Abstract
We have developed a new approach to prodrugs, which utilizes a pH-induced intramolecular O-->N migration of an acyloxy group in carbonate moiety to a free amino moiety at neutral pH. This method is exemplified by facile rearrangement of highly water-soluble prodrug 3 to carbamate 4, a close analogue of HIV-1 protease inhibitor Amprenavir. The O-->N acyloxy migration is unprecedented in the context of prodrugs and it enables a high atom economy due to recycling of the 'pro' moiety.
MeSH terms
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Carbamates
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Chemical Phenomena
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Chemistry, Physical
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Furans
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HIV Protease Inhibitors / chemistry
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HIV Protease Inhibitors / pharmacology*
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HIV-1 / drug effects*
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Hydrogen-Ion Concentration
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Indicators and Reagents
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Kinetics
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Magnetic Resonance Spectroscopy
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Prodrugs / chemistry
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Prodrugs / pharmacology*
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Solubility
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Structure-Activity Relationship
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Sulfonamides / chemistry
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Sulfonamides / pharmacology*
Substances
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Carbamates
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Furans
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HIV Protease Inhibitors
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Indicators and Reagents
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Prodrugs
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Sulfonamides
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amprenavir