTALLOGRAPHY, X-RAY; DOPAMINE PLASMA MEMBRANE TRANSPORT PROTEINS; MEMBRANE GLYCOPROTEINS; MEMBRANE TRANSPORT PROTEINS; MOLECULAR CONFORMATION; NERVE TISSUE PROTEINS; NITRILES; NOREPINEPHRINE PLASMA MEMBRANE TRANSPORT PROTEINS; PIPERAZINES; PIPERIDINES; RADIOLIGAND ASSAY; RATS; SEROTONIN PLASMA MEMBRANE TRANSPORT PROTEINS; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP; SYMPORTERS;

EID: 0037573222     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm020561w     Document Type: Article

References (45)

1. Musto, D. F. Opium, Cocaine and Marijuana in American History. Sci. Am. 1991, 256, 40-47.
2. Johanson, C. E.; Fischman, M. W. The Pharmacology of Cocaine Related to its Abuse. Pharmacol. Rev. 1989, 41 (1), 3-52.
3. Swan, N. Drug Abuse cost to society set at $9.7 billion, continued steady increase since 1975. NIDA Notes 1998, 13.
4. Ritz, M. C.; Cone, E. J.; Kuhar, M. J. Cocaine inhibition of ligand binding at dopamine, norpinephrine and serotonin transporters: A structure-activity study. Life Sci. 1990, 46, 635-645.
5. Ritz, M. C.; Lamb, R. J.; Goldberg, R.; Kuhar, M. J. Cocaine receptors on dopamine transporters are related to self-adminstration of cocaine. Science 1987, 237, 1219-1223.
6. Robinson, T.; Barridge, K. C. The neural basis of drug craving: An incentive-sensitization theory of addiction. Brain. Res. Rev. 1993, 18, 249-291.
7. Kuhar, M. J.; Ritz, M. C.; Boja, J. W. The dopamine hypothesis of the reinforcing properties of cocaine. Trends. Neurosci. 1991, 14, 299-302.
8. Rocha, B. A.; Fumagalli, F.; Gainetdinov, R. R.; Jones, S.; Ator, R.; Giros, B.; Miller G. W.; Caron, M. Cocaine self-administration in dopamine transporter knockout mice. Nature Neurosci. 1998, 1, 132-137.
9. Walsh, S. L.; Cunningham, K. A. Serotonergic mechanisms involved in the discrimination stimulus, reinforcing and subjective effects of cocaine. Psychopharmacology 1997, 130, 41-58.
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. Shimada, S.; Kitayama, S.; Lin, C. L.; Patel, A.; Nanthakumar, E.; Gregor, P.; Kuhar, M.; Uhl, G. Cloning and expression of a cocaine-sensitive dopamine transporter complementary DNA. Science 1991, 254, 576-578.
12. Kitayama, S.; Shimada, S.; Xu, H.; Markham, L.; Donovan, D.; Uhl, G. Dopamine transporter site-directed mutations differentially alter substrate transport and cocaine binding. Proc. Natl. Acad. Sci. 1992, 89, 7782-7785.
13. Giros, B.; Wang, Y.-M.; Suter, S.; McLeskey, S. B.; Pifl, C.; Caron, M. G. Delineation of discrete domains for substrate, cocaine and tricyclic antidepressant interactions using chimeric dopaminenorepinephrine transporters. J. Biol. Chem. 1994, 269, 15985-15988.
14. Lin, Z.; Uhl, G. R. Dopamine transporter mutants with cocaine resistance and normal dopamine uptake provide targets for cocaine antagonism. Mol. Pharmacol. 2002, 61, 885-891.
15. 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.
16. Bennett, B. A.; Wichems, C. H.; Hollingsworth, C. K.; Davies, H. M.; Thornley, C.; Sexton, T.; Childers, S. R. Novel 2-substituted cocaine analogues: Uptake and ligand binding studies at dopamine, serotonin and norepinephrine transport sites in the rat brain. J. Pharmacol. Exp. Ther. 1995, 272, 1176-1186.
17. 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.
18. Zhang, C.; 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. 1998, 41, 2430-2435.
19. Kozikowski, A. P.; Araldi, G. L.; Boja, J.; Meil, W. M.; Johnson, K. M.; Flippen-Anderson, J. L.; George, C.; Saiah, E. Chemistry and Pharmacology of the Piperidine-Based Analogues of Cocaine. Identification of Potent DAT Inhibitors Lacking the Tropane Skeleton. J. Med. Chem. 1998, 41, 1962-1969.
20. Agoston, G. E.; Wu, J. H.; Izenwasser, S.; George, C.; Katz, J.; Kline, R. H.; Newman, A.-H. Novel N-substituted 3a-[bis(4′-fluorophenyl)methoxy]tropane analogues: selective ligands for the dopamine transporter. J. Med. Chem. 1997, 40, 4329-4339.
21. 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.
22. Aeberli, P.; Eden, P.; Gogerty, J. H.; Houlihan, W. J.; Penberthy, C. 5-Aryl-2,3-dihydro-5H-imidazole[2,1-a]isoindol-5-ols. A novel class of anorectic agents. J. Med. Chem. 1975, 18, 177-182.
23. 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.
24. Matecka, D.; Lewis, D.; Rothman, R. B.; Dersch, C. M.; Wojnicki, F. H. E.; Glowa, J. R.; DeVries, C.; Pert, A.; Rice, K. C. Heteroaromatic analogues of 1-[2-(diphenylmethoxy)ethyl]- and 1-[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.
25. Carrol, F. I.; Lewin, A. H.; Mascarella, S. W. Dopamine transporter uptake blockers: Structure activity relationships. In Neurotransmitter Transporters: Structure and Function, 2nd ed.; Reith, M. E. A., Eds.; Human Press: Totowa, NJ, 2002; pp 381-432.
26. Singh, S. Chemistry, design, and structure-activity relationship of cocaine antagonists. Chem. Rev. 2000, 100, 925-1024.
27. Dutta, A. K.; Xu, C.; Reith, M. E. A. Structure-Activity Relationship Studies of Novel 4-[2-[Bis(4-fluorophenyl)methoxy]- ethyl]-1-(3-phenylpropyl)piperidine Analogues: Synthesis and Biological Evaluation at the Dopamine and Serotonin Transporter Sites. J. Med. Chem. 1996, 39, 749-756.
28. Dutta, A. K.; Coffey, L. L.; Reith, M. E. A. Highly selective, novel analogues of 4-[2-(diphenylmethoxy)ethyl]-1-benzylpiperidine for the dopamine transporter: Effect of different aromatic substitutions on their affinity and selectivity. J. Med. Chem. 1997, 40, 35-43.
29. Dutta, A. K.; Coffey, L. L.; Reith, M. E. A. Potent and selective ligands for the dopamine transporter (DAT): Structure-activity relationship studies of novel 4-[2-(diphenylmethoxy)ethyl]-1-(3-phenylpropyl)piperidine analogues. J. Med. Chem. 1998, 41, 699-705.
30. Dutta, A. K.; Fei, X.-S.; Beardsley, P.; Newman, J.; Reith, M. E. A. Structure-Activity Relationship Studies of 4-[2-(Diphenylmethoxy)-ethyl]-1-benzylpiperidine Derivatives and their N-analogues: Evaluation of Behavioral Activity of O-and N-Analogues and their Binding to Monoamine transporters. J. Med. Chem. 2001, 44, 937-948.
31. Dutta, A. K.; Davis, M.; Fei X-S.; Beardsley, P. M.; Cook, C. D.; Reith M. E. A. Expansion of Structure-Activity Studies in piperidine analogues of 1-[2-(diphenylmethoxy)ethyl]-4-(3- phenylpropyl)piperazine (GBR 12935) compounds by altering substitutions in the N-benzyl moiety and behavioral pharmacology of selected molecules. J. Med. Chem. 2002, 45, 654-662.
32. Koshland, D. E. Biological specificity in protein small molecule interactions. Biochem. Pharmacol. 1961, 8, 57.
33. (a) Hruby, V. J. Conformational restrictions ofbiologically active peptides via amino acid side chain groups. Life Sci. 1982, 31, 189-199.
34. (b) Avbelj, F.; Hadzi, D. Potential energy functions and the role of the conformational entropy of clonidine-like imidazolidines in determining their affinity for a-adrenergic receptors. Mol. Pharmacol. 1985, 27, 466-470.
35. Schiller, P. W.; Weltrowska, G.; Nguyen, T. M.; Wilkes, B. C.; Chung, N. N.; Lemieux, C. Conformationally restricted deltorphin analogues. J. Med. Chem. 1992, 35, 3956-3961.
36. Dutta, A. K.; Davis, M. C.; Reith, M. E. A. Rational Design and synthesis of novel conformationally constrained 2,5-disubstituted cis- and trans-piperidine derivatives exhibiting differential activity for the dopamine transporter. Bioorg. Med. Lett. 2001, 11, 2337-2340.
37. Makosza, M.; Wojciechowski, K.; Jawdosiuk M. Reactions of organic anions. Part LXXIX. Aromatic nucleophilic substitution in chloronitrobenzenes by carbinols derived from N-substituted oxindoles. Pol. J. Chem. 1978, 52, 1173-1178.
38. Sury, E.; Hoffmann, K. Helv. Chem. Acta 1954, 247-248, 2133-214.
39. Basha.; Lipton, M.; Weinreb, M. A mild general method for conversion of esters to amides. Tetrahedron Lett. 1977, 48, 4171-4174.
40. (a) Wikstrom, H.; Sanchez, D.; Lindberg, P.; Hacksell, U.; Arvidsson, L.-E.; Johansson, A. M.; Thorberg, S.-O.; Nilsson, J.; Svensson, K.; Hjorth, S.; Clark, D.; Carlsson, A. Resolved 3-(3- hydroxyphenyl)-N-n-propylpiperidine and its analogues: Central dopamine receptor activity. J. Med. Chem. 1984, 27, 1030-1036.
41. (b) Brozda, D.; Koroniak, L.; Rozwadowska, M. Stereo-selective synthesis of 3-mono- and 1,3-disubstituted 4-phenyl-1, 2, 3, 4-tetrahydroisoquinolines. Tetrahedron: Asymmetry 2000, 11, 3017-3025.
42. Handbook of Heterocyclic Chemistry, 2nd ed.; Katritzky, A. R., Pozharskii, A. F., Eds.; Pergamon Press: New York, 2000.
43. Vaughan, R. A.; Gaffaney, J. D.; Lever, J. R.; Reith, M. E. A.; Dutta. Dual Incorporation of Photoaffinity Ligands on Dopamine Transporters Implicates Proximity of Labeled Domains. Mol. Pharmacol. 2001, 59, 1157-1164.
44. Bruker 1995 SMART and SAINT Data Collection and Reduction Software for the SMART system. Bruker-AXS, Madison, WI.
45. Sheldrick, G. M. SHELXTL Version 5.1 Bruker Analytical X-ray Instruments, Madison, WI, 1997.