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Ethyl malonate amides: a diketo acid offspring fragment for HIV integrase inhibition
Katarzyna Serafin1, Pawel Mazur, Andrzej Bak
1Institute of Chemistry, University of Silesia, PL-40006 Katowice, Poland.
Abstract:
While searching for new HIV integrase inhibitors we discovered that some ethyl malonate amides (EMA) are active against this enzyme. Surprisingly, the main function can only very rarely be found among the reported drug candidates. We synthesised a series of compounds in order to establish and analyse the structure-activity relationship. The similarity to the important classes of HIV integrase inhibitors as well as the synthetic availability of the different targets including this pharmacophore makes EMA compounds an interesting object of investigations.
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The DCC-promoted synthesis of amides begins with the protonation of DCC by carboxylic acid. The protonation makes it a better acceptor. Next, the addition of carboxylate to the protonated carbodiimide gives a reactive acylating agent.
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Next, the second equivalent of amine serves as a Brønsted base and deprotonates the quaternary amide...

