Final Report Summary - ANTCARD (Analogues Of Thromboxane For The Treatment Of Cardiovascular Disease)
Therefore, synthetic work on an analogue of TxA2 via a novel short synthesis for the synthesis of PGF2α [6] has been done.
The aim of the project is the synthesis of thromboxanes and their analogues as well as their biological and pharmacological evaluation. Within the reporting period the synthesis of the starting material has been optimised and kinetic studies of the key step, the domino-aldol reaction, have been performed using NMR to achieve reliable results and to get a better understanding of the reaction itself. Introduction of the side chain via the literature known route as well as development of a new route to introduce the lower side chain of the molecule has been investigated. Beside its use for the synthesis of thromboxanes the optimisation and the new introduction of the lower side chain can be used in the synthesis of prostaglandins, which are also a very important class of natural products. Optimisation of the aldol process is therefore of academic and industrial interest, since the so far used route towards prostaglandin based drugs are very long and expensive [7].
The expected final result is the development of new drugs to treat cardiovascular diseases as an alternative to the standard medication like Aspirin or clopidogrel. Therefore, the synthesis of new thromboxane derivatives are necessary, which are still under development.
The impact of this project is the synthesis of active thromboxanes via an economical and ecologically friendly process to develop new drugs, which could lead to treatment of cardiovascular diseases. Since cardiovascular diseases occupy the first and the second place in the top ten causes of death worldwide it is beyond doubt that the development of new drug treatments for cardiovascular diseases is extremely important and of a high societal impact for the European Research Area (ERA). In 2012 47% of all deaths in the Europe were caused by cardiovascular diseases. In summary, the project has a very high societal impact, relevant to the ERA and beyond. It could lead to important new approaches to cardiovascular disease which will have a major impact on the pharmaceutical industry as well.
Literature:
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[5] H. J. Ting, J. P. Murad, E. V. P. Espinosa, F. T. Khasawneh, Journal of Cardiovascular Pharmacology and Therapeutics 2012, 17, 248–259.
[6] a) G. Coulthard, W. Erb, V. K. Aggarwal, Nature 2012, 489, 278–281; b) V. K. Aggarwal, G. Coulthard, W. Erb, International Patent Application No. PCT/GB2013/051532, 2013.
[7] E. J. Corey, N. M. Weinshenker, T. K. Schaaf, W. Huber, J. Am. Chem. Soc. 1969, 91, 5675–5677.