(R)-11-Hydroxy- and (R)-11-Hydroxy-10-methylaporphine: Synthesis, Pharmacology, and Modeling of D2A and 5-HT1A Receptor Interactions

Journal of Medicinal Chemistry

Volumn 38, Issue 4, 1995, Pages 647-658

  Hedberg, Martin H ^a   Johansson, Anette M ^a   Nordvall, Gunnar ^a   Yliniemelä, Ari ^a,b   Li, Hong Bing ^c   Martin, Arnold R ^c   Hjorth, Stephan ^d   Unelius, Lena ^e   Sundell, Staffan ^d   Hacksell, Uli ^a  

^a UPPSALA UNIVERSITY   (Sweden)

^b VTT TECHNICAL RESEARCH CENTRE OF FINLAND   (Finland)

^c UNIVERSITY OF ARIZONA   (United States)

^d UNIVERSITY OF GOTHENBURG   (Sweden)

^e CNS Preclinical R&D ^*  (Sweden)

Author keywords

[No Author keywords available]

Indexed keywords

11 HYDROXY 10 METHYLAPORPHINE; 11 HYDROXYAPORPHINE; 2 DIPROPYLAMINO 8 HYDROXYTETRALIN; 3,4 DIHYDROXYPHENYLACETIC ACID; 5 HYDROXYINDOLEACETIC ACID; 8 CHLORO 2,3,4,5 TETRAHYDRO 3 METHYL 5 PHENYL 1H 3 BENZAZEPIN 7 OL HYDROGEN MALEATE; APORPHINE DERIVATIVE; DIHYDROXYPHENYLACETIC ACID; DOPAMINE 2 RECEPTOR; FORSKOLIN; PINDOLOL; RACLOPRIDE; SEROTONIN; SEROTONIN 1A RECEPTOR; SEROTONIN AGONIST; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DRUG BINDING SITE; DRUG CONFORMATION; DRUG EFFICACY; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG SELECTIVITY; DRUG STRUCTURE; DRUG SYNTHESIS; MALE; NONHUMAN; RAT; SUBCUTANEOUS DRUG ADMINISTRATION;

ADENYLATE CYCLASE; ANIMAL; APORPHINES; COMPUTER GRAPHICS; CRYSTALLOGRAPHY, X-RAY; ENZYME ACTIVATION; FORSKOLIN; HUMAN; MALE; MICRODIALYSIS; RATS; RATS, SPRAGUE-DAWLEY; RECEPTORS, DOPAMINE D2; SEROTONIN AGONISTS; SUPPORT, NON-U.S. GOV'T;

EID: 0029017726     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm00004a011     Document Type: Article

References (66)

1. Matthiessen, A.; Wright, C. R. A. Proc. R. Soc. London, Ser. B 1869, 17, 455.
2. Goldman, M. E.; Kebabian, J. W. Aporphine enantiomers. Interactions with D-1 and D-2 dopamine receptors. Mol. Pharmacol. 1984, 25, 18-23.
3. Baldessarini, R. J.; Kula, N. S.; Zong, R.; Neumeyer, J. L. Receptor affinities of aporphine enantiomers in rat brain tissue. Eur. J. Pharmacol. 1994, 254, 199-203.
4. Schaus, J. M.; Titus, R. D.; Foreman, M. M.; Mason, N. R.; Truex, L. L. Aporphines as antagonists of dopamine receptors. J. Med. Chem. 1990, 33, 600-607.
5. Neumeyer, J. L.; Granchelli, F. E.; Fuxe, K.; Ungerstedt, U.; Corrodi, H. Aporphines. 11. Synthesis and dopaminergic activity of monohydroxyaporphines. Total synthesis of (±)-11-hydroxyaporphine, (±)-11-hydroxynoraporphine, and (±)-11-hydroxy-N-n-propylnoraporphine. J. Med. Chem. 1974, 17, 1090-1095.
6. Cannon, J. G.; Mohan, P.; Bojarski, J.; Long, J. P.; Bhatnagar, R. K.; Leonard, P. A.; Flynn, J. R.; Chatteijee, T. K. (f1)-10-Methyl-11-hydroxyaporphine: A highly selective serotonergic agonist. J. Med. Chem. 1988, 31, 313-318.
7. Ram, V. J.; Neumeyer, J. L. Aporphines. 42. Synthesis of (R)-(-)-11-hydroxyaporphines from morphine. J. Org. Chem. 1982, 47, 4372-4374.
8. Hedberg, M. H.; Johansson, A. M.; Hacksell, U. Facile syntheses of aporphine derivatives. J. Chem. Soc., Chem. Commun. 1992, 845-846.
9. Echavarren, A. M.; Stille, J. K. Palladium-catalyzed coupling of aryl triflates with organostannanes. J. Am. Chem. Soc. 1987, 109, 5478-5486.
10. Murahashi, S.-I.; Hirano, T.; Yano, T. Palladium catalyzed amine exchange reaction of tertiary amines. Insertion of palladium (O) into carbon-hydrogen bonds. J. Am. Chem. Soc. 1978, 100, 348-350.
11. Murahashi, S.-I.; Watanabe, T. Palladium catalyzed hydrolysis of tertiary amines with water. J. Am. Chem. Soc. 1979, 101, 7429-7430.
12. McCrindle, R.; Ferguson, G.; Arsenault, G. J.; McAlees, A. J.; Stephenson, D. K. Formation and characterisation of enamine complexes of palladium (II) chloride, crystal structure analysis of di-chlorobis[2-(AW-diisopropylimino) ethyl-C]-dipalladium (II). J. Chem. Res., Symp. 1984, 360-361.
13. Cabri, W.; Candiani, I.; DeBemardinis, S.; Francalanci, F.; Penco, S. Heck reaction on anthraquinone derivatives: ligand, solvent, and salt effects. J. Org. Chem. 1991, 56, 5796-5800.
14. Saá, J. M.; Dopico, M.; Martorell, G.; Garcia-Raso, A. Deoxygenation of highly hindered phenols. J. Org. Chem. 1990, 55, 991-995.
15. Stokker, G. E. Palladium catalyzed stereospecific Michael arylation of 6-alkyl-5, 6-dihydro-2H-pyran-2-ones. Tetrahedron Lett. 1987, 28, 3179-3182.
16. Martorell, G.; Garcia-Raso, A.; Saá, J. M. Palladium catalyzed cross-coupling of phenol triflates with organostannanes. A versatile approach for the synthesis of substituted resorcinol dimethyl ethers. Tetrahedron Lett. 1990, 31, 2357-2360.
17. Saá, J. M.; Martorell, G.; Garcia-Raso, A. Palladium-catalyzed cross-coupling reactions of highly hindered, electron-rich phenol triflates and organostannanes. J. Org. Chem. 1992, 57, 678-685.
18. Giesecke, J. The crystal and molecular structure of apomorphine hydrochloride hydrate. Acta Crystallogr. 1973, 29, 1785-1791.
19. Johansson, A. M.; Karlen, A.; Grol, C. J.; Sundeil, S.; Kenne, L.; Hacksell, U. Dopaminergic 2-aminotetralins: affinities for dopamine D2-receptors, molecular structures, and conformational preferences. Mol. Pharmacol. 1986, 30, 258-269.
20. Liljefors, T.; Wikström, H. A. Molecular mechanics approach to the understanding of presynaptic selectivity for centrally acting dopamine receptor agonists of the phenylpiperidine series. J. Med. Chem. 1986, 29, 1896-1904.
21. Froimowitz, M.; Neumeyer, J. L.; Baldessarini, R. J. A stereochemical explanation of the dopamine agonist and antagonist activity of stereoisomeric pairs. J. Med. Chem. 1986, 29, 1570-1573.
22. Cahn, R. S.; Ingold, C.; Prelog, V. Spezifikation der molekularen chiralität. (Specification of molecular chirality). Angew. Chem. 1966, 78, 413-447.
23. Jansen, J. M.; Karlén, A.; Grol, C. J.; Hacksell, U. Conformational properties of melatonin and two conformationally restricted agonists: A molecular mechanics and NMR spectroscopic study. Drug Des. Discovery 1993, 10, 115-133.
24. Wikström, H.; Lii, J.-H.; Allinger, N. The dopaminergic moiety of the ergots: A controversial topic studied with molecular mechanics. J. Med. Chem. 1987, 30, 1928-1934.
25. Nordvall, G.; Hacksell, U. Binding-site modeling of the muscarinic ml receptor: A combination of homology-based and indirect approaches. J. Med. Chem. 1993, 36, 967-976.
26. Malmberg, Å.; Nordvall, G.; Johansson, A. M.; Mohell, N.; Hacksell, U. Molecular basis for the binding of 2-aminotetralins to human dopamine D2A and D3 receptors. Mol. Pharmacol. 1994, 46, 299-312.
27. Kobilka, B. K.; Frielle, T.; Collins, S.; Yang-Feng, T.; Kobilka, T. S.; Francke, U.; Lefkowitz, R. J.; Caron, M. G. An intronless gene encoding a potential member of the family of receptors coupled to guanine nucleotide regulatory proteins. Nature 1987, 329, 75-79.
28. Fargin, A.; Raymond, J. R.; Lohse, M. J.; Kobilka, B. K.; Caron, M. G.; Lefkowitz, R. J. The genomic clone G-21 which resembles a β-adrenergic receptor sequence encodes the 5-HTia receptor. Nature 1988, 335, 358-360.
29. Trumpp-Kallmeyer, S.; Hoflack, J.; Bruinvels, A.; Hibert, M. Modeling of G-protein-coupled receptors: Application to dopamine, adrenaline, serotonin, acetylcholine, and mammalian opsin receptors. J. Med. Chem. 1992, 35, 3448-3462.
30. Sylte, I.; Edvardsen, O.; Dahl, S. G. Molecular dynamics of the 5-HT (1a) receptor and ligands. Protein Eng. 1993, 6, 691-700.
31. Kuipers, W.; Van Wijngaarden, I.; Ijzerman, A. P. A model of the serotonin 5-HTIA receptor: Agonist and antagonist binding sites. Drug Des. Discovery 1994, 11, 231-249.
32. Dijkstra, G. D. H.; Tulp, M. T. M.; Hermkens, P. H. H.; van Maarseveen, J. H.; Scheeren, H. W.; Kruse, C. G. Synthesis and receptor-affinity profile of N-hydroxytryptamine derivatives for serotonin and tryptamine receptors. A molecular-modelling study. Reel. Trav. Chim. Pays-Bas 1993, 112, 131-136.
33. Mellin, C.; Vallgårda, J.; Nelson, D. L.; Björk, L.; Yu, H.; Andén, N.-E.; Csöregh, I.; Arvidsson, L.-E.; Hacksell, U. A 3-D model for 5-HTiA-receptor agonists based on stereoselective methyl-substituted and conformationally restricted analogues of 8-hydroxy-2-(dipropylamino) tetralin. J. Med. Chem. 1991, 34, 497-510.
34. Nordvall, G. Unpublished results.
35. Chanda, P. K.; Minchin, M. C. W.; Davis, A. R.; Greenberg, L.; Reilly, Y.; McGregor, W. H.; Bhat, R.; Lübeck, M. D.; Mizutani, S.; Hung, P. P. Identification of residues important for ligand binding to the human 5-hydroxytryptamineiA serotonin receptor. Mol. Pharmacol. 1993, 43, 516-520.
36. Ho, B. Y.; Karschin, A.; Branchek, T.; Davidson, N.; Lester, H. A. The role of conserved aspartate and serine residues in ligand binding and in function of the 5-HTia receptor-A site-directed mutation study. FEBS Lett. 1992, 312, 259-262.
37. Strader, C. D.; Sigal, I. S.; Register, R. B.; Candelore, M. R.; Rands, E.; Dixon, R. A. F. Identification of residues required for ligand binding to the beta-adrenergic receptor. Proc. Natl. Acad. Sci. U. SA. 1987, 84, 4384-4388.
38. Wang, C. D.; Buck, M. A.; Fraser, C. M. Site-directed mutagenesis of α2A-adrenergic receptors-identification of amino acids involved in ligand binding and receptor activation by agonists. Mol. Pharmacol. 1991, 40, 168-179.
39. Neve, K. A.; Cox, B. A.; Henningsen, R. A.; Spanoyannis, A.; Neve, R. L. Pivotal role for aspartate-80 in the regulation of dopamine D2 receptor affinity for drugs and inhibition of adenylyl cyclase. Mol. Pharmacol. 1991, 39, 733-739.
40. Horstman, D. A.; Brandon, S.; Wilson, A. L.; Guyer, C. A.; Cragoe, E. J., Jr.; Limbird, L. E. An aspartate conserved among G-protein receptors confers allosteric regulation of α2-adrenergic receptors by sodium. J. Biol. Chem. 1990, 265, 21590-21595.
41. Cox, B. A.; Henningsen, R. A.; Spanoyannis, A.; Neve, R. L.; Neve, K. A. Contributions of conserved serine residues in the interactions of ligands with dopamine D2 receptors. J. Neurochem. 1992, 59, 627-635.
42. Seeman, P.; Ulpian, C.; Grigoriadis, D.; Pri-Bar, I.; Buchman, O. Conversion of dopamine Di receptors from high to low affinity for dopamine. Biochem. Pharmacol. 1985, 34, 151-154.
43. Grigoriadis, D.; Seeman, P. Complete conversion of brain D2 dopamine receptors from the high- to the low-affinity state for dopamine agonists, using sodium ions and guanine nucleotide. J. Neurochem. 1985, 44, 1925-1935.
44. DeVivo, M.; Maayani, S. Characterization of the 5-hydroxytryptamineiA receptor-mediated inhibition of forskolin-stimulated adenylyl cyclase activity in guinea pig and rat hippocampal membranes. J. Pharmacol. Exp. Ther. 1986, 238, 248-253.
45. Sharp, T.; Bramwell, S. R.; Clark, D.; Grahame-Smith, D. G. In vivo measurement of extracellular 5-hydroxytryptamine in hippocampus of the anesthetized rat using microdialysis: Changes in relation to 5-hydroxytryptaminergic neuronal activity. J. Neurochem. 1989, 53, 234-240.
46. Hjorth, S.; Sharp, T.; Liu, Y. Cis-(-)-8-OH-1-CH3-DPAT, (+)-ALK-3, a novel stereoselective pharmacological probe for characterizing 5-HT release-controlling 5-HTIA autoreceptors. An in vivo brain microdialysis study. Naunyn-Schmiedeberg’s Arch. Pharmacol. 1990, 341, 149-157.
47. Vahabzadeh, A.; Fillenz, M. Studies on the origin of rat hippocampal dihydroxyphenylacetic acid using microdialysis. Neurosci. Lett. 1992, 136, 51-55.
48. Björk, L.; Cornfield, L. J.; Nelson, D. L.; Hillver, S.-E.; Andén, N.-E.; Lewander, T.; Hacksell, U. Pharmacology of the novel 5-hydroxytryptamineiA receptor antagonist (S)-5-fluoro-8-hydroxy-2-(dipropylamino) tetralin: Inhibition of CR)-8-hydroxy-2-(dipropylamino) tetralin-induced effects. J. Pharmacol. Exp. Ther. 1991, 258, 58-65.
49. Neville, G. A.; Ekiel, I. and Smith, I. C. P. High-resolution proton magnetic resonance spectra of morphine and its three O-acetyl derivatives. Magn. Reson. Chem. 1987, 25, 31-35.
50. Carroll, F. I.; Moreland, C. G.; Brine, G. A.; Kepler, J. A. Carbon-13 nuclear magnetic resonance spectra of morphine alkaloids. J. Org. Chem. 1976, 41, 996-1001.
51. Cannon, J. G.; Moe, S. T.; Long, J. P. Enantiomers of 11-hydroxy-10-methylaporphine having opposing pharmacological effects at 5-HTIA receptors. Chirality 1991, 3, 19-23.
52. Cacchi, S.; Ciattini, P. G.; Morera, E.; Ortar, G. Palladium-catalyzed triethylammonium formate reduction of aryl triflates. A selective method for the deoxygenation of phenols. Tetrahedron Lett. 1986, 27, 5541-5544.
53. Reden, J.; Reich, M. F.; Rice, K. C.; Jacobson, A. E.; Brossi, A. Deoxymorphines: Role of the phenolic hydroxyl in antinociception and opiate receptor interactions. J. Med. Chem. 1979, 22, 256-259.
54. Gilmore, C. J. MITHRIL-an integrated direct-methods computer program. J. Appl. Crystallogr. 1984, 17, 42-46.
55. Gabe, E. J.; LePage, Y.; Charland, J.-P.; Lee, F. L.; White, P. S. NRCVAX-an interactive program system for structure analysis. J. Appi. Crystallogr. 1989, 22, 384-387.
56. Sprague, J. T.; Tai, J. C.; Yuh, Y.; Allinger, N. L. The MMP2 calculational method. J. Comput. Chem. 1987, 8, 581-603.
57. Allinger, N. L.; Yuh, Y. Quantum Chemistry Program Exchange 1980, 12, 395.
58. Burkert, U.; Allinger, N. L. Molecular Mechanics; American Chemical Society: Washington, DC, 1982.
59. Henderson, R.; Baldwin, J. M.; Ceska, T. A.; Zemlin, F.; Beckmann, E.; Downing, K. H. Model for the structure of bacteriorhodopsin based on high-resolution electron cryomicros-copy. J. Mol. Biol. 1990, 213, 899-929.
60. Munson, P. J.; Rodbard, D. LIGAND: A versatile computerized approach for characterization of ligand-binding systems. Anal. Biochem. 1980, 107, 220-239.
61. Malmberg, A.; Jackson, D. M.; Eriksson, A.; Mohell, N. Unique binding characteristics of antipsychotic agents interacting with human dopamine D2A, D2B, and D3 receptors. Mol. Pharmacol. 1993, 43, 749-754.
62. Hall, H.; Sällemark, M.; Jeming, E. Effects of remoxipride and some related new substituted salicylamides on rat brain receptors. Acta Pharmacol. Toxicol. 1986, 58, 61-70.
63. Salomon, Y. Adenylyl cyclase assay. Adv. Cyclic Nucleotide Res. 1979, 10, 35-55.
64. Lowry, O. H.; Rosebrough, N. J.; Farr, A. L.; Randall, R. J. Protein measurement with the folin phenol reagent. J. Biol. Chem. 1951, 193, 265-275.
65. Paxinos, S.; Watson, C. The rat brain in stereotaxic coordinates; Academic Press: Sydney, 1982.
66. Tao, R.; Hjorth, S. α2-Adrenoceptor modulation of 5-hydroxytryptamine release in rat ventral hippocampus in vivo. Naunyn-Schmiedeberg’s Arch. Pharmacol. 1992, 345, 137-143.