Diastereoselective synthesis of octahydro-14H-benzo[g]quinolino[2,3- a]quinolidines. Improved cytotoxic activity against human brain tumor cell lines as a result of the increased rigidity of the molecular backbone

Bioorganic and Medicinal Chemistry Letters

Volumn 8, Issue 20, 1998, Pages 2881-2884

  Monsees, Axel ^a   Laschat, Sabine ^a   Hotfilder, Marc ^b   Jones, Peter G ^a  

^a TECHNICAL UNIVERSITY OF BRAUNSCHWEIG   (Germany)

^b UNIVERSITY OF MÜNSTER   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; OCTAHYDRO 14H BENZO[G]QUINOLINO[2,3 A]QUINOLIDINE; PYRIDO[1,2 B]ISOQUINOLINE; UNCLASSIFIED DRUG;

ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER CELL CULTURE; CYTOTOXICITY; DRUG CONFORMATION; DRUG SYNTHESIS; HUMAN; HUMAN CELL; MEDULLOBLASTOMA; STEREOCHEMISTRY;

ANTINEOPLASTIC AGENTS; BRAIN NEOPLASMS; CELL LINE; DRUG SCREENING ASSAYS, ANTITUMOR; HUMANS; INHIBITORY CONCENTRATION 50; QUINOLINES; STRUCTURE-ACTIVITY RELATIONSHIP; TUMOR CELLS, CULTURED;

EID: 0032552845     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(98)00506-X     Document Type: Article

References (17)

1. 1. Nicolaou, K. C.; Dai, W.-M.; Guy, R. K. Angew. Chem. 1994, 106, 38; Angew. Chem. Int. Ed. Engl. 1994, 33, 15.
2. 1. Nicolaou, K. C.; Dai, W.-M.; Guy, R. K. Angew. Chem. 1994, 106, 38; Angew. Chem. Int. Ed. Engl. 1994, 33, 15.
3. 2. Sundquist, W. I.; Lippard, S. J. Coord. Chem. Rev. 1990, 100, 293.
4. 3. Potmesil, M.; Pinedo, H. (eds.) Camptothecins: New Anticancer Agents, CRC Boca Raton, FL, 1995.
5. 4. Luzzio, M. J.; Besterman, J. M.; Emerson, D. L.; Evans, M. G.; Lackey, K.; Leitner, P. L.; McIntyre, G.; Morton, B.; Myers, P. L.; Peel, M.; Sisco, J. M.; Sternbach, D. D.; Tong, W.-Q.; Truesdale, A.; Uehling, D. E.; Vuong, A.; Yates, J. J. Med. Chem. 1995, 38, 395.
6. 5. Plate, K. H.; Risal, W. Glia 1995, 15, 339 and references cited therein.
7. 6. Monsees, A.; Laschat, S.; Hotfilder, M.; Wolff, J.; Bergander, K.; Terfloth, L.: Fröhlich, R. Bioorg. Med. Chem. Lett. 1998, 7, 2945.
8. 7. Linkert, F.; Laschat, S.; Kotila, S.; Fox, T. Tetrahedron 1996, 52, 955.
9. 8. Linkert, F.; Laschat, S.; Knickmeier, M. Liebigs Ann. Chem. 1995, 985.
10. 9. Monsees, A.; Laschat, S.; Kotila, S.; Fox, T.; Würthwein, E. U. Liebigs Ann./Recueil 1997, 533.
11. 10. For details of the mechanism see: ref. [7].
12. 1H NMR spectra of the crude products the minor diastereomer has the all-trans-configuration. GC analysis of the reaction mixtures showed complete conversion of 5 to the cis-producl 6 and the corresponding trans-diastereomer.
13. 2 O 348.2202, found 348.2200.
14. 13. All new compounds gave satisfactory analytical and spectroscopic data.
15. -3. Data were collected on a Stoe STADI-4 diffractomcter. Programs used SHELXS-86. SHELXL-93. Full details of the crystal structure (except structure factors) have been deposited at the Cambridge Crystallographic Data Centre, and can be obtained free of charge from the Director, CCDC, 12 Union Road, Cambridge, CB2 1EZ, England, [Fax: Int.+44 - 1223-336033; e-mail: deposit@chemcrys.cam.ac.uk] on quoting the reference number 101871.
16. 15. Cytotoxicity tests were carried out as described in ref. [6].
17. 16. Hansen, M. B.; Nielsen. S. E.; Berg, K. R. J. Immunol. Methods 1989, 119, 203.