Naloxone-6α-spirohydantoin: A long-acting opiate antagonist
Tóm tắt
We have synthesized a novel derivative of naloxone, naloxyl-6α-spirohydantoin. The compound was rigorously purified and its stereochemical structure characterized. In tests in vivo in mice, it was less toxic than the parent compound and it showed weak anticonvulsive activity. It exerted antagonist effects comparable to those of naloxone but its effects were longer lasting, persisting for a week.
Tài liệu tham khảo
Alexander, G. J., Medve, M., and Chatterjie, N. 1987. Opiate agonist/antagonist activity of 6-spirohydantoin derivatives of oxymorphone, oxycodone, naloxone and naltrexone. Federation Proc. 46:2036.
Chatterjie, N., and Alexander, G. J. 1984. Anticonvulsive spirohydantoin derivatives of opiate antagonists. IRCS Med. Sci. 12:340–341.
Portoghese, P. S., Larson, D. L., and Jiang, J. B. 1979. Synthesis and pharmacologic characterization of an alkylating analogue (chlornaltrexamine) of naltrexone with ultralong-lasting narcotic antagonist properties. J. Med. Chem. 22:168–173.
Caruso, T. P., Larson, D. L., Portoghese, P. S., and Takemori, A. E. 1980. Pharmacological studies with an alkylating narcotic agonist, chloroxymorphamine, and antagonist, chlornaltrexamine. J. Pharmacol. Exper. Therap. 213:539–544.
Ko, R. P., Gupte, S. M., and Nelson, W. L. 1984. Opioid agonists and antagonists, 6,6-Hydrazi- and 6-oximino derivatives of 14-hydroxy-dihydromorphinones. J. Med. Chem. 27:1727–1729.
Koman, A., Einarson, M., and Terenius, L. 1985. Agonist-antagonist properties of fluorescent opioid probes in the guinea-pig myenteric plexus-longitudinal muscle preparation. Nanuyn-Schmideberg's Arch. Pharmacol 331:355–358.
Lever, O. W., Bhatia, O. V., and Chang, K-J. 1985. Opioid receptor interactions and conformations of the 6α and 6β epimers of oxymorphamine. Solid state conformation of 6α-oxymorphamine. J. Med. chem. 28:1652–1656.
Chatterjie, N., and Alexander, G. J. 1983. Naloxone-6-spirohydantoin: a new non-toxic compound with anticonvulsive properties. Neuropharmacol. 22:1151–1153.
Alexander, G. J., Chatterjie, N., and Wisniewski, H. 1989. A spirohydantoin derivative of oxymorphone: an agonist with delayed antagonist activity. Pharmacol. Biochem. Behav. 32:939–943.
Henderson, J. D., Dayton, F. G., Israili, Z. H., and Mandell, L. 1981. A non-metabolized analog of phenytoin. J. Med. Chem. 24:843–847.
Alexander, G. J., Kopeloff, L. M., and Alexander, R. B. 1981. Metrazol thresholds in inbred and non-inbred audiosensitive mice. Neurotoxicol. 2:91–95.
Alexander, G. J., Alexander, R. B., Kopeloff, L. M., and Chatterjie, N. 1985. Comparison of anticonvulsive properties of eboracin and phenytoin in mice. Pharmacol. Biochem. Behav. 9:53–55.
Chatterjie, N., and Alexander, G. J. 1986. Anticonvulsive properties of spirhydantoin derivatives of optical isomers of camphor. Neurochem. Res. 12:1669–1676.
Chatterjie, N., Fujimoto, J. M., Inturrisi, C. E., Wang, R. I. H., Bowen, D. V., Field, F. H., and Clarke, D. D. 1974. Isolation and stereochemical identification of a metabolite of naltrexone from human urine. Drug Metab Dispos. 2:401–405.
Chatterjie, N., Inturrisi, C. E., Dayton, H. B., and Blumberg, H. 1975. Stereospecific synthesis of the 6-α hydroxy metabolites of naltrexone and naloxone. J. Med. Chem. 18:490–492.
Crouch, P. C., Bhatia, A. V., and Lever, O. W. 1983. Solution conformations of 6α and 6β epimers of oxymorphamine. Tetrah. Lett. 24:4801–4804.
Pasternak, G. W., and Hahn, E. F. 1980. Long-acting opiate agonists and antagonists, 14-hydroxydihydromorphinone hydrazones. J. Med Chem. 23:674–676.
Hahn, E. F., Carroll-Buatti, M., and Pasternak, G. W. 1982. Irreversible opiate agonist and antagonists: the 14-hydroxydihydromorphinone azines. J. Neurosci. 2:572–576.
Galetta, S., Ling, G. S. F. Wolfin, L., and Pasternak, G. W. 1982. Receptor binding and analgesic properties of oxymorphazine. Life Sci. 32:1389–1392.
Hahn, E. F., Itzhak, Y., Nishimura, S., Johnson, N., and Pasternak, G. W. 1985. Irreversible opiate agonists and antagonists. III. Phenylhydrazone derivatives of naloxone and oxymorphone. J. Pharmacol. Exper. Therap. 235:846–850.
Hahn, E. F., Nishimura, S., Goodman, P. R., and Pasternak, G. W. 1985. Irreversible opiate agonists and antagonists. II. Evidence against a bivalent mechanism of action for opiate azines and diacylhydrazones. J. Pharmacol. Exper. Therap. 235:839–845.
Luke, M. C., Hahn, E. F., Price, M., and Pasternak, G. W. 1988. Irrversible opiate agonists and antagonists. V. Hydrazone and acylhydrazone derivatives of naltrexone. Life Sci. 43:1249–1256.
Kolb, V. M., and Gober, J. R. 1983. Study of the syn and anti isomerism of the long-lasting opiate antagonist naloxazone and related compounds. Life Sci 33:419–422.
Kolb, V. M., and Hua, D. H. 1984. Syn-anti isomerism in the opiate hydrazones and azines derived from naloxone, naltrexone and morphine. J. Org. Chem. 49:3824–3828.
Jiang, J. B., Hanson, R. N., Portoghese, P. S., and Takemori, A. E. 1977. Stereochemical studies of medicinal agents. 23. Synthesis and biological elucidation of 6-amino derivatives of naloxone and naltrexone. J. Med. Chem. 20:1100–1102.