Suksdorfin analogs, compositions thereof, and methods for making and using thereof
AssigneesThe University of North Carolina at Chapel Hill, Panacos Pharmaceuticals, Inc.
InventorsKuo-Hsiung Lee, Yoshiki Kashiwada, Li Huang, Thomas Tung-Ying Lee, Mark Cosentino, Jim Snider, Mark Manak, Lan Xie
Life of this patent
Estimating the term…
Abstract
The present invention is directed to compounds that are analogs of the natural product suksdorfin. Compounds of the present invention include those having Formula IV: wherein R20 through R26, M and Z are defined herein. The invention is also directed to pharmaceutical compositions and methods of using these compositions for treating retroviral infections.
Claims18
A compound according to formula (IV):
- wherein M is O or NH;
- Z is O, NH or S;
- R20, R21, R22, R23, R24, are each H, halogen, OH, O-alkyl, O-acyl, NH2, NH-alkyl, N-(alkyl)2, CF3, OCF3 or CH2CONH-alkyl;
- R25 and R26 are each H, C1-10 alkyl, C1-10acyl, aryl, COCF3, amide or CH3COOR26, where R16 is C1-10alkyl, C1-10acyl, or aryl or (+) - camphanoyl or (−) -camphanoyl;
- wherein the bond between C3 and C4 can be double or single;
- configurations at 3′ or 4′ can be (R) or (S);
- and R25 and R26 can be oriented cis-β or cis-α, or trans-3′-β or trans-3′-α.
A compound according to formula (V):
- wherein M is O or NH;
- X and Z═O, NH or S;
- R28, R29, R30, R31 and R32 are each H, halogen, OH, O-alkyl, O-acyl, NH2, NH-alkyl, N-(alkyl)2, CF3, OCF3 or CH2CONH-alkyl;
- R33 and R34 are each H, C1-10 alkyl, C1-10acyl, aryl, COCF3, amide or CH2COO R35, where R35 is C1-10 alkyl, C1-10 acyl, or aryl or (+) -camphanoyl or (−) -camphanoyl and where the bond between C3 and C4 can be double or single;
- configurations at 3′ or 4′ can be (R) or (S);
- and R33 and R34 can be oriented cis-β or cis-α or trans-3′-β or trans-3′-α.
A compound having the formula:
- wherein
- M is O or NH;
- X and Z are O;
- Y is O, NH or S;
- R13, R15 and R16 are independently hydrogen, halogen, hydroxy, alkoxy, acyloxy, amino, monoalkylamino, dialkylamino, trifluoromethyl, trifluoromethoxy or —CH2CONH-alkyl;
- R14 is hydrogen, halogen, hydroxy, alkyl, alkoxy, acyloxy, amino, monoalkylamino, dialkylamino, trifluoromethyl, trifluoromethoxy or —CH2CONH-alkyl;
- R17 and R18 are independently hydrogen, C1-10 alkyl, C1-10 acyl, camphanoyl, aryl, trifluoromethylcarbonyl, amide or —CH2COOR19, where R19 is C1-10 alkyl or aryl;
- and
- where the configurations at 3′ or 4′ can be (R) or (S);
- and R17 and R18 can be oriented cis-β cis-α, trans-3′-β or trans-3′-α;
- with the proviso that
- when M, X, Y and Z are each O and R13, R14, R15 and R16 are each hydrogen,
- then R17 or R18 are each other than hydrogen, C1-10 acyl or C1-10 alkyl.
A method for inhibiting a retroviral infection in cells or tissue of an animal, comprising administering an effective retroviral inhibiting amount of a compound according to formula (III):
- wherein
- M is O or NH;
- X and Z are O;
- Y is O, NH or S;
- R13, R15 and R16 are independently hydrogen, halogen, hydroxy, alkoxy, acyloxy, amino, monoalkylamino, dialkylamino, trifluoromethyl, trifluoromethoxy or —CH2CONH-alkyl;
- R14 is hydrogen, halogen, hydroxy, alkyl, alkoxy, acyloxy, amino, monoalkylamino, dialkylamino, trifluoromethyl, trifluoromethoxy or —CH2CONH-alkyl;
- R17 and R18 are independently hydrogen, C1-10 alkyl, C1-10 acyl, camphanoyl, aryl, trifluoromethylcarbonyl, amide, or —CH2COOR9, where R19 is C1-10 alkyl or aryl, and
- where the configurations at 3′ or 4′ can be (R) or (S);
- and R17 and R18 can be oriented cis-β, cis-α, trans-3′-β or trans-3′-α.
A method for treating a patient suffering from a retroviral related pathology, comprising administering to said patient an effective retroviral inhibiting amount of a compound according to formula (Ill):
- wherein
- M is O or NH;
- X and Z are O;
- Y is O, NH or S;
- R13, R15 and R16 are independently hydrogen, halogen, hydroxy, alkoxy, acyloxy, amino, monoalkylamino, dialkylamino, trifluoromethyl, trifluoromethoxy or CH2CONH-alkyl;
- R14 is hydrogen, halogen, hydroxy, alkyl, alkoxy, acyloxy, amino, monoalkylamino, dialkylamino, trifluoromethyl, trifluoromethoxy or —CH2CONH-alkyl;
- R17 and R18 are independently hydrogen, C1-10 alkyl, C1-10 acyl, aryl, trifluoromethylcarhonyl, carbamoyl, camphanoyl, or —CH2COOR19, where R19 is C1-10 alkyl or aryl;
- and
- where the configurations at 3′ or 4′ can be (R) or (S);
- and R17 and R18 can be oriented cis-β, cis-α, trans-3′-β or trans-3′-α.
Dependencies are inferred from the claim text.