Novel polygodial analogs for the treatment of cancer and other proliferative diseases
OwnerCara B. GONZALES, Alexander KORNIENKO +1inventors
InventorsCara B. GONZALES, Alexander KORNIENKO, Ramesh DASARI
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Abstract
The present disclosure relates generally to derivatives of polygodial and methods of use thereof. In some aspects, the present disclosure relates to using polygodial derivatives to treat cancer or other hyperproliferative diseases.
Claims31
A compound of the formula:
- wherein:
- X is an electron-withdrawing group;
- R1 is hydrogen or alkyl(C≤12), cycloalkyl(C≤12), or a substituted version of either of these groups;
- R2 is acyl(C≤12) or substituted acyl(C≤12);
- R3 is hydrogen, alkyl(C≤12), cycloalkyl(C≤12), substituted alkyl(C≤12) or substituted cycloalkyl(C≤12);
- R4 and R5 are each independently hydrogen, alkyl(C≤12), cycloalkyl(C≤12), substituted alkyl(C≤12) or substituted cycloalkyl(C≤12);
- or R4 and R5 are taken together and are alkanediyl(C≤8) or substituted alkanediyl(C≤8);
- R6 is amino, cyano, halo, hydroxy, or nitro;
- alkyl(C≤6), cycloalkyl(C≤6), acyl(C≤6), alkoxy(C≤6), acyloxy(C≤6), amido(C≤6), or a substituted version of any of these groups;
- and
- n is 0, 1, 2, 3, or 4;
- or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof.
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10-11. (canceled)
13-27. (canceled)
A compound of the formula:
- wherein:
- R7 is hydrogen or alkyl(C≤12), aralkyl(C≤12), or a substituted version of either of these groups;
- and
- R8 is hydrogen, alkyl(C≤12), or substituted alkyl(C≤12);
- or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof.
29-31. (canceled)
33-34. (canceled)
A pharmaceutical composition comprising:
- (a) polygodial, epi-polygodial, or a stereoisomer thereof;
- and
- (b) a pharmaceutically acceptable excipient;
- formulated for administration by injection to a tumor.
39-50. (canceled)
52-53. (canceled)
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58-60. (canceled)
A method of preparing a compound of formula I comprising reacting a compound of the formula:
- wherein:
- R2 is acyl(C≤12) or substituted acyl(C≤12);
- R3 is hydrogen, alkyl(C≤12), cycloalkyl(C≤12), substituted alkyl(C≤12) or substituted cycloalkyl(C≤12);
- R4 and R5 are each independently hydrogen, alkyl(C≤12), cycloalkyl(C≤12), substituted alkyl(C≤12) or substituted cycloalkyl(C≤12);
- or R4 and R5 are taken together and are alkanediyl(C≤8) or substituted alkanediyl(C≤8);
- R6 is amino, cyano, halo, hydroxy, or nitro;
- alkyl(C≤6), cycloalkyl(C≤6), acyl(C≤6), alkoxy(C≤6), acyloxy(C≤6), amido(C≤6), or a substituted version of any of these groups;
- and
- n is 0, 1, 2, 3, or 4;
- with a compound of the formula:
- wherein:
- A− is a monovalent anion;
- X is an electron-withdrawing group;
- R1 is hydrogen or alkyl(C≤12), cycloalkyl(C≤12), or a substituted version of either of these groups;
- and
- R7, R7′, and R7″ are each independently aryl(C≤12) or substituted aryl(C≤12);
- in the presence of a base.
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Dependencies are inferred from the claim text.