US 7,524,831 B2
Treatments for Flaviviridae virus infection
Bruce A. Malcolm, Westfield, N.J. (US); Robert Palermo, New York, N.Y. (US); Xiao Tong, East Brunswick, N.J. (US); Boris Feld, New Milford, N.J. (US); and Hung Le, Rockaway, N.J. (US)
Assigned to Schering Corporation, Kenilworth, N.J. (US)
Filed on Mar. 01, 2006, as Appl. No. 11/365,008.
Claims priority of provisional application 60/658006, filed on Mar. 02, 2005.
Prior Publication US 2006/0198824 A1, Sep. 07, 2006
Int. Cl. A01N 43/04 (2006.01); A61K 31/70 (2006.01)
U.S. Cl. 514—49  [514/42; 514/43; 514/52] 26 Claims
 
1. A method for treating an infection by a virus which is a member of the Flaviviridae family of viruses, in a mammalian host, comprising administering to said host a therapeutically effective amount of a compound represented by structural formula IV

OG Complex Work Unit Drawing
or a pharmaceutically acceptable salt thereof or a pharmaceutical composition thereof which composition comprises a pharmaceutically acceptable carrier; wherein R3 and R4 are independently —OH or a pharmaceutically acceptable leaving group, wherein R5 is —OH, a straight or branched chain C9 to C24 alkylphosphate or a straight or branched chain C9 to C24 alkenylphosphate group or a pharmaceutically acceptable leaving group and wherein R1 and R2 are independently C1 to C10 alkyl or wherein R1 and R2 taken together with N form a C3 to C7 ring represented by the following structural formula:

OG Complex Work Unit Drawing
wherein n and m are independently 0, 1, 2 or 3 and Q is CH2, NR, O, S, SO or SO2; and R is independently H, C1 to C6 alkyl or C1 to C6 acyl or wherein R1 and R2, taken together with the N, are represented by the structural formula:

OG Complex Work Unit Drawing
and wherein said pharmaceutically acceptable leaving groups groups are capable of being converted to —OH, -phosphate, —F or —CH3 when the compound of structural formula IV is administered in vivo and are independently represented by structural formula

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wherein Y═H, CH3, CH3CH2—, CH3CH2CH2—, Me2CH—, Me2CH2CH2—, CH3CH2CH(Me)—, PhCH2—, HOOCCH2CH2—, HSCH2—, HOOCCH2—, MeSCH2CH2—, HOCH2—,

OG Complex Work Unit Drawing
H2N(CH2)4—, or CH3CH(OH)—, or a pharmaceutically acceptable salt thereof,
or Y, taken together with the alpha-carbon and N, form

OG Complex Work Unit Drawing
wherein the pharmaceutically acceptable leaving groups are capable of being converted to —OH, -phosphate, —F or —CH3 when the compound of structural formula IV is administered in vivo and are independently represented by a structural formula selected from the group consisting of:

OG Complex Work Unit Drawing