US 7,547,704 B2
Modified 2′ and 3′-nucleoside prodrugs for treating Flaviviridae infections
Paola LaColla, Cagliari (Italy); Richard Storer, Folkstone (United Kingdom); Gilles Gosselin, Monpellier (France); and Jean-Pierre Sommadossi, Cambridge, Mass. (US)
Assigned to Idenix Pharmaceuticals, Inc., Cambridge, Mass. (US); Centre National de la Recherche Scientifique, Paris (France); and Universita Degli Studi di Cagliari, Cagliari (Italy)
Filed on Dec. 06, 2004, as Appl. No. 11/5,467.
Application 11/005467 is a continuation of application No. 10/608907, filed on Jun. 27, 2003.
Claims priority of provisional application 60/392350, filed on Jun. 28, 2002.
Claims priority of provisional application 60/466194, filed on Apr. 28, 2003.
Claims priority of provisional application 60/470949, filed on May 14, 2003.
Prior Publication US 2007/0042940 A1, Feb. 22, 2007
Int. Cl. A01N 43/04 (2006.01); A01N 43/54 (2006.01); C07D 239/00 (2006.01); C07D 239/02 (2006.01)
U.S. Cl. 514—256  [514/49; 544/242; 544/298; 544/309; 544/315; 536/28.1; 536/28.4] 40 Claims
 
1. A compound of Formula (VI):

OG Complex Work Unit Drawing
or a pharmaceutically acceptable salt thereof, wherein:
R1 is H; phosphate; acyl; an amino acid ester; a carbohydrate; a peptide; or pharmaceutically acceptable leaving group which when administered in vivo provides a compound wherein R1 is H or phosphate;
R2 is acyl; an amino acid ester; a carbohydrate; a peptide; or a pharmaceutically acceptable leaving group which when administered in vivo provides a compound wherein R2 is H
Base is selected from the group consisting of

OG Complex Work Unit Drawing
each R4 and R5 is independently hydrogen, acyl, alkyl, lower alkyl, alkenyl, alkynyl or cycloalkyl;
X is CH2, CHF, CF2, C(Y3)2, CHCN, C(CN)2, CHR4 or C(R4)2;
X2 is H, straight chained, branched or cyclic alkyl, CH3, CF3, or fluoro;
X3 is H or CH3;
Y3 is H, F, Cl, Br or I;
R6 is alkyl, CF3, alkenyl, or alkynyl;
R7 is OH, O(acyl), or halo;
R8 and R11 are hydrogen;
R9 is OH or OR2;
R10 is hydrogen; and
wherein each alkyl is optionally substituted with one or more substituents selected from the group consisting of fluoro, chloro, bromo, iodo, hydroxyl, amino, alkylamino, arylamino, alkoxy, aryloxy, nitro, cyano, sulfonic acid, sulfate, phosphonic acid, phosphate, and phosphonate.