Anti-flavivirus therapeutic
AssigneesHealth Research, Inc., Regents of the University of Minnesota
InventorsPei-Yong Shi, Francesc Puig-Basagoiti, Krzysztof W. Pankiewicz, Krzysztof Felczak, Liqiang Chen
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Abstract
The present invention relates to anti-flavivirus compounds, including lycorine and derivatives thereof, and their use in treating a subject infected by a flavivirus. The present invention also relates to the use of the anti-flavivirus compounds for the prophylaxis of flavivirus infection. The present invention further relates to a method of suppressing viral RNA synthesis of a flavivirus. Also described is a method of preparing an anti-flavivirus compound for use in the treatment or prophylaxis of flavivirus infection.
Claims21
A method of treating a subject infected by a flavivirus, said method comprising:
- administering to said subject infected by a flavivirus an effective amount of a compound of the structure (I), (II), or (III), or a pharmaceutically acceptable salt of said compound, optionally in combination with a pharmaceutically acceptable excipient, carrier, or additive, wherein structures (I), (II), and (III) are as follows:
- wherein:
- Y and Z are each independently selected from the group consisting of H, alkyl, aralkyl, alkoxyalkyl, heteroalkyl, alkenyl, acyl, alkylsilyl, and arylalkylsilyl;
- or
- Y and Z together are alkylidenyl or aralkylidenyl.
A method of preventing a flavivirus infection in a subject, said method comprising:
- administering to said subject an effective amount of a compound of the structure (I), (II), or (III), or a pharmaceutically acceptable salt of said compound, optionally in combination with a pharmaceutically acceptable excipient, carrier, or additive, wherein structures (I), (II), and (III) are as follows:
- wherein:
- Y and Z are each independently selected from the group consisting of H, alkyl, aralkyl, alkoxyalkyl, heteroalkyl, alkenyl, acyl, alkylsilyl, and arylalkylsilyl;
- or
- Y and Z together are alkylidenyl or aralkylidenyl.
A method of suppressing viral RNA synthesis of a flavivirus, said method comprising:
- providing a compound of the structure (I), (II), or (III) as follows:
- wherein:
- Y and Z are each independently selected from the group consisting of H, alkyl, aralkyl, alkoxyalkyl, heteroalkyl, alkenyl, acyl, alkylsilyl, and arylalkylsilyl;
- or
- Y and Z together are alkylidenyl or aralkylidenyl;
- and
- contacting said flavivirus with an effective amount of said compound to suppress the viral RNA synthesis of said flavivirus.
A method for preparing an anti-flavivirus compound for use in the treatment or prophylaxis of a flavivirus infection in a subject, said method comprising:
- providing a lycorine compound having a structure of:
- or a precursor of said compound;
- and
- substituting the hydroxyl group at position 1 and/or at position 2 with a protecting group in order to yield an anti-flavivirus agent having a therapeutic index (TI) of 10 or greater, wherein said therapeutic index comprises the ratio of CC50 (uM)/EC50 (uM).
An anti-flavivirus compound having a structure of:
Dependencies are inferred from the claim text.