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.

Abstract

Cis-Octahydro-14H-benzo[g]quinolino[2,3-a]quinolidines 6 were obtained in 6 steps from L-phenylalanine. The key step utilizes a diastereoselective intramolecular EtAlCl2-catalyzed hetero-Diels-Alder reaction. Compounds 6a-f were tested in vitro against human medulloblastoma D283 Med and glioblastoma A-172 and T98G cell lines and showed improved cytotoxicity compared to the corresponding, less rigid pyrido[1,2-b]isoquinolines 1.

• Authors: A Monsees, S Laschat, M Hotfilder, P G Jones
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 8 Issue 20 Pg. 2881-4 (Oct 20 1998) ISSN: 0960-894X [Print] England
• PMID: 9873641 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Quinolines

Topics

• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Brain Neoplasms (pathology)
• Cell Line
• Drug Screening Assays, Antitumor
• Humans
• Inhibitory Concentration 50
• Quinolines (chemical synthesis, chemistry, pharmacology)
• Structure-Activity Relationship
• Tumor Cells, Cultured