Synthesis, ligand binding, and quantitative structure-activity relationship study of 3β-(4'-substituted phenyl)-2β-heterocyclic tropanes: Evidence for an electrostatic interaction at the 2β-position

Journal of Medicinal Chemistry

Volumn 39, Issue 14, 1996, Pages 2753-2763

  Kotian, Pravin ^a   Mascarella, S Wayne ^a   Abraham, Philip ^a   Lewin, Anita H ^a   Boja, John W ^b   Kuhar, Michael J ^b   Carroll, F Ivy ^a  

^a RTI INTERNATIONAL   (United States)

^b NIDA Addiction Research Center   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DOPAMINE; DOPAMINE RECEPTOR; TROPANE DERIVATIVE;

ARTICLE; BINDING SITE; CALCULATION; DOPAMINERGIC TRANSMISSION; DRUG SYNTHESIS; DRUG TRANSPORT; LIGAND BINDING; SEROTONIN BLOOD LEVEL; STRUCTURE ACTIVITY RELATION;

ANIMALS; BINDING SITES; BINDING, COMPETITIVE; CARRIER PROTEINS; COCAINE; DOPAMINE PLASMA MEMBRANE TRANSPORT PROTEINS; LIGANDS; MEMBRANE GLYCOPROTEINS; MEMBRANE TRANSPORT PROTEINS; MODELS, MOLECULAR; NERVE TISSUE PROTEINS; RATS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0029899173     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm960160e     Document Type: Article

References (34)

1. Fischman, M. W.; Schuster, C. R. Cocaine self administration in humans. Fed. Proc. 1988, 41, 241-246.
2. Johanson, C. E.; Fischman, M. W. The pharmacology of cocaine related to its abuse. Pharmacol. Rev. 1989, 41, 3-52.
3. Koob, G. F.; Bloom, F. E. Cellular and molecular mechanisms of drug dependence. Science 1988, 242, 715-723.
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. 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.
6. Carroll, F. I.; Abraham, P.; Kuzemko, M. A.; Gray, J. L.; Lewin, A. H.; Boja, J.W.; Kuhar, M. J. Synthesis and cocaine receptor affinities of 3-phenyl-2-(3′-methyl-1,2,4-oxadiazole-5′-yl)tropane Isomers. J. Chem. Soc., Chem. Commun. 1993, 44-46.
7. 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 (20), 2886-2890.
8. 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.
9. Kotian, P.; Abraham, P.; Lewin, A. H.; Mascarella, S. W.; Boja, J. W.; Kuhar, M. J.; Carroll, F. I. Synthesis and ligand binding study of 3β-(4′-substituted phenyl)-2β-(heterocyclic)tropanes. J. Med. Chem. 1995, 38 (18), 3451-3453.
10. Carroll, F. I.; Lewin, A. H.; Kuhar, M. J. Dopamine Transporter Uptake Blockers: Structure Activity Relationships. In Neurotransmitter Transporters: Structure and Function; Reith, M. E. A., Eds.; Human Press Publishers: Totowa, NJ, in press.
11. Carroll, F. I.; Gao, Y.; Rahman, M. A.; Abraham, P.; Lewin, A. H.; Boja, J. W.; Kuhar, M. J. Synthesis, ligand binding, QSAR, and CoMFA study of 3β-(p-substituted phenyl)tropan-2β-carboxylic acid methyl esters. J. Med. Chem. 1991, 34, 2719-2927.
12. 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.
13. Saunders, J.; Cassidy, M.; Freedman, S. B.; Harley, E. A.; Iversen, L. L.; Kneen, C.; MacLeod, A. M.; Merchant, K. J.; Snow, R. J.; Baker, R. Novel quinuclidine-based ligands for the muscarinic cholinergic receptor. J. Med. Chem. 1990, 35, 1128-1138.
14. Afanasiadi, L. S.; Tur, I. N.; Kurapov, P. B. Chem. Heterocycl. Compd. 1985, 397-400.
15. El-Barbary, A. A.; Scheibyl, S.; Lawesson, S. O.; Fritz, H. Acta Chem. Scand. 1980, 597-601.
16. 50) of an enzyme reaction. Biochem. Pharmacol. 1973, 22, 3099-3108.
17. Burger, A. Isosterism and bioisosterism in drug design. Prog. Drug Res. 1991, 37, 287-371.
18. Boja, J. W.; McNeill, R. M.; Lewin, A. H.; Abraham, P.; Carroll, F. I.; Kuhar, M. J. Selective dopamine transporter inhibition by cocaine analogs. NeuroReport 1992, 3 (11), 984-986.
19. 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.
20. Carroll, F. I.; Kotian, P.; Gray, J. L.; Abraham, P.; Kuzemko, M, A.; Lewin, A. H,; Boja, J. W.; Kuhar, M. J. 3β-(4′-Chlorophenyl)tropan-2β-carboxamides and cocaine amide analogues: new high affinity and selective compounds for the dopamine transporter. Med. Chem. Res. 1993, 3, 468-472.
21. Kelkar, S. V.; Izenwasser, S.; Katz, J. L.; Klein, C. L.; Zhu, N.; Trudell, M. L. Synthesis, cocaine receptor affinity, and dopamine uptake inhibition of several new 2β-substituted 3β-phenyltropanes. J. Med. Chem. 1994, 37, 3875-3877.
22. 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.
23. Kozikowski, A. P.; Saiah, M. K. E.; Johnson, K. M.; Bergmann, J. S. Chemistry and biology of the 2β-alkyl-3β-phenyl analogues of cocaine: Subnanomolar affinity ligands that suggest a new pharmacophore model at the C-2 position. J. Med. Chem. 1995, 38, 3086-3093.
24. Spartan 3.1, 1994; Wavefunction, Inc., 18401 Von Karman Ave., Suite 370, Irvine, CA 92715.
25. Luque, F. J.; Illas, F.; Orozco, M. Comparative study of the molecular electrostatic potential obtained from different wave-functions. Reliability of the semiempirical MNDO wavefunction. J. Comput. Chem. 1990, 11 (4), 416-430.
26. Rodriguez, J.; Manaut, F.; Sanz, F. Quantitative comparison of molecular electrostatic potential distributions from several semiempirical and ab initio wave functions. J. Comput. Chem. 1993, 14 (8), 922-927.
27. Finn, P. W. The Calculation, Representation and Analysis of Molecular Fields. In Molecular Modelling and Drug Design; Vinter, J. G., Gardner, M., Eds.; CRC Press: Boca Raton, FL, 1994; pp 266-304.
28. Wadsworth, H. J.; Jenkins, S. M.; Orlek, B. S.; Cassidy, F.; Clark, M. S. G.; Brown, F.; Riley, G. J.; Graves, D.; Hawkins, J.; Naylor, C. B. Synthesis and muscarinic activities of quinuclidin-3-yltriazole and -tetrazole derivatives. J. Med. Chem. 1992, 35, 1280-1290.
29. +. J. Am. Chem. Soc. 1975, 97 (3), 955-965.
30. Murray, J. S.; Ranganathan, S.; Politzer, P. Correlations between the solvent hydrogen bond acceptor parameter β and the calculated molecular electrostatic potential. J. Org. Chem. 1991, 56, 3734-3737.
31. MacLeod, A. M.; Baker, R.; Freedman, S. B.; Patel, S.; Merchant, K. J.; Roe, M.; Saunders, J. Synthesis and muscarinic activities of 1,2,4-thiadiazoles. J. Med. Chem. 1990, 33, 2052-2059.
32. Fang, J.-Y.; Thomson, C. Hydrogen-bonding effects, electrostatic potential, and the antitumor activity of flavone acetic acid and related compounds. I. Ab initio studies on the first stable conformations. Int. J. Quant. Chem. 1995, 54, 313-324.
33. SYBYL, 6.03, Tripos Associates, Inc., 1699 S. Hanley Rd., Suite 303, St. Louis, MO 63144-2913.
34. JMP, 3.0, 1994; SAS Institute Inc., Cary, NC 27513.