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US 2019/0375731 A1Published application
Prodigiosin Analogs And Methods Of Use
AssigneeInstitute for Cancer Research d/b/a The Research Institute of Fox Chase Cancer Center
InventorsWafik S. El-Deiry, Xiaobing Tian
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Abstract
Prodigiosin analogs which reactivate the p53 pathway are provided, as well as compositions of these compounds, and methods for reactivation of the p53 pathway using these compounds are provided. The prodigiosin analogs may be used to treat cancer in which p53 mutation plays a role, including prostate cancer, breast cancer, kidney cancer, ovarian cancer, lymphoma, leukemia, and glioblastoma, among others.
Claims20
A compound of Formula XIV:
- wherein:
- R1 and R2 are, independently, selected from the group consisting of H, OH, halogen, —C1-6alkyl, —C1-6fluoroalkyl, —CN, —NO2, —OR7, —SR7, —S(═O)R7, —S(═O)2R7, —NHS(═O)2R7, —C(═O)R7, —OC(═O)R7, —CO2R7, —OCO2R7, —CH(R7)2, —N(R7)2, —C(═O)N(R7)2, —NHC(═O)NHR7, —NHC(═O)R7, —NHC(═O)OR7, —C(OH)(R7)2, and —C(NH2)(R7)2;
- each R7 is, independently, H, halogen, or C1-C6alkyl, wherein the alkyl group is optionally substituted by 1, 2, 3, 4, or 5 substituents independently selected from halogen, OH, CN, and NO2;
- R3 is an optionally substituted aryl or an optionally substituted heteroaryl;
- R4, R5, and R6 are, independently, OH, —C1-10alkyl, —OC1-10alkyl, or —SC1-10alkyl, wherein each alkyl group is, independently, optionally substituted by 1, 2, 3, 4, or 5 substituents independently selected from halogen, OH, CN, and NO2;
- and
- n is an integer from 0 to 5;
- or an isomer, tautomer, or solvate thereof, or a pharmaceutically acceptable salt thereof;
- provided that:
- if n is 0, then R3 is not an optionally substituted pyrrolyl;
- and
- if n is 2, then the compound is not
9 more elements
A method of preparing a compound of Formula XIV:
- wherein:
- R1 and R2 are, independently, selected from the group consisting of H, OH, halogen, —C1-6alkyl, —C1-6fluoroalkyl, —CN, —NO2, —OR7, —SR7, —S(═O)R7, —S(═O)2R7, —NHS(═O)2R7, —C(═O)R7, —OC(═O)R7, —CO2R7, —OCO2R7, —CH(R7)2, —N(R7)2, —C(═O)N(R7)2, —NHC(═O)NHR7, —NHC(═O)R7, —NHC(═O)OR7, —C(OH)(R7)2, and —C(NH2)(R7)2;
- each R7 is, independently, H, halogen, or C1-C6alkyl, wherein the alkyl group is optionally substituted by 1, 2, 3, 4, or 5 substituents independently selected from halogen, OH, CN, and NO2;
- R3 is an optionally substituted aryl or an optionally substituted heteroaryl;
- R4, R5, and R6 are, independently, —OH, —C1-10alkyl, —OC1-10alkyl, or —SC1-10alkyl, wherein each alkyl group is, independently, optionally substituted by 1, 2, 3, 4, or 5 substituents independently selected from halogen, OH, CN, and NO2;
- and
- n is an integer from 0 to 5;
- wherein the method comprises:
- admixing a solvent, an acid, a compound of Formula XII
- and a compound of Formula XIII
- at a temperature sufficient to result in the formation of the compound of Formula XIV;
- the acid is selected from the group consisting of hydrochloric acid, hydrobromic acid, hydrofluoric acid, acetic acid, phosphoric acid, toluenesulfonic acid, sulfuric acid, and nitric acid;
- and
- the temperature is about from about 0° C. to about 100° C.
11 more elements
Dependencies are inferred from the claim text.