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Probes for narcotic receptor mediated phenomena. 5. Narcotic antagonist irreversible ligands based on endoethenotetrahydrooripavine

Jacobson, A.E.; Bajwa, B.S.; Streaty, R.A.; Klee, W.A.; Rice, K.C.

Life Sciences 33 Suppl. 1: 159-162

1983

ISSN/ISBN: 0024-3205
PMID: 6319854
DOI: 10.1016/0024-3205(83)90468-x
Accession: 044040258
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Nine new compounds have been synthesized as potential affinity ligands for specific opioid receptors. The biochemical properties of three of these compounds were examined in detail and one of them, N-cyclopropylmethyl-7 alpha-methylfumaroylamido-6, 14-endoethenotetrahydronororipavine (NIH 10236), was found to be a potent irreversible ligand for the delta opioid receptor. It had the properties of a narcotic antagonist, as determined by its effect on adenylate cyclase activity of NG108-15 neuroblastoma-glioma cell homogenates. It is, thus, the first delta specific alkylating ligand known which is a narcotic antagonist. A second compound, the N-cyclopropylmethyl-7 alpha-isothiocyanato-6, 14-endoethenotetrahydronororipavine (NIH 10235) was found to be a mu specific alkylating ligand in brain and a reversible antagonist in the NG108-15 cells.

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Related References

Lessor, R.A.; Bajwa, B.S.; Rice, K.C.; Jacobson, A.E.; Streaty, R.A.; Klee, W.A.; Smith, C.B.; Aceto, M.D.; May, E.L.; Harris, L.S. 1986: Probes for narcotic receptor mediated phenomena. 13. Potential irreversible narcotic antagonist-based ligands derived from 6,14-endo-ethenotetrahydronororipavine with 7-(methoxyfumaroyl)amino, (bromoacetyl)amino, or isothiocyanate electrophiles: chemistry, biochemistry, and pharmacology Journal of Medicinal Chemistry 29(11): 2136-2141
Burke, T.R.; Bajwa, B.S.; Jacobson, A.E.; Rice, K.C.; Streaty, R.A.; Klee, W.A. 1984: Probes for narcotic receptor mediated phenomena. 7. Synthesis and pharmacological properties of irreversible ligands specific for mu or delta opiate receptors Journal of Medicinal Chemistry 27(12): 1570-1574
Burke, T.R.J. ; Rice, K.C.; Jacobson, A.E.; Simonds, W.F.; Klee, W.A. 1984: Probes for narcotic receptor mediated phenomena 8. tritiation of irreversible mu or delta specific opioid receptor affinity ligands to high specific activity Journal of Labelled Compounds and Radiopharmaceuticals 21(8): 693-702
Lessor, R.A.; Rice, K.C.; Streaty, R.A.; Klee, W.A.; Jacobson, A.E. 1984: Probes for narcotic receptor mediated phenomena. 10. Irreversible ligands to opioid receptors based on biologically potent endoethenooripavines. Reversible binding of fit to mu and delta opioid receptors Neuropeptides 5(1-3): 229-232
Zhang, X.; Rice, K.C.; Calderon, S.N.; Kayakiri, H.; Smith, L.; Coop, A.; Jacobson, A.E.; Rothman, R.B.; Davis, P.; Dersch, C.M.; Porreca, F. 1999: Probes for narcotic receptor mediated phenomena. 26. Synthesis and biological evaluation of diarylmethylpiperazines and diarylmethylpiperidines as novel, nonpeptidic delta opioid receptor ligands Journal of Medicinal Chemistry 42(26): 5455-5463
Iyer, M.R.; Lee, Y.S.; Deschamps, J.R.; Dersch, C.M.; Rothman, R.B.; Jacobson, A.E.; Rice, K.C. 2012: Probes for narcotic receptor mediated phenomena. 44. Synthesis of an N-substituted 4-hydroxy-5-(3-hydroxyphenyl)morphan with high affinity and selective μ-antagonist activity European Journal of Medicinal Chemistry 50: 44-54
Bertha, C.M.; Flippen-Anderson, J.L.; Rothman, R.B.; Porreca, F.; Davis, P.; Xu, H.; Becketts, K.; Cha, X.Y.; Rice, K.C. 1995: Probes for narcotic receptor-mediated phenomena. 20. Alteration of opioid receptor subtype selectivity of the 5-(3-hydroxyphenyl)morphans by application of the message-address concept: Preparation of delta-opioid receptor ligands Journal of Medicinal Chemistry 38(9): 1523-1537
De Costa, B.R.; Rothman, R.B.; Bykov, V.; Band, L.; Pert, A.; Jacobson, A.E.; Rice, K.C. 1990: Probes for narcotic receptor mediated phenomena. 17. Synthesis and evaluation of a series of trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]benzeneacet amide (U50,488) related isothiocyanate derivatives as opioid receptor affinity ligands Journal of Medicinal Chemistry 33(4): 1171-1176
Linders, J.; Mirsadeghi, S.; Flippen-Anderson, J.; George, C.; Jacobson, A.; Rice, K. 2003: Probes for Narcotic Receptor Mediated Phenomena Helvetica Chimica Acta 86(2): 484-493
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Hashimoto, A.; Linders, J.T.M.; Kodato, S.; Jacobson, A.E.; Rice, K.C. 2002: Oxide-bridged 5- -2-methylmorphans as probes for narcotic-receptor-mediated phenomena Drug and Alcohol Dependence 66(Suppl 1): S76
Linders, J.T.; Burke, T.R.; Jacobson, A.E.; Rice, K.C. 1990: Oxide-bridged 5-phenylmorphans as probes for narcotic receptor mediated phenomena Nida Research Monograph 105: 388-389
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Iyer, M.R.; Rothman, R.B.; Dersch, C.M.; Jacobson, A.E.; Rice, K.C. 2013: Probes for narcotic receptor mediated phenomena. 47. Novel C4a- and N-substituted-1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-6-ols Bioorganic and Medicinal Chemistry 21(11): 3298-3309
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Iyer, M.R.; Lee, Y.S.; Deschamps, J.R.; Rothman, R.B.; Dersch, C.M.; Jacobson, A.E.; Rice, K.C. 2010: Probes for narcotic receptor mediated phenomena. 40. N-substituted cis-4a-ethyl-1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-8-ols Bioorganic and Medicinal Chemistry 18(1): 91-99
Iyer, M.R.; Rothman, R.B.; Dersch, C.M.; Jacobson, A.E.; Rice, K.C. 2015: Probes for narcotic receptor mediated phenomena 49. N-substituted rac-cis-4a-arylalkyl-1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-6-ols European Journal of Medicinal Chemistry 92: 531-539
Lim, H.J.; Dersch, C.M.; Rothman, R.B.; Deschamps, J.R.; Jacobson, A.E.; Rice, K.C. 2013: Probes for narcotic receptor mediated phenomena. 48. C7- and C8-substituted 5-phenylmorphan opioids from diastereoselective alkylation European Journal of Medicinal Chemistry 67: 335-343
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