Development of new nitrogen-containing hetero- and macrocyclic compounds as potential pharmacological agents
Funding source: Swedish Research Council - Vetenskapsrådet (VR)
Period: 1/1/08 - 12/31/10
Funding: 600000 SEK
Description:
The present proposal is directed towards construction of novel analogues of naturally occurring nitrogen-containing heterocyclic compounds to be adopted as bio-active agents especially as anti-tumor as well as anti-inflammatory active materials. In the present proposal, it is intended to utilize a natural product isatin scaffold for formation of non-stabilized azomethine ylides through decarboxylative condensation with á-amino acids and trapping the generated reactive intermediates via 1,3-dipolar cycloaddition reaction with different dipolarophiles. Utilization of exocyclic olefinic linkage containing compounds as dipolarophiles should afford directly spiropyrrolidinyl-oxindole analogues, having a skeleton of biologically active and naturally occurring spiro-alkaloids. The second theme of the proposed research deals with construction of amide linkage-containing compounds, where many of benzamide derivatives have been used as anti-inflammatory active drugs such as parsalmide, roflumilast and methotrexate. The present proposal deals with the development of synthesis of either acyclic or cyclic bisbenzamide containing analogues and screening their pharmacological as well as toxicological properties. For the most effective and promising lead compounds, the phospholipids and nucleic acid conjugates will be prepared for improving efficiency of delivery of the potential drugs and to make them more site- and target-specific.
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