6-Substituted Derivatives of Carbovir: Anti-HIV Activity |
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| Authors: | Robert Vince John Kilama Phuong T Pham Scott A Beers Bonnie J Bowdon Kathy A Keith |
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| Institution: | 1. Department of Medicinal Chemistry , College of Pharmacy 308 Harvard St. S. E. University of Minnesota , Minneapolis, MN, 55455-0343;2. Southern Research Institute , 2000 Ninth Avenue South, Birmingham, AL, 35255-5305 |
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| Abstract: | Abstract A series of 6-alkoxy and 6-alkylamino carbovir derivatives were synthesized in order to evaluate prodrug approaches to increased bioavailability of the anti-HIV agent, carbovir. All of the compounds were active against HIV with the N-alkyl derivatives less active than the corresponding O-alkyl derivatives. The adenosine deaminase inhibitor, EHNA, had no effect on the anti-HIV activity of 6-propoxycarbovir, while the adenylic acid deaminase inhibitor, 2′-deoxycoformycin, significantly decreased antiviral activity. These observations suggest that the 6-alkoxycarbovirs are metabolized directly to the monophosphates and are subsequently converted to carbovir monophosphate via adenylic acid deaminase |
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