Asymmetric syntheses, opioid receptor affinities, and antinociceptive effects of 8-amino-5,9-methanobenzocyclooctenes, a new class of structural analogues of the morphine alkaloids

Journal of Medicinal Chemistry

Volumn 39, Issue 10, 1996, Pages 1956-1966

  Schultz, Arthur G ^a   Wang, Aihua ^a   Alva, Carlos ^a   Sebastian, Alice ^a   Glick, Stanley D ^b   Deecher, Darlene C ^b   Bidlack, Jean M ^c  

^a Research Rensselaer Polytechnic Institute   (United States)

^b ALBANY MEDICAL COLLEGE   (United States)

^c UNIVERSITY OF ROCHESTER MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

3,4 DICHLORO N METHYL N [2 (1 PYRROLIDINYL)CYCLOHEXYL]BENZENEACETAMIDE; 8 AMINO 3 HYDROXY 5,9 METHANO 9 (METHOXYMETHYL) 5 METHYLBENZOCYCLOOCTENE; 8 AMINO 5,9 METHANOBENZOCYCLOOCTENE; BETA FUNALTREXAMINE; CIRAMADOL; DRUG ANALOG; ENKEPHALIN[2 DEXTRO ALANINE 4 METHYLPHENYLALANINE 5 GLYCINE]; ENKEPHALIN[2,5 DEXTRO PENICILLAMINE]; KAPPA OPIATE RECEPTOR; MORPHINE DERIVATIVE; MU OPIATE RECEPTOR; N METHYL N [7 (1 PYRROLIDINYL) 1 OXASPIRO[4.5]DEC 8 YL]BENZENEACETAMIDE; N,N DIALLYLTYROSYL 2 METHYLALANYL 2 METHYLALANYLPHENYLALANYLLEUCINE; NALOXONE; NORBINALTORPHIMINE; OPIATE AGONIST; OPIATE RECEPTOR; SIGMA OPIATE RECEPTOR; TRAMADOL; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ANTINOCICEPTION; ARTICLE; CONTROLLED STUDY; DRUG EFFECT; DRUG RECEPTOR BINDING; DRUG SYNTHESIS; ENANTIOMER; INTRACEREBROVENTRICULAR DRUG ADMINISTRATION; MALE; MOUSE; NONHUMAN; RECEPTOR AFFINITY; TAIL FLICK TEST; TISSUE HOMOGENATE; WRITHING TEST;

ALKALOIDS; ANALGESICS, OPIOID; ANIMALS; BRIDGED COMPOUNDS; MAGNETIC RESONANCE SPECTROSCOPY; MALE; MASS SPECTROMETRY; MICE; MICE, INBRED ICR; MOLECULAR STRUCTURE; RECEPTORS, OPIOID;

EID: 0029955277     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm950817g     Document Type: Article

References (47)

1. (a) Zimmerman, D. M.; Leander, J. D. Selective Opioid Receptor Agonists and Antagonists: Research Tools and Potential Therapeutic Agents. J. Med. Chem. 1990, 33, 895-902.
2. (b) McKnight, A. T.; Rees, D. C. Opioid Receptors and their Ligands. Neurotransmissions 1991, 7, 1.
3. (c) May, E. L.; Fry, E. M. Structures Related to Morphine. VIII. Further Syntheses in the Benzomorphan Series. J. Org. Chem. 1957, 22, 1366.
4. Schultz, A. G.; McCloskey, P. J.; Court, J. J. Enantioselective Conversion of Anthranilic Acid Derivatives to Chiral Cyclohexanes. Total Synthesis of (+)-Pumiliotoxin C. J. Am. Chem. Soc. 1987, 109, 6493-6502.
5. (a) McCloskey, P. J.; Schultz, A. G. Enantioselective Total Synthesis of (+)-Perhydro-219A from an Anthranilic Acid Derivative. J. Org. Chem. 1988, 53, 1380-1383.
6. (b) Daly, J. W.; Nishizawa, Y.; Padgett, W. L.; Tokuyama, T.; McCloskey, P. J.; Waykole, L.; Schultz, A. G.; Aronstam, R. S. Decahydroquinoline Alkaloids: Noncompetitive Blockers for Nicotinic Acetylcholine Receptor-Channels in Pheochromocytoma Cells and Torpedo Electroplax. Neurochem. Res. 1991, 16, 1207-1212.
7. (a) Thorp, R. H.; Walton, E.; Ofner, P. Optical Isomers of Amidone, with a Note on isoAmidone. Nature 1947, 160, 605-606.
8. (b) Eddy, N. B.; May, E. L.; Mosettig, E. Chemistry and Pharmacology of the Methadols and Acetylmethadols. J. Org. Chem. 1952, 17, 321-326.
9. (a) Lednicer, D.; Von Voigtlander, P. F.; Emmert, D. E. 4-Amino-4-Arylcyclohexanones and their Derivatives, a Novel Class of Analgesics. 1. Modification of the Aryl Ring. J. Med. Chem. 1980, 23, 424-430.
10. (b) Lednicer, D.; Von Voigtlander, P. F.; Emmert, D. E. 4-Amino-4-Arylcyclohexanones and their Derivatives, a Novel Class of Analgesics. 3. m-Hydroxyphenyl Derivatives. J. Med. Chem. 1981, 24, 341-346.
11. (c) Lednicer, D.; Von Voigtlander, P. F.; Emmert, D. E. 4-Amino-4-Arylcyclohexanones and their Derivatives, a Novel Class of Analgesics. 2. Modification of the Carbonyl Function. J. Med. Chem. 1981, 24, 404-408.
12. Yardley, J. P.; Fletcher, H.; Russell, P. B. A Potent Benzylamine Analgesic: (-)-cis-2-(a-Dimethylamino-m-hydroxybenzyl)cyclohexanol. Experienta 1978, 34, 1124-1125.
13. (a) Hennis, H. H.; Friderichs, E.; Schneider, J. Receptor Binding, Analgesic and Antitussive Potency of Tramadol and Other Selected Opioids. Arzneim-Forsch. 1988, 38, 877-880.
14. (b) For recent studies of this μ-selective, orally effective analgesic agent, see: Raffa, R. B.; Friderichs, E.; Reimann, W.; Shank, R. P.; Codd, E. E.; Vaught, J. L. Opioid and Nonopioid Components Independently Contribute to the Mechanism of Action of Tramadol, an 'Atypical' Opioid Analgesic. J. Pharmacol. Exp. Ther. 1992, 260, 275-285. Sunshine, A.; Olson, N. Z.; Zighelboim, I.; DeCastro, A.; Minn, F. L. Analgesic Oral Efficacy of Tramadol Hydrochloride in Postoperative Pain. Clin. Pharmacol. Ther. 1992, 51, 740-746.
15. (b) For recent studies of this μ-selective, orally effective analgesic agent, see: Raffa, R. B.; Friderichs, E.; Reimann, W.; Shank, R. P.; Codd, E. E.; Vaught, J. L. Opioid and Nonopioid Components Independently Contribute to the Mechanism of Action of Tramadol, an 'Atypical' Opioid Analgesic. J. Pharmacol. Exp. Ther. 1992, 260, 275-285. Sunshine, A.; Olson, N. Z.; Zighelboim, I.; DeCastro, A.; Minn, F. L. Analgesic Oral Efficacy of Tramadol Hydrochloride in Postoperative Pain. Clin. Pharmacol. Ther. 1992, 51, 740-746.
16. Freed, M. E.; Potoski, J. R.; Freed, E. H.; Conklin, G. L.; Malis, J. L. Bridged Aminotetralins as Novel Potent Analgesic Agents. J. Med. Chem. 1973, 16, 595-599.
17. Freed, M. E.; Potoski, J. R.; Conklin, G. L.; Bell, S. C. Bridged Aminotetralins. 4. Resolution of Potent Analgesics of the Bridged Aminotetralin Type. J. Med. Chem. 1976, 19, 560-562.
18. (a) Szmuszkovicz, J.; Von Voigtlander, P. F. Benzeneacetamide Amines: Structurally Novel Non-mu Opioids. J. Med. Chem. 1982, 25, 1125-1126.
19. (b) Lahti, R. A.; VonVoightlander, P. F.; Barsuhn, C. Properties of a Selective Kappa Agonist, U-50,488H. Life Sci. 1982, 31, 2257-2260.
20. (c) Katz, J. L.; Woods, J. H.; Winger, G. D.; Jacobson, A. E. Compounds of Novel Structure Having Kappa-Agonist Behavioral Effects in Rhesus Monkeys. Life Sci. 1982, 31, 2375-2378.
21. Unpublished results of C. Alva and R. K. Kullnig, RPI Laboratories.
22. Bordwell, F. G. Equilibrium Acidities in Dimethyl Sulfoxide Solution. Acc. Chem. Res. 1988, 21, 456-463.
23. Feutrill, G. I.; Mirrington, R. N. Reactions with Thioethoxide Ion in Dimethylformamide I. Selective Demethylation of Aryl Methyl Ethers. Aust. J. Chem. 1972, 25, 1719-1729.
24. A modification of a literature procedure provided material of high purity directly from the reaction mixture without additional purification; for the original procedure, see: Sheehan, J. C.; Daves, G. D. Benzoxazone Formation in the Reaction of Anthranilic Acid with Isocyanates. J. Org. Chem. 1964, 29, 3599-3601.
25. (a) Billmann, J. H.; Dorman, L. C. Reaction of 1,5-Diazacyclooctane with Aldehydes. J. Org. Chem. 1962, 27, 2419-2422.
26. (b) Kametani, T.; Kigasawa, K. Azabenzomorphane and Related Compounds. K. A Synthesis of 3-Benzyl-3,4,5,6-tetrahydro-2H-1,5-methanobenzo-[dl][1,3]diazocine. Chem. Pharm. Bull. 1966, 14, 566-571.
27. Borch, R. F.; Bernstein, M. D.; Durst, H. D. The Cyanohydridoborate Anion as a Selective Reducing Agent. J. Am. Chem. Soc. 1971, 93, 2897-2904.
28. (a) Wrobel, J. E.; Ganem, B. A General, Highly Stereoselective Synthesis of Amines. Tetrahedron Lett. 1981, 22, 3447-3450.
29. (b) Danheiser, R. L.; Morin, J. M.; Salaski, E. J. Efficient Total Synthesis of (±)-Anatoxin a. J. Am. Chem. Soc. 1985, 107, 8066-8073.
30. We found it necessary to protect the amino substituent as the tosylamide prior to C(3) methyl ether cleavage.
31. Takeda, M.; Kugita, H. Homologs of Benzomorphan Derivatives. 1. J. Med. Chem. 1970, 13, 630-634.
32. Goldenthal, E. I. A Compilation of LD50 Values in Newborn and Adult Animals. Toxicol. Appl. Pharmacol. 1971, 18, 185.
33. (a) Terenius, L. Stereospecific Interaction Between Narcotic Analgesics and a Synaptic Plasma Membrane Fraction of Rat Cerebral Cortex. Acta Pharmacol. Toxicol. 1973, 32, 317.
34. (b) Pert, C. B.; Snyder, S. H. Opiate Receptor: Demonstration in Nervous Tissue. Science 1973, 179, 1011.
35. 3H]Etorphine to Rat-Brain Homogenate. Proc. Natl. Acad. Sci. U.S.A. 1973, 70, 1947.
36. Iijima, I.; Minamikawa, J.; Jacobson, A. E.; Brossi, A.; Rice, K. Studies in the (+)-Morphinan Series, 4. A Markedly Improved Synthesis of (+)-Morphine. J. Org. Chem. 1978, 43, 1462.
37. 5]enkephalin in the Mouse. J. Pharmacol. Exp. Ther. 1987, 241, 393-400.
38. (b) Jiang, Q.; Seyed-Mozaffari, A.; Archer, S.; Bidlack, J. M. Pharmacological Study of 14β- (Thioglycolamido)-7,8-Dihydro-N-(Cyclopropylmethyl)Normorphinone (N-CPM-TAMO). J. Pharmaeol. Exp. Ther. 1993, 264, 1021-1027.
39. Portoghese, P. S.; Larson, D. L.; Sayre, L. M.; Fries, D. S.; Takemori, A. E. A Novel Opioid Receptor Site Directed Alkylating Agent with Irreversible Narcotic Antagonistic and Reversible Agonistic Activities. J. Med. Chem. 1980, 23, 233-234.
40. Cotton, R.; Giles, M. G.; Miller, L.; Shaw, J. S.; Timm, D. ICI 174,864 A Highly Selective Antagonist for the Opioid δ-Receptor. Eur. J. Pharmacol. 1984, 97, 331-332.
41. Portoghese, P. S.; Lipkowski, A. W.; Takemori, A. E. Binaltorphimine and Norbinaltorphimine, Potent and Selective k-Opioid Receptor Antagonists. Life Sci. 1987, 40, 1287-1292.
42. Mosberg, H. I.; Hurst, R.; Hruby, V. J.; Gee, K.; Yamamura, H. I.; Galligan, J. J.; Burks, T. S. Bis-penicillamine Enkephalins Possess Highly Improved Specificity Toward δ Opioid Receptor. Proc. Natl. Acad. Sci. U.S.A. 1983, 80, 5871-5874.
43. 3H]Carfentanil in Human and Rat Brain. Eur. J. Pharmacol. 1989, 167, 221-228.
44. 1 Opiate Binding Sites. Eur. J. Pharmacol. 1986, 128, 303-304.
45. 3H]U69,593 A Highly Selective Ligand for Opioid κ Receptor. Eur. J. Pharmacol. 1985, 109, 281-284.
46. Haley, T. J.; McCormick, W. G. Pharmacological Effects Produced by Intracerebral Injection of Drugs in the Conscious Mouse. Br. J. Pharmacol. Chemother. 1957, 12, 12-15.
47. Vaught, J. L.; Takemori, A. E. Differential Effects of Leucine and Methionine Enkephalin on Morphine-Induced Analgesia, Acute Tolerance and Dependence. J. Pharmacol. Exp. Ther. 1979, 206, 86-90.