These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Relationships between the structure of 6-allyl-6,8-diazabicyclo[3.2.2]nonane derivatives and their sigma receptor affinity and cytotoxic activity.
    Author: Holl R, Schepmann D, Grünert R, Bednarski PJ, Wünsch B.
    Journal: Bioorg Med Chem; 2009 Jan 15; 17(2):777-93. PubMed ID: 19081725.
    Abstract:
    A series of bridged piperazine derivatives was prepared and the affinity toward sigma(1) and sigma(2) receptors by means of radioligand binding assays as well as the inhibition of the growth of six human tumor cell lines was investigated. All possible stereoisomers of the 2-hydroxy, 2-methoxy, 2,2-dimethoxy, 2-oxo, and 2-unsubstituted 6,8-diazabicyclo[3.2.2]nonanes were prepared in a chiral pool synthesis starting with (S)- and (R)-glutamate. A Dieckmann analogous cyclization was the key step in the synthesis of the bicyclic framework. The configuration in position 2 was established by a diastereoselective LiBH(4) reduction and subsequent Mitsunobu inversion. Structure-affinity relationships demonstrate that substituents in position 2 decrease sigma(1) receptor affinity which might be due to unfavorable interactions with the sigma(1) receptor protein. Without a substituent in position 2 high sigma(1) affinity was obtained (23a ((+)-(1S,5S)-6-allyl-8-(4-methoxybenzyl)-6,8-diazabicyclo[3.2.2]nonane): K(i)=11 nM). Experiments with six human tumor cell lines showed a weak but selective growth inhibition of the human small cell lung cancer cell line A-427 by the methyl ethers ent-16b (IC(50)=18.9 microM), 21a (IC(50)=16.4 microM), ent-21a (IC(50)=20.4 microM), and 21b (IC(50)=27.1 microM) and the unsubstituted compounds 23a and 23b (42% inhibition at 20 microM).
    [Abstract] [Full Text] [Related] [New Search]