Manassatin compounds and methods of making and using the same
AssigneeDuke University
InventorsJiyong Hong, Mark Dewhirst, Hyoungsu Kim, Amanda C. Kasper, Eui Jung Moon, Yongho Park, Ceshea M. Wooten
Life of this patent
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Abstract
Provided are manassantin compounds and methods of using the compounds. Provided are methods of treating a disease, the method comprising administering a compound according to Formula I. Further provided are pharmaceutical compositions comprising compounds according to Formula I. Also provided are methods of inhibiting HIF-1 in a cell, the methods comprising administering to the cell a compound according to Formula I.
Claims23
A method of treating a disease, the method comprising administering to a patient in need thereof an effective amount of a compound according to Formula I:
- wherein R4, R6, R7, and R9 are independently selected from alkyl and hydrogen;
- X, Y, and Z are independently selected from the group consisting of O and NR14, wherein R13 and R14 are independently selected from the group consisting of alkyl, heteroalkyl, aryl, heteroaryl, ester, acyl, sulfonyl, heterocyclyl, amido, thioamido, acetyl, hydroxyl, amino, hydrogen, halogen, and cyano;
- R3 and R10 are independently selected from the group consisting of hydrogen, alkyl, and oxo;
- R5 and R8 are independently selected from the group consisting of substituted or unsubstituted phenyl;
- and
- R1 and R2 are independently selected from the group consisting of substituted or unsubstituted phenyl of Formula II below:
- wherein R11 and R12 are independently selected from the group consisting of heteroalkyl, hydroxyl, hydrogen, halogen, and substituted alkylaryl;
- and
- wherein the disease is selected from the group consisting of leukemia, lung cancer, colon cancer, CNS cancer, melanoma, ovarian cancer, renal cancer, liver cancer, prostate cancer, breast cancer, stroke, heart disease, arthritis, ocular neovascular diseases, inflammation, kidney disease, and anemia.
A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound according to Formula I:
- wherein R4, R6, R7, and R9 are independently selected from alkyl and hydrogen;
- X, Y, and Z are independently selected from the group consisting of O and NR14, wherein R13 and R14 are independently selected from the group consisting of alkyl, heteroalkyl, aryl, heteroaryl, ester, acyl, sulfonyl, heterocyclyl, amido, thioamido, acetyl, hydroxyl, amino, hydrogen, halogen, and cyano;
- R3 and R10 are independently selected from the group consisting of hydrogen, alkyl, and oxo;
- R5 and R8 are independently selected from the group consisting of substituted or unsubstituted phenyl;
- and
- R1 and R2 are independently selected from the group consisting of substituted or unsubstituted phenyl of Formula II below:
- wherein R11 and R12 are independently selected from the group consisting of heteroalkyl, hydroxyl, hydrogen, halogen, and substituted alkylaryl.
A compound according to Formula I:
- wherein R4, R6, R7, and R9 are independently selected from alkyl, and hydrogen;
- X, Y, and Z are independently selected from the group consisting of O and NR14, wherein R13 and R14 are independently selected from the group consisting of alkyl, heteroalkyl, aryl, heteroaryl, ester, acyl, sulfonyl, heterocyclyl, amido, thioamido, acetyl, hydroxyl, amino, hydrogen, halogen, and cyano;
- R3 and R10 are independently selected from the group consisting of hydrogen, alkyl, and oxo;
- R5 and R8 are independently selected from the group consisting of substituted or unsubstituted phenyl;
- and
- R1 and R2 are independently selected from the group consisting of substituted or unsubstituted phenyl of Formula II below:
- wherein R11 and R12 are independently selected from the group consisting of heteroalkyl, hydroxyl, hydrogen, halogen, and substituted alkylaryl.
A method of inhibiting HIF-1 in a cell, the method comprising contacting the cell with a compound according to Formula I:
- wherein R4, R6, R7, and R9 are independently selected from alkyl, and hydrogen;
- X, Y, and Z are independently selected from the group consisting of O and NR14, wherein R13 and R14 are independently selected from the group consisting of alkyl, heteroalkyl, aryl, heteroaryl, ester, acyl, sulfonyl, heterocyclyl, amido, thioamido, acetyl, hydroxyl, amino, hydrogen, halogen, and cyano;
- R3 and R10 are independently selected from the group consisting of hydrogen, alkyl, and oxo;
- R5 and R8 are independently selected from the group consisting of substituted or unsubstituted phenyl;
- and
- R1 and R2 are independently selected from the group consisting of substituted or unsubstituted phenyl of Formula II below:
- wherein R11 and R12 are independently selected from the group consisting of heteroalkyl, hydroxyl, hydrogen, halogen, and substituted alkylaryl;
- in an amount effective to inhibit the HIF-1 pathway.
A method of treating an individual with a disorder associated with increased activity of the HIF-1 pathway, the method comprising administering to the individual to treat the disorder an effective amount of a compound according to Formula I:
- wherein R4, R6, R7, and R9 are independently selected from alkyl and hydrogen;
- X, Y, and Z are independently selected from the group consisting of O and NR14, wherein R13 and R14 are independently selected from the group consisting of alkyl, heteroalkyl, aryl, heteroaryl, ester, acyl, sulfonyl, heterocyclyl, amido, thioamido, acetyl, hydroxyl, amino, hydrogen, halogen, and cyano;
- R3 and R10 are independently selected from the group consisting of hydrogen, alkyl, and oxo;
- R5 and R8 are independently selected from the group consisting of substituted or unsubstituted phenyl;
- and
- R1 and R2 are independently selected from the group consisting of substituted or unsubstituted phenyl of Formula II below:
- wherein R11 and R12 are independently selected from the group consisting of heteroalkyl, hydroxyl, hydrogen, halogen, and substituted alkylaryl.
A method of potentiating a cancer cell for treatment with ionizing radiation or chemotherapeutics comprising contacting the cancer cell with an effective amount of a compound according to Formula I:
- wherein R4, R6, R7, and R9 are independently selected from alkyl, and hydrogen;
- X, Y, and Z are independently selected from the group consisting of O and NR14, wherein R13 and R14 are independently selected from the group consisting of alkyl, heteroalkyl, aryl, heteroaryl, ester, acyl, sulfonyl, heterocyclyl, amido, thioamido, acetyl, hydroxyl, amino, hydrogen, halogen, and cyano;
- R3 and R10 are independently selected from the group consisting of hydrogen, alkyl, and oxo;
- R5 and R8 are independently selected from the group consisting of substituted or unsubstituted phenyl;
- and
- R1 and R2 are independently selected from the group consisting of substituted or unsubstituted phenyl of Formula II below:
- wherein R11 and R12 are independently selected from the group consisting of heteroalkyl, hydroxyl, hydrogen, halogen, and substituted alkylaryl.
A compound selected from the following:
Dependencies are inferred from the claim text.