Trans-2-Aryl-N,N-dipropylcyclopropylamines: Synthesis and interactions with 5-HT1A receptors

Journal of Medicinal Chemistry

Volumn 39, Issue 7, 1996, Pages 1485-1493

  Vallgårda, Jerk ^a,d   Appelberg, Ulf ^a   Arvidsson, Lars Erik ^a,e   Hjorth, Stephan ^b   Svensson, Björn E ^c,f   Hacksell, Uli ^a  

^a UPPSALA UNIVERSITY   (Sweden)

^b UNIVERSITY OF GOTHENBURG   (Sweden)

^c R and D Laboratories   (Sweden)

^d PFIZER INC   (United States)

^e R D   (Sweden)

^f ASTRAZENECA R AND D   (Sweden)

Author keywords

[No Author keywords available]

Indexed keywords

2 (5 FLUORO 2 HYDROXYPHENYL) N,N DIPROPYLCYCLOPROPYLAMINE; 2 AMINOTETRALIN; 2 DIPROPYLAMINO 8 HYDROXYTETRALIN; AUTORECEPTOR; N,N DIPROPYL 2 (2 THIENYL)CYCLOPROPYLAMINE; PIPERAZINE DERIVATIVE; POSTSYNAPTIC RECEPTOR; SEROTONIN 1A AGONIST; SEROTONIN 1A RECEPTOR; UNCLASSIFIED DRUG;

ARTICLE; BINDING AFFINITY; DRUG POTENCY; RECEPTOR AFFINITY; RECEPTOR BINDING; SEROTONIN BRAIN LEVEL; SEROTONINERGIC SYSTEM; STEREOCHEMISTRY;

8-HYDROXY-2-(DI-N-PROPYLAMINO)TETRALIN; ANIMALS; BEHAVIOR, ANIMAL; BINDING, COMPETITIVE; BRAIN; CYCLOPROPANES; MAGNETIC RESONANCE SPECTROSCOPY; MALE; MOLECULAR CONFORMATION; MOLECULAR STRUCTURE; RATS; RATS, SPRAGUE-DAWLEY; RECEPTORS, SEROTONIN; RESERPINE; SEROTONIN; SEROTONIN AGONISTS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0029991883     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm9507136     Document Type: Article

References (46)

1. 1A Receptor Ligands in Animal Models of Anxiety, Impulsivity and Depression - Multiple Mechanisms of Action, Prog. Neuro-Psych. Biol. Psych. 1993, 17, 87-104.
2. (a) Glennon, R. A.; Westkaemper, R. B.; Bartyzel, P. Medicinal Chemistry of Serotonergic Agents. In Serotonin Receptor Subtypes; Peroutka, S. J., Ed.; Wiley-Liss: New York, 1991; pp 19-64.
3. (b) Arvidsson, L.-E.; Hacksell, U.; Glennon, R. A. Recent Advances in Central 5-Hydroxytryptamine Receptor Agonists and Antagonists. Prog. Drug Res. 1986, 30, 365-471.
4. 1A-Receptor Agonists and Antagonists. In Trends in Medicinal Chemistry '90; Sarel, S., Mechoulam, R., Agranat, I., Eds.; Blackwell: London, 1992; pp 113-120.
5. Arvidsson, L.-E.; Johansson, A. M.; Hacksell, U.; Nilsson, J. L. G.; Svensson, K.; Hjorth, S.; Magnusson, T.; Carlsson, A.; Lindberg, P.; Andersson, B.; Sanchez, D.; Wickstrom, H.; Sundell, S. N,N-Dialkylated Monophenolic trans-2-Phenylcyclopropylamines: Novel Central 5-Hydroxytryptamine Receptor Agonists. J. Med. Chem. 1988, 31, 92-99.
6. (a) Arvidsson, L.-E.; Hacksell, U.; Nilsson, J. L. G.; Hjorth, S. Carlsson, A.; Lindberg, P.; Sanchez, D.; Wikstrom, H. 8-Hydroxy-2-(dipropylamino)tetralin, A New Centrally Acting 5-Hydroxytryptamine Receptor Agonist. J. Med. Chem. 1981, 24, 921-923.
7. (b) Arvidsson, L.-E.; Hacksell, U.; Johansson, A. M.; Nilsson, J. L. G.; Lindberg, P.; Sanchez, D.; Wikstrom, H.; Svensson, K.; Hjorth, S.; Carlsson, A. 8-Hydroxy-2-(alkylamino)-tetralins and Related Compounds as Central 5-Hydroxytryptamine Receptor Agonists. J. Med. Chem. 1984, 27, 45-51.
8. (c) Hjorth, S.; Carlsson, A.; Lindberg, P.; Sanchez, D ; Wikström, H.; Arvidsson, L.-E.; Hacksell, U., Nilsson, J L. G. 8-Hydroxy-2-(di-n-propylamino)tetralin, 8-OH-DPAT, a potent and selective simplified ergot congener with central 5-HT-receptor stimulating activity. J. Neural Transm 1982, 55, 169-188.
9. 1A Receptors That Are Negatively Coupled to Adenylate Cyclase. Mol. Pharmacol 1991, 39, 780-787.
10. Jeffery, T. Highly Stereospecific Palladium-Catalysed Vinylation of Vinylic Halides Under Solid-liquide Phase Transfer Conditions. Tetrahedron Lett. 1985, 26, 2667-2670.
11. (a) Vallgårda, J.; Appelberg, U.; Csöregh, I.; Hacksell, U. Stereoselectivity and Generality of the Palladium-Catalysed Cyclopropanation of α,β-Unsaturated Carboxylic Acids Derivatized with Oppolzer's Sultam. J. Chem. Soc., Perkin Trans. 1 1994, 461-470.
12. (b) Vallgårda, J.; Hacksell, U. Stereoselective Palladium-Catalyzed Cyclopropanation of α,β-Unsaturated Carboxylic acids Derivatized with Oppolzer's Sultam. Tetrahedron Lett. 1991, 32, 5625-5628; 7136.
13. Paulissen, R.; Hubert, A. J.; Teyssie, Ph. Transition Metal Catalysed Cyclopropanation of Olefins. Tetrahedron Lett. 1972, 15, 1465-1466.
14. Shioiri, T.; Ninomiya, K.; Yamada, S. Diphenylphosphoryl Azide A New Convenient Reagent for a Modified Curtius Reaction and for the Peptide Synthesis. J. Am. Chem. Soc. 1972, 94, 6203-6205.
15. (a) Carpino, L. A.; Tsao, A. C. Convenient Source of 'Naked' Fluoride: Tetra-n-butylammonium Chloride and Potassium Fluoride Dihydrate. J. Chem. Soc., Chem. Commun. 1979, 514-515.
16. (b) Capson, T. L.; Thompson, M. D.; Dixit, V. M.; Gaughan, R. G.; Poulte, C. D. Synthesis of Ammonium Analogues of Carbocationic Intermediates in the Conversion of Presqualene Diphosphate to Squalene. J. Org. Chem. 1988, 53, 5903-5908.
17. Jung, M. E.; Lyster, M. A. Conversion of Alkyl Carbamates into Amines via Treatment with Trimethylsilyl Iodide. J. Chem. Soc., Chem. Commun. 1978, 315-316.
18. Andén, N.-E.; Carlsson, A.; Häggendal, J. Adrenergic mechanisms. Annu. Rev. Pharmacol. 1969, 9, 119-134.
19. Aghajanian, G. K. Feedback regulation of central monoaminergic neurons: evidence from single cell recording studies. In Essays in neurochemistry and neuropharmacology; Youdim, M. B. H., Lovenberg, W., Sharman, D. F., Lagnado, J. R., Eds.; John Wiley & Sons: New York, 1978; pp 2-32.
20. 1A agonist 8-OH-DPAT preferentially activates cell body 5-HT autoreceptors in rat brain in vivo. Naunyn-Schmiedeberg's Arch. Pharmacol. 1988, 338, 463-471.
21. Neckers, L. M.; Neuf, N. H.; Wyatt, R. J. Increased Serotonin turnover in corpus striatum following an injection of kainic acid: evidence for neuronal feedback regulation of synthesis. Naunyn-Schmiedeberg's Arch. Pharmacol. 1979, 306, 173-177.
22. 1A receptor interactions. Although this possibility cannot be unambiguously excluded for the novel compounds, a number of factors support the notion that MAO B inhibition is irrelevant: (i) MAO inhibitors like tranylcypromine significantly reduce 5-HIAA levels to about 80-90% of control levels. In contrast, the 5-HIAA decrease induced by the compounds studied herein does not exceed 20% of controls. (ii) The DOPAC levels are only affected by one of the novel compounds and the reduction amounts to only about 40% of the control values. (iii) The in vivo effects of the lead compounds for the present study, (1R,2S)-1 and (1R,2S)-2, have been demonstrated to be unrelated to indirect effects, such as MAO inhibition, because their in vivo effects persisted after the combined treatment with the monoamine depletor reserpine and the 5-HT synthesis inhibitor H 22/ 54 (ref 3). It is very unlikely that the structural changes introduced in the novel compounds would enhance their ability to inhibit MAO B. (iv) Although primary amines may be good MAO-inhibitors, this activity is normally reduced or lost in the tertiary amino analogues.
23. 1 receptor and of catecholaminergic systems in the behavioural response to 8-hydroxy-2-(di-n-propylamino)-tetralin in the rat. Eur. J. Pharmacol. 1985, 106, 271-282.
24. 1A Receptors. Bioorg. Med. Chem. Lett. 1991, 1, 257-262.
25. 1A Receptors. J. Med. Chem. 1993, 36, 4221-4229.
26. Arvidsson, L.-E.; Karlén, A.; Norinder, U.; Kenne, L.; Sundell, S.; Hacksell, U. Structural Factors of Importance for 5-Hydroxytryptaminergic Activity. Conformational Preferences and Electrostatic Potentials of 8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and Some Related Agents. J. Med. Chem. 1988, 31, 212-221.
27. 1A-Receptor Agonists Based on Stereoselective Methyl-Substituted and Conformationally Restricted Analogues 8-Hydroxy-2-(dipropylamino)tetralin. J. Med. Chem. 1991, 34, 497-510.
28. 1A Receptors Negatively Coupled to Adenylyl Cyclase Activity in Rat Hippocampal Membranes. Mol. Pharmacol. 1992, 41, 1066-1072.
29. 1A-Receptor Antagonist. J. Med. Chem. 1990, 33, 1541-1544.
30. 1A Receptor Antagonist (S)-5-Fluoro-8-hydroxy-2-(dipropylamino)-tetralin: Inhibition of (R)-8-Hydroxy-2-(dipropylamino)tetralin-Induced Effects. J. Pharmacol. Exp. Ther. 1991, 258, 58-65.
31. Gaertner, R. Bromination, Iodination and Phenylation of Thianaphthenes. J. Am. Chem. Soc. 1952, 74, 4950-4951.
32. Black, T. H. The Preparation and Reactions of Diazomethane. Aldrichimica Acta 1983, 16, 3-10.
33. Carlsson, A.; Lindquist, M. Effect of ethanol on the hydroxylation of tyrosine and tryptophan in rat brain in vivo. J. Pharm. Pharmacol. 1973, 25, 437-440.
34. Shum, A.; Sole, M. J.; van Loon, G. R. Simultaneous measurement of 5-hydroxytryptophan and L-dihydroxyphenylalanine by high performance liquid chromatography with electrochemical detection. Measurement of serotonin and catecholamine turnover in discrete brain regions. J. Chromatogr. 1982, 228, 123-130.
35. 1A receptors: Behavioural and in vivo brain microdialysis studies. Life Sci. 1990, 46, 955-963.
36. Munson, P. J.; Rodbard, D. LIGAND: A Versatile Computerized Approach for Characterization of Lagand-Binding Systems. Anal. Biochem. 1980, 107, 220-239.
37. Jackson, D. M.; Mohell, N.; Georgiev, J.; Bengtsson, A.; Larsson, L.-G.; Magnusson, O.; Ross, S. B. Time course of bromocriptine induced excitation in the rat: behavioural and biochemical studies. Naunyn-Schmiedeberg's Arch. Pharmacol. 1995, 351, 146-155.
38. Buckle, D. R. Arachidonic Acid Analogues, Processes for Their Preparation and Their Use in Medicine. European Patent 0109 225 A1, 1983.
39. Beck, M.; Jaunich, S.; Frahm, A. W. Synthese Kernfluorierter Stereomerer 3-Oxo-5-phenyl-1-cyclopentancarbonsäuren. (Stereochemistry of 3-oxo-5-phenyl-cyclopentanecarboxylic acids, IX: Synthesis of stereoisomeric 5-(fluorophenyl)-3-oxocyclopentanecarboxylic acids.) Arch. Pharm. 1986, 319, 29-37.
40. Collins, R. J.; Brown, E. V. Heterocyclic Analogs of the Estrogenic Steroid Hormones. I. Synthesis of a Thiophene Analog of 3-Desoxyisoequilenin. J. Am. Chem. Soc. 1957, 79, 1103-1107.
41. 13C N.M.R. Spectroscopy for the Identification of E- and Z-α,β-Unsaturated Esters, Ketones and Nitriles J. Chem. Res. Miniprint 1984, 2801-2809.
42. Satonaka, A. 1H-NMR Data for Methyl trans-β-(2-,4-, and 5-Substituted-3-thienyl)acrylates. Magn. Reson. Chem. 1986, 24, 265-267.
43. Burger, A.; Yost, W. Arylcyclopropylamines. I. 2-Phenylcyclopropylamine. J. Am. Chem. Soc. 1948, 70, 2198-2201.
44. Kaiser, C.; Lester, B. M.; Zirkle, C. L.; Burger, A.; Davis, C. S.; Delia, T. J.; Zirngibl, L. 2-Substituted Cyclopropylamines. I. Derivatives and Analogs of 2-Phenylcyclopropylamine. J. Med. Pharm. Chem. 1962, 5, 1243-1265.
45. McFarland, J. W. On the Isomers of 2-(2-Thienyl)- and 2-Phenylcyclopropanecarboxylic Acid. J. Org. Chem. 1965, 30, 3298-3301.
46. Kang, G. I.; Hong, S. K. Quantitative Structure-Activity Relationship in MAO-Inhibitory 2-Phenylcyclopropylamines: Insight into the Topography of MAO-A and MAO-B. Arch. Pharm. Res. 1990, 13, 82-96.