Extension of the Nenitzescu reaction to simple ketones provides an efficient route to 1′-alkyi-5′-hydroxynaltrindole analogues, potent and selective δ-opioid receptor antagonists

Journal of Medicinal Chemistry

Volumn 48, Issue 2, 2005, Pages 635-638

  Shefali, ^a   Srivastava, Sanjay K ^a   Husbands, Stephen M ^a   Lewis, John W ^a  

^a University of Bath   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

1 ALKYL 5 HYDROXYNALTRINIDOLE; 1 BENZYL 17 CYCLOROPROPYLMETHYL 6,7 DIDEHYDRO 4,5ALPHA EPOXY 3,14,5 TRIHYDROXYINDOLO 2,3 6,7 MORPHINAN; 17 ALLYL 1 BENZYL 6,7 DIDEHYDRO 4,5ALPHA EPOXY 3,14,5 TRIHYDROXYINDOLO 2,3 6,7 MORPHINAN; 3,1 DIBENZYL 17 CYCLOPROPYLMETHYL 6,7 DIDEHYDRO 4,5ALPHA EPOXY 14,5 DIHYDROXYINDOLO 2,3 6,7 MORPHINAN; 5 HYDROXYINDOLE; BENZOQUINONE; IMINE; KETONE; MORPHINAN DERIVATIVE; MU OPIATE RECEPTOR; MU OPIATE RECEPTOR ANTAGONIST; NALOXONE; NALTREXONE; NALTRINDOLE; UNCLASSIFIED DRUG;

ANIMAL CELL; ARTICLE; BINDING AFFINITY; BINDING ASSAY; CHEMICAL REACTION; CHEMICAL STRUCTURE; CHO CELL; COLUMN CHROMATOGRAPHY; DRUG BINDING; DRUG POTENCY; DRUG SELECTIVITY; DRUG STRUCTURE; NENITZESCU REACTION; NONHUMAN;

ANIMALS; CHO CELLS; CRICETINAE; CRICETULUS; HUMANS; ISOMERISM; KETONES; NALTREXONE; RADIOLIGAND ASSAY; RECEPTORS, OPIOID, DELTA;

EID: 12344299375     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm040853s     Document Type: Article

References (12)

1. Brase, S.; Gil, C.; Knepper, K. The recent impact of solid-phase synthesis on medicinally relevant benzoannelated nitrogen heterocycles. Bioorg. Med. Chem. 2002, 10, 2415-2437.
2. Kinugawa, M.; Arai, H.; Ogasa, T.; Kasai, M. Development of large-scale synthetic process for antitumor agent EO9. J. Synth. Org. Chem. Jpn. 1999, 57, 401-406.
3. Pawlak, J. M.; Khau, V. V.; Hutchison, D. R.; Martinelli, M. J. A practical, Nenitzescu-based synthesis of LY311727, the first potent and selective s-PLA(2) inhibitor. J. Org. Chem. 1996, 61, 9055-9059.
4. Patrick, J. B.; Saunders, E. K. Studies on the Nenitzescu synthesis of 5-hydroxyindoles. Tetrahedron Lett. 1979, 42, 4009-4012.
5. Allen Jr., G. R.; Pidacks, C.; Weiss, M. J. The mitomycin antibiotics. Synthetic studies. XIV. The Nenitzescu indole synthesis. Formation of isomeric indoles and reaction mechanism. J. Am. Chem. Soc. 1966, 88, 2536-2544.
6. Portoghese, P. S.; Sultana, M.; Takemori, A. E. Design of peptidomimetic delta-opioid receptor antagonists using the message-address concept. J. Med. Chem. 1990, 33, 1714-1720.
7. Srivastava, S. K.; Shefali, Miller, C. N.; Aceto, M. D.; Traynor, J. R.; Lewis, J. W.; Husbands, S. M. Effects of substitution on the pyrrole N-atom in derivatives of tetrahydronaltrindole, tetrahydrooxymorphindole and a related 4,5-epoxyphenylpyr-rolomorphinan. J. Med. Chem. 2004, 47, 6645-6648.
8. Srivastava, S. K.; Husbands, S. M.; Traynor, J. R.; Lewis, J. W. 4′-Arylpyrrolomorphinans: Effect of a pyrrolo-N-benzyl substituent in enhancing δ-opioid antagonist activity. J. Med. Chem. 2002, 45, 537-540.
9. Shefali; Srivastava, S. K.; Hall, L. D.; Lewis, J. W.; Husbands, S. M. Michael reactions of benzylimines of morphinan-6-ones: Synthesis of pyrrolo- and pyridinomorphinans. Helv. Chim. Acta 2002, 85, 1790-1799.
10. Meyer, H. Heterocycles from nitroalkenes. 1. Pyrroles via Michael addition of enamines. Leibigs Ann. Chem. 1981, 1534-1544.
11. Toll, L., Berzetei-Gurske, I. P., Polgar, W. E., Brandt, S. R., Adapa, I. D., Rodriguez, L., Schwartz, R. W., Haggart, D., O'Brien, A., White, A., Kennedy, J. M., Craymer, K, Farrington, L., and Auh, J. S. Standard binding and functional assays related to (NIDA) medications development division testing for potential cocaine and narcotic treatment programs. NIDA Res. Monogr. 1998, 178, 440-466.
12. Farouz-Grant, F.; Portoghese, P. S. Pyrrolomorphinans as opioid receptor antagonists. The role of steric hindrance in conferring selectivity. J. Med. Chem. 1997, 40, 1977-1981.