Phosphonates with reduced toxicity for treatment of viral infections

摘要

There are provided, inter alia, acyclic nucleoside phosphonate compounds having reduced toxicity and enhanced antiviral activity, and pharmaceutically accepted salts and solvates thereof. There are also provided methods of using the disclosed compounds for inhibiting viral RNA-dependent RNA polymerase, inhibiting viral reverse transcriptase, inhibiting replication of virus, including hepatitis C virus or a human retrovirus, and treating a subject infected with a virus, including hepatitis C virus or a human retrovirus.

主权项

1. A compound having the structure of Formula (I): wherein
BN is a substituted or unsubstituted nucleobase;L1 is a bond or —O—;R1 is halogen, —CF3, unsubstituted alkyl, substituted or unsubstituted cycloalkyl, or substituted or unsubstituted aryl;provided that, if L1 is a bond, then R1 is halogen, and if L1 is —O—, then R1 is —CF3, unsubstituted alkyl, substituted or unsubstituted cycloalkyl, or substituted or unsubstituted aryl;R2 is
L2-O—R3  (II),wherein L2 is a substituted or unsubstituted alkylene, substituted or unsubstituted cycloalkylene, or substituted or unsubstituted arylene; andR3 is substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, or substituted or unsubstituted aryl;or pharmaceutically accepted salt or solvate thereof.