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Medicinal Chemistry of HIV Integrase InhibitorsMedicinal Chemistry of HIV Integrase Inhibitors
When AIDS was first discovered in the 1980s, an individual's prognosis was grim, with a life expectancy on the order of 10 years. With development of effective antiviral drugs, this has increased up to 50 years or more. The HIV virus encodes several enzymes that are drug targets. The first effective drugs that were developed inhibit reverse transcriptase. The next drugs that were developed inhibit another enzymes that the virus encodes, HIV protease. The drugs that are under consideration here, the HIV integrase inhibitors are the most recently available class. Using multiple classes of drugs in combination has turned out to be a vital factor in effective treatment of HIV infection. For this reason, new integrase inhibitors have been avidly pursued by medicinal chemists across the globe.
Some of the first experimental compounds that were developed were members of a class called β-diketo acids, since there are 2 carbonyl groups located beta to a carboxylic acid functional group. Although they are referred to as "diketo acids", in solution they can also exist as the tautomeric enols.
The structure to the left is the first HIV integrase that has made it's way to market, raltegravir (Isentress). |
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