Bioisosteres of Arecoline: 1,2,3,6-Tetrahydro-5-pyridyl-Substituted and 3-Piperidyl-Substituted Derivatives of Tetrazoles and 1,2,3-Triazoles. Synthesis and Muscarinic Activity

Journal of Medicinal Chemistry

Volumn 37, Issue 24, 1994, Pages 4085-4099

  Moltzen, Ejner K ^a   Pedersen, Henrik ^a   Bøgesø, Klaus P ^a   Meier, Eddi ^a   Frederiksen, Kristen ^a   Sánchez, Connie ^a   Lembøl, Hanne Løve ^a  

^a H LUNDBECK A S   (Denmark)

Author keywords

[No Author keywords available]

Indexed keywords

1,2,3 TRIAZOLE DERIVATIVE; 2 ETHYL 4 (1,2,3,6 TETRAHYDRO 1 METHYL 5 PYRIDYL) 1,2,3 TRIAZOLE; 2 ETHYL 8 METHYL 2,8 DIAZASPIRO[4.5]DECANE 1,3 DIONE; [4 [(3 CHLOROPHENYL)CARBAMOYLOXY] 2 BUTYNYL]TRIMETHYLAMMONIUM; ALVAMELINE; ARECOLINE; CARBACHOL; LIGAND; MUSCARINIC AGENT; MUSCARINIC M1 RECEPTOR; MUSCARINIC M2 RECEPTOR; MUSCARINIC RECEPTOR; MUSCARINIC RECEPTOR BLOCKING AGENT; OXOTREMORINE; PIPERIDINE DERIVATIVE; PIRENZEPINE; QUINUCLIDINYL BENZILATE; TETRAZOLE DERIVATIVE; TRITIUM; UNCLASSIFIED DRUG;

ALZHEIMER DISEASE; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; BINDING AFFINITY; BRAIN HOMOGENATE; CONTROLLED STUDY; DEPOLARIZATION; DRUG STRUCTURE; DRUG SYNTHESIS; FEMALE; GUINEA PIG; HEART ATRIUM CONTRACTION; HYPOTHERMIA; ILEUM CONTRACTION; LIGAND BINDING; MALE; MOUSE; NONHUMAN; RAT; RECEPTOR BINDING; SALIVATION; STEREOCHEMISTRY; STRUCTURE ACTIVITY RELATION; SUPERIOR CERVICAL GANGLION; TREMOR;

ANIMAL; ARECOLINE; FEMALE; GUINEA PIGS; MALE; MICE; RATS; RATS, WISTAR; STRUCTURE-ACTIVITY RELATIONSHIP; TETRAZOLES; TRIAZOLES;

EID: 0027988563     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm00050a006     Document Type: Article

References (80)

1. Davies, P.; Maloney, A. J. F. Selective loss of central cholinergic neurons in Alzheimer's disease. Lancet 1976, No. 2, 1403.
2. Bartus, R. T.; Dean, R. L., III; Beer, B.; Lippa, A. S. The cholinergic hypothesis of geriatric memory dysfunction. Science 1982, 217, 408-417.
3. DeFeudis, F. V. Cholinergic systems and Alzheimer's disease. Drug Dev. Res. 1988, 14, 95-109.
4. Street, L. J.; Baker, R.; Book, T.; Reeve, A. J.; Saunders, J.; Willson, T.; Marwood, R. S.; Patel, S.; Freedman, S. B. Synthesis and muscarinic activity of quinuclidinyl-and (1-azanorbornyl)-pyrazine derivatives. J. Med. Chem. 1992, 35, 295-305.
5. Fibiger, H. C. Cholinergic mechanisms in learning, memory and dementia: a review of recent evidence. Trends Neurosci. 1991, 14, 220-223.
6. Holttum, J. R.; Gershon, S. The cholinergic model of dementia, Alzheimer type: progression from the unitary transmitter concept. Dementia 1992, 3, 174—185.
7. Palacios, J. M.; Spiegel, R. Muscarinic cholinergic agonists: pharmacological and clinical perspectives. Prog. Brain Res. 1986, 70, 485-498.
8. Hollander, E.; Davidson, M.; Mohs, R. C.; Horvath, T. B.; Davis, B. M.; Zemishlany, Z.; Davis, K. L. RS 86 in the treatment of Alzheimer's disease: Cognitive and biological effects. Biol. Psych. 1987, 22, 1067-1078.
9. Baker, R.; MacLeod, A. M. Muscarinic agonists for the central nervous system. In Drug design for neuroscience; Kozikowski, A. P., Ed.; Raven Press: New York, 1993; pp 61—85.
10. Gottfries, C. G.: Clinical and neurochemical aspects of diseases with cognitive impairment. Rev. Neurosci. 1992, 3, 191-206.
11. Marchbanks, R. M. Biochemistry of Alzheimer's dementia. J. Neurochem. 1982, 39, 9—15.
12. Kan, J. P.: Current and future approaches to therapy of Alzheimer's disease. Eur. J. Med. Chem. 1992, 27, 565—570.
13. Mei, L.; Roeske, W. R.; Yamamura, H. I. Molecular pharmacology of muscarinic receptor heterogeneity. Life Sci. 1989, 45, 1831-1851.
14. Watson, S.; Girdlestone, D. TIPS receptor nomenclature supplement, 4. Ed. Trends Pharmacol. Sci. 1993, March 1993 Suppl.
15. Bonner, T. I. The molecular basis of muscarinic receptor diversity. Trends Neurosci. 1989, 12, 148-151.
16. Waelbroeck, M.; Tastenoy, M.; Camus, J.; Christophe, J. Binding of selective antagonists to four muscarinic receptors (M1 to M4) in rat forebrain. Mol. Pharmacol. 1990, 38, 267-273.
17. Hulme, E. C.; Birdsall, N. J. M.; Buckley, N. J. Muscarinic receptor subtypes. Annu. Rev. Pharmacol. Toxicol. 1990, 30, 633-673.
18. Vanderheyden, P.; Gies, J.-P.; Ebinger, G.; DeKeyser, J.; Landry, Y.; Vauquelin, G. Human M1-, M2-, and M3-muscarinic cholinergic receptors: Binding characteristics of agonists and antagonists. J. Neurol. Sci. 1990, 97, 67-80.
19. Levey, A. I. Immunological localization of ml-m5 muscarinic acetylcholine receptors in peripheral tissues and brain. Life Sci. 1993, 52, 441-448.
20. Caulfield, M. P.; Higgens, G. A.; Straughan, D. W. Central administration of the muscarinic receptor subtype-selective antagonist pirenzepine selectively impairs passive avoidance learning in the mouse. J. Pharm. Pharmacol. 1983, 35, 131-132.
21. Hagan, J. J.; Jansen, J. H. M.; Broekkamp, C. L. E. Blockade of spatial learning by the Mi muscarinic antagonist pirenzepine. Pyschopharmacology 1987, 93, 470—476.
22. Messer, W. S., Jr.; Bohnett, M.; Stibbe, J. Evidence for a preferential involvement of Mi muscarinic receptors in representational memory. Neurosci. Lett. 1990, 116, 184-189.
23. Araujo, D. M.; Lapchak, P. A.; Robitaille, Y.; Gauthier, S.; Quirion, R. Differential alteration of various cholinergic markers in cortical and subcortical regions of human brain in Alzheimer's disease. J. Neurochem. 1988, 50, 1914-1923.
24. McKinney, M.; Miller, J. H.; Aagaard, P. J. Pharmacological characterization of the rat hippocampal muscarinic autoreceptor. J. Pharm. Exp. Ther. 1993, 264, 74—78.
25. Richards, M. H. Rat hippocampal muscarinic autoreceptors are similar to the M2 (cardiac) subtype: Comparison with hippocampal M1, atrial M2, and ileal M3 receptors. Br. J. Pharmacol. 1990, 99, 753-761.
26. Sánchez, C.; Meier, E.: Central and peripheral mediation of hypothermia, tremor and salivation induced by muscarinic agonists in mice. Pharmacol. Toxicol. 1993, 72, 262-267.
27. Sánchez, C.; Lembel, H. L. The involvement of muscarinic receptor subtypes in the mediation of hypothermia, tremor, and salivation in male mice. Pharmacol. Toxicol. 1994, 74, 35-39.
28. Freedman, S. B.; Dawson, G. R.; Iversen, L. L.; Baker, R.; Hargreaves, R. J. The design of novel muscarinic partial agonists that have functional selectivity in pharmacological preparations in vitro and reduced side-effect profile in vivo. Life Sci. 1993, 52, 489-495.
29. Arjungi, K. N. Areca nut. Drug Res. 1976, 26, 951-956.
30. Floersheim, P.; Pompo-Villar, E.; Shapiro, G.: Isosterism and bioisosterism case studies with muscarinic agonists. Chimia 1992, 46, 323-334.
31. 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, 33, 1128—1138.
32. Street, L. J.; Baker, R.; Book, T.; Kneen, C. O.; MacLeod, A. M.; Merchant, K. J.; Showell, G. A.; Saunders, J.; Herbert, R. H.; Freedman, S. B.; Harley, E. A.: Synthesis and biological activity of 1,2,4-oxadiazole derivatives: Highly potent and efficacious agonists for cortical muscarinic receptors. J. Med. Chem. 1990, 33, 2690-2697.
33. Freedman, S. B.; Harley, E. A.; Patel, S.; Newberry, N. R.; Gilbert, M. J.; McKnight, A. T.; Tang, J. K.; Maguire, J. J.; Mudunkotuwa, N. T.; Baker, R.; Street, L. J.; MacLeod, A. M.; Saunders, J.; Iversen, L. L. A novel series of non-quaternary oxadiazoles acting as full agonists at muscarinic receptors. Br. J. Pharmacol. 1990, 101, 575-580.
34. Freedman, S. B.; Harley, E. A.; Marwood, R. S.; Patel, S. In vivo characterization of novel efficacious muscarinic receptor agonists. Eur. J. Pharm. 1990, 187, 193—199.
35. Eglen, R. M.; Harris, G. C.; Ford, A. P. D. W.; Wong, E. H. F.; Pfister, J. R.; Whiting, R. L. The action of (±)L-660,863 [(±)3-(3-amino-1,2,4-oxadiazole-5-yl)-quinuclidine] at muscarinic receptor subtypes in vitro. Naunyn-Schmiedeberg's Arch. Pharmacol. 1992, 345, 375-381.
36. Drug News Perspect. 1993, 6, 559.
37. Abstracts and proceedings from the Third International Conference on Alzheimer's and Parkinson's Diseases, 1—6 November, 1993, Chicago, IL.
38. Sauerberg, P.; Olesen, P. H.; Nielsen, S.; Treppendahl, S.; Sheardown, M. J.; Honoré, T.; Mitch, C. H.; Ward, J. S.; Pike, A. J.; Bymaster, F. P.; Sawyer, B. D.; Shannon, H. E. Novel functional Mi selective muscarinic agonists. Synthesis and structure-activity relationships of 3-(1,2,5-thiadiazolyl)-1,2,5,6-tetrahydro-1-methylpyridines. J. Med. Chem. 1992, 35, 2274-2283.
39. Sauerberg, P.; Olesen, P. H.; Suzdak, P. D.; Sheardown, M. J.; Mitch, C. H.; Quimby, S. J.; Ward, J. S.; Bymaster, F. P.; Sawyer, B. D.; Shannon, H. E. Synthesis and structure-activity relationships of heterocyclic analogues of the functional Mi selective muscarinic agonist hexyloxy-TZTP. Bioorg. Med. Chem. Lett. 1992, 2, 809-814.
40. Ngur, D. O.; Roknich, S.; Mitch, C. H.; Quimby, S. J.; Ward, J. S.; Merritt, L.; Sauerberg, P.; Messer, W. S., Jr.; Hoss, W. Sterie and electronic requirements for muscarinic receptor-stimulated phosphoinositide turnover in the CNS in a series of arecoline bioisosteres. Biochem. Biophys. Res. Commun. 1992, 187, 1389—1394.
41. Hargreaves, R. J.; McKnight, A. T.; Scholey, K.; Newberry, N. R.; Street, L. J.; Hutson, P. H.; Semark, J. E.; Harley, E. A.; Patel, S.; Freedman, S. B. L-689, 660, a novel cholinomimetic with functional selectivity for M1 and M3 receptors. Br. J. Pharmacol. 1992, 107, 494-501.
42. Bøgesø, K. P.; Jensen, K. G.; Moltzen, E. K.; Pedersen, H. Eur. Pat. Appl. EP 296721 A2.
43. Bøgesø, K. P.; Jensen, K. G.; Moltzen, E. K.; Pedersen, H. Chem. Abstr. 1992, 110, 192831.
44. 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.
45. Jenkins, S. M.; Wadsworth, H. J.; Bromidge, S.; Orlek, B. S.; Wyman, P. A.; Riley, G. J.; Hawkins, J. Substituent variation in azabicyclic triazole-and tetrazole-based muscarinic receptor ligands. J. Med. Chem. 1992, 35, 2392—2406.
46. Birkofer, L.; Wegner, P. 1,3-Cycloadditionen mit Trimethylsilylazid; über isomere N-Acetyl-1,2,3-triazole. (1,3-Cycloadditions with Trimethylsilylazide: On Isomeric N-acetyl-1,2,3-triazole.) Chem. Ber. 1966, 99, 2512-2517.
47. Butler, R. N. Tetrazoles. In Comprehensive heterocyclic chemistry, Vol. 5; Potts, K. T., Ed.; Pergamon Press: Oxford, 1984; pp 828-834.
48. McManus, J. M.; Herbst, R. M. Tetrazole analogs of pyridinecarboxylic acid. J. Org. Chem. 1959, 24, 1462-1464.
49. Holik, M.; Ferles, M. Pyridine Series. XX. The aluminium hydride reduction of quaternary pyridinium salts. Collect. Czech. Chem. Commun. 1967, 32X, 3067-3070.
50. Cooley, J. H.; Evain, E. J. Amine dealkylations with acylchlorides. Synthesis 1989, 1-7.
51. Meyers, A. I.; Tomioka, K.; Roland, D. M.; Comins, D. Progress toward the total synthesis of maytansinoids. An efficient route to two major precursors (western-southern zone). Tetrahedron Lett. 1988, 29, 1375-1378.
52. Jacques, J.; Fouquey, C. Enantiomeric (S)-(+)-and (R)-(—)-1,1′-binaphtyl-2,2′-diyl hydrogen phosphate. Org. Synth. 1989, 67, 1-18.
53. Bøgesø, K.; Liljefors, T.; Arnt, J.; Hyttel, J.; Pedersen, H. Octoclothepin enantiomers. A reinvestigation of their biochemical and pharmacological activity in relation to a new receptorinteraction model for dopamine D-2 receptor antagonists. J. Med. Chem. 1991, 34, 2023-2030.
54. Saednya, A. Conversion of carboxamides to nitriles using trichloroacetyl chloride/triethylamine as a mild dehydrating agent. Synthesis 1985, 184-185.
55. Kozikowski, A. P.; Okita, M.; Kobayashi, M.; Floss, H. G. Probing ergot alkaloid biosynthesis: Synthesis and feeding of a proposed intermediate along the biosynthetic pathway. A new amidomalonate for tryptophan elaboration. J. Org. Chem. 1988, 53, 863-869.
56. Freedman, S. B.; Harley, E. A.; Iversen, L. L. Relative affinities of drugs acting at cholinoceptors in displacing agonist and antagonist radioligands: The NMS/Oxo-M ratio as an index of efficacy at cortical muscarinic receptors. Br. J. Pharmacol. 1988, 93, 437-445.
57. Krogsgaard-Larsen, P.; Falch, E.; Sauerberg, P.; Freedman, S. B.; Lembpl, H. L.; Meier, E. Bioisosteres of arecoline as novel CNS-active muscarinic agonists. Trends Pharmacol. Sci. 1988, Suppl., 69-74.
58. Boddeke, H. W. G. M. Different effects of muscarinic agonists in rat superior cervical ganglion and hippocampal slices. Eur. J. Pharmacol. 1991, 201, 191-197.
59. Freedman, S. B.; Beer, M. S.; Harley, E. A. Muscarinic M1, M3 receptor binding. Relationship with functional efficacy. Eur. J. Pharm. 1988, 156, 133-142.
60. Hu, J.; Wang, S.-Z.; El-Fakahany, E. E. Effects of agonist efficacy on desensitization of phosphoinositide hydrolysis mediated by m1 and m3 muscarinic receptors expressed in chínese hamster ovary cells. J. Pharm. Exp. Ther. 1991, 257, 938—945.
61. McKinney, M.; Anderson, D. J.; Vella-Rountree, L.; Connolly, T. ; Miller, J. H. Pharmacological profiles for rat cortical M1 and M2 muscarinic receptors using selective antagonists: Comparison with N1E-115 muscarinic receptors. J. Pharm. Exp. Ther. 1991, 257, 1121-1129.
62. Mei, L.; Lai, J.; Yamamura, H. I.; Roeske, W. R. Pharmacologic comparison of selected agonists for the Mi muscarinic receptor in transfected murine fibroblast cells (B82). J. Pharm. Exp. Ther. 1991, 256, 689-694.
63. Moos, W. H.; Bergmeier, S. C.; Coughenour, L. L.; Davis, R. E.; Hershenson, F. M.; Kester, J. A.; McKee, J. S.; Marriott, J. G.; Schwarz, R. D.; Tecle, H.; Thomas, A. J. Cholinergic agents: Effect of methyl substitution in a series of arecoline derivatives on binding to muscarinic acetylcholine receptors. J. Pharm. Sci. 1992, 81, 1015-1019.
64. Sauerberg, P.; Kindtler, J. W.; Nielsen, L.; Sheardown, M. J.; Honoré, T. Muscarinic cholinergic agonists and antagonists of the 3-(3-alkyl-1,2,4-oxadiazol-5-yl)-1,2,5,6-tetrahydropyridine type. Synthesis and structure-activity relationships. J. Med. Chem. 1991, 34, 687-692.
65. Showell, G. A.; Gibbons, T. L.; Kneen, C. O.; MacLeod, A. M.; Merchant, K. J.; Saunders, J.; Freedman, S. B.; Patel, S.; Baker, R. Tetrahydropyridyloxadiazoles: Semirigid muscarinic ligands. J. Med. Chem. 1991, 34, 1086-1094.
66. Tecle, H.; Lauffer, D. J.; Mirzadegan, T.; Moos, W. H.; Moreland, D. W.; Pavia, M. R.; Schwartz, R. D.; Davis, R. E. A rationale for the design and synthesis of ml selective muscarinic agonists. Bioorg. Med. Chem. Lett. 1992, 2, 821-826.
67. Toja, E.; Bonetti, C.; Butti, A.; Hunt, P.; Fortin, M.; Barzaghi, F.; Fórmente, M. L.; Maggioni, A.; Nencioni, A.; Galliani, G. 1-Substituted-1,2,5,6-tetrahydropyridine-3-carboxaldehyde-O-alkyl oximes as novel orally active and long-lasting muscarinic cholinergic agonists. Eur. J. Med. Chem. 1992, 27, 519-526.
68. Wolf-Pflugmann, M.; Lambrecht, G.; Wess, J.; Mutschler, E. Synthesis and muscarinic activity of a series of tertiary and quaternary N-substituted guvacine esters structurally related to arecoline and arecaidine propargyl ester. Drug Res. 1989, 39, 539-544.
69. Moser, U.; Lambrecht, G.; Wagner, M.; Wess, J.; Mutschler, E. Structure-activity relationships of new analogues of arecaidine propargyl ester at muscarinic M1 and M2 receptor subtypes. Br. J. Pharmacol. 1989, 96, 319-324.
70. Wess, J.; Lambrecht, G.; Moser, U.; Mutschler, E. Stimulation of ganglionic muscarinic Mi receptors by a series of tertiary arecaidine and isoarecaidine esters in the pithed rat. Eur. J. Pharm. 1987, 134, 61-67.
71. DeAmici, M.; Dallanoce, C.; DeMicheli, C.; Grana, E.; Dondi, G. ; Ladinsky, H.; Schiavi, G. B.; Zonta, F. Synthesis and pharmacological investigation of stereoisomeric muscarines. Chirality 1992, 4, 230-239.
72. Angeli, P.; Brasili, L.; Giannella, M.; Gualtieri, F.; Picchio, M. T.; Teodori, E. Chiral muscarinic agonists possessing a 1,3-oxathiolane nucleus: enantio-and tissue-selectivity on isolated preparations of guinea-pig ileum and atria and of rat urinary bladder. Naunyn-Schmiedeberg's Arch. Pharmacol. 1988, 337, 241-245.
73. Saunders, J.; Showell, G. A.; Baker, R.; Freedman, S. B.; Hill, D.; McKnight, A.; Newberry, N.; Salamone, J. D.; Hirshfield, J.; Springer, J. P. Synthesis and characterization of all four isomers of the muscarinic agonist 2′-methyl-spiro[1-azabicyclo[2.2.2]-octane-3,4′-[1,3]dioxolane]. J. Med. Chem. 1987, 30, 969-975.
74. Wei, H.; Roeske, W. R.; Lai, J.; Wanibuchi, F.; Hidaka, K.; Usuda, S. ; Yamamura, H. I. Pharmacological characterization of a novel muscarinic partial agonist, YM796, in transfected cells expressing the m1 or m2 muscarinic receptor gene. Life Sci. 1992, 50, 355-363.
75. Messer, W. S., Jr.; Ngur, D. O.; Abuh, Y. F.; Dokas, L. A.; Ting, S.-M.; Hacksell, U.; Nilsson, B. M.; Dunbar, P. G.; Hoss, W. Stereoselective binding and activity of oxotremorine analogs at muscarinic receptors in rat brain. Chirality 1992, 4, 463-468.
76. Haug, U.; Fürst, H. Darstellung und Eigenschaften der Pyridylund Chinolyl-acetylene. (Synthesis and Properties of Pjridyland Chinolylactylene.) Chem. Ber. 1960, 93, 593-598.
77. Krogsgaard-Larsen, P.; Pedersen, H.; Falch, E. Eur. Pat. Appl. EP 336555; Chem. Abstr. 1990, 112, 198366.
78. Pearson, D. E.; Hargrove, W. W.; Chow, J. K. T.; Suthers, B. R. The swamping catalyst effect. 3. The halogenation of pyridine and picolines. J. Org. Chem. 1961, 26, 789-792.
79. Arnt, J.; Lembpl, H. L.; Meier, E.; Pedersen, H. Discriminative stimulus properties of the muscarinic receptor agonists Lu 26-046 and O-Me-THPO in rats: evidence for involvement of different muscarinic receptor subtypes. Eur. J. Pharm. 1992, 218, 159-169.
80. Cheng, K.-C.; Prusoff, W. H. Relationship between the inhibition constant (K¡) and the concentration of inhibitor which causes 50 per cent inhibition (IC50) of an enzymatic reaction. Biochem. Pharmacol. 1973, 22, 3099-3090.