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Antimicrobial Agents and Chemotherapy, August 2006, p. 2857-2859, Vol. 50, No. 8
0066-4804/06/$08.00+0     doi:10.1128/AAC.01223-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Alkoxyalkyl Esters of (S)-9-[3-Hydroxy-2-(Phosphonomethoxy)Propyl]Adenine Are Potent Inhibitors of the Replication of Wild-Type and Drug-Resistant Human Immunodeficiency Virus Type 1 In Vitro

Department of Medicine, Division of Infectious Disease, University of California, San Diego, and Veterans Medical Research Foundation, La Jolla, California

Received 19 September 2005/ Returned for modification 9 November 2005/ Accepted 8 May 2006

(S)-9-[3-Hydroxy-2-(phosphonomethoxy)propyl]adenine [(S)-HPMPA], is an effective broad-spectrum antiviral against many DNA viruses but has been reported to be inactive against human immunodeficiency virus (HIV). We synthesized several alkoxyalkyl esters of (S)-HPMPA and now report that hexadecyloxypropyl-(S)-HPMPA [HDP-(S)-HPMPA] and octadecyloxyethyl-(S)-HPMPA [ODE-(S)-HPMPA]had 50% effective concentrations of 0.4 to 7.0 nanomolar and were nearly fully active against HIV variants having reverse transcriptase mutations M184V and K103N and against a zidovudine-resistant variant with mutations D67N, K70R, T215Y, and K219Q. Resistance to HDP-(S)-HPMPA and ODE-(S)-HPMPA was noted for a mutant with mutation K65R. HDP-(S)-HPMPA is also active against herpes simplex virus type 1, human cytomegalovirus, hepatitis B virus, adenoviruses, and orthopoxviruses and is worthy of further evaluation as a possibly therapy for HIV infection.

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