960599-34-2Relevant academic research and scientific papers
Synthesis of bicyclic σ receptor ligands with cytotoxic activity
Geiger, Christian,Zelenka, Christel,Weigl, Manuela,Fr?hlich, Roland,Wibbeling, Birgit,Lehmkuhl, Kirstin,Schepmann, Dirk,Grünert, Renate,Bednarski, Patrick J.,Wünsch, Bernhard
, p. 6144 - 6153 (2008/09/16)
All possible stereoisomeric alcohols (6-benzyl-8-(4-methoxybenzyl)-6,8- diazabicyclo[3.2.2]nonan-2-ol) and methyl ethers (6-benzyl-2-methoxy-8-(4- methoxybenzyl)-6,8-diazabicyclo[3.2.2]nonane) are prepared from (R)- and (S)-glutamate. A Dieckmann analogous cyclization, which makes use of trapping the primary cyclization product with Me3SiCl, generates the bicyclic framework. Stereoselective LiBH4 reduction and Mitsunobu inversion establish the configuration in position 2. Enantiomeric alcohols 15 (1S,2S,5R) and ent-15 (1R,2R,5S) as well as diastereomeric methyl ethers ent-17 (1R,2R,5S) and ent-22 (1R,2S,5S) display high σ1 receptor affinity. Cell growth inhibition of the stereoisomeric alcohols and methyl ethers against five human tumor cell lines is investigated. In particular, at a concentration of 20 μthe four methyl ethers stop completely the cell growth of the small cell lung cancer cell line A-427, indicating a specific target in this cell line. The IC50-values of methyl ethers ent-17 and ent-22 are in the range of the antitumor drugs cisplatin and oxaliplatin. Binding assays show that the investigated tumor cell lines express considerable amounts of σ1 and σ2 receptors.
