University of Southern California

Ivan S Krylov

Charles E McKenna

Boris A Kashemirov

Valeria M Zakharova

Michaela Serpi

John Hilfinger

Larryn W Peterson

An amino acid conjugate of a cyclic or acyclic nucleoside phosphonate is provided. In some cases, the amino acid conjugate is a tyrosine alkyl amide phosphonate ester conjugate of a cyclic or acyclic nucleoside phosphonate, and is useful as an antiviral compound. In certain cases, the tyrosine conjugate includes a long chain alkyl group on the carboxamide group of the tyrosine residue. In a method of preparing an acyclic tyrosine conjugate, a tert-butyloxycarbonyl (Boc) protected tyrosine residue containing a long chain alkyl group is reacted with an acyclic nucleoside phosphonate mono-ethyl ester in the presence of benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate to produce a Boc-protected nucleoside phosphonate di-ester, and the di-ester is deethylated and deprotected to produce the tyrosine conjugate. Methods of inhibiting viral replication and methods of treating a viral infection using the amino acid conjugate are also provided.

Method to improve antiviral activity of nucleotide analogue drugs

A tyrosine-based (phosphonylmethoxyalkyl)purine or -pyrimidine conjugate is provided. In some embodiments, the conjugate includes tyrosine based amino acid or dipeptide moieties of (S)-9-(3-hydroxy-2-phosphonyl-methoxypropyl)adenine or its cytosine analog. A method of synthesizing such conjugates based on Boc-protected amino acid or dipeptides is also provided. In addition, a method of isomerizing an (S,S)-diastereoisomer to an (S,R)-diastereoisomer of an amino acid-based or dipeptide-based conjugate by a process including transesterification is provided. A method of inhibiting viral infection and a method of treating viral infection based on (phosphonylmethoxyalkyl)purine or -pyrimidine conjugates is also provided.

Tyrosine-based prodrugs of antiviral agents

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Los Angeles, CA, United States of America

Ivan S Krylov