Triazole modified coumarin and biphenyl amide-based hsp90 inhibitors
AssigneeUniversity of Kansas
InventorsJinbo ZHAO, Huiping ZHAO, Brian S.J. BLAGG
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Abstract
Provided herein are compounds of the formulas: which are 90-kDa heat shock protein inhibitors. Pharmaceutical compositions of the compounds are also provided. In some aspects, these compounds may be used for the treatment of diseases, including cancer, e.g., cancers of the breast, the prostate, and the head & neck.
Claims86
A compound of the formula:
- wherein:
- R1 is alkyl(C≦12), cycloalkyl(C≦12), alkenyl(C≦12), cycloalkenyl(C≦12), alkynyl(C≦12), aryl(C≦12), aralkyl(C≦12), heteroaryl(C≦12), heteroaralkyl(C≦12), -alkanediyl(C≦8)-cycloalkyl(C≦12), -alkanediyl(C≦8)-cycloalkenyl(C≦12), or a substituted version of any of these groups;
- R2 is hydrogen, hydroxy, alkyl(C≦12), substituted alkyl(C≦12), cycloalkyl(C≦12), substituted cycloalkyl(C≦12), alkoxy(C≦12), substituted alkoxy(C≦12), cycloalkoxy(C≦12), or substituted cycloalkoxy(C≦12);
- R3 is hydrogen, alkyl(C≦12), cycloalkyl(C≦12), substituted alkyl(C≦12), or substituted cycloalkyl(C≦12);
- and
- X1 is heterocycloalkyl(C≦12) or substituted heterocycloalkyl(C≦12);
- or
- a compound of the formula:
- wherein:
- R4 is alkyl(C≦12), cycloalkyl(C≦12), alkenyl(C≦12), cycloalkenyl(C≦12), alkynyl(C≦12), aryl(C≦12), aralkyl(C≦12), heteroaryl(C≦12), heteroaralkyl(C≦12), -alkanediyl(C≦8)-cycloalkyl(C≦12), -alkanediyl(C≦8)-cycloalkenyl(C≦12), or a substituted version of any of these groups;
- R5 and R6 are each independently:
- amino, cyano, halo, hydroxy, nitro, hydroxysulfonyl, or sulfonamide;
- or
- alkyl(C≦12), cycloalkyl(C≦12), alkenyl(C≦12), alkynyl(C≦12), aryl(C≦12), aralkyl(C≦12), heteroaryl(C≦12), alkoxy(C≦12), acyl(C≦12), amido(C≦12), alkylamino(C≦12), dialkylamino(C≦12), alkylsulfonyl(C≦12), or a substituted version of any of these groups;
- n1 and n2 are each independently 0, 1, 2, 3, or 4;
- and
- X2 is heterocycloalkyl(C≦12) or substituted heterocycloalkyl(C≦12);
- or a pharmaceutically acceptable salt thereof.
A compound comprising a structure of Formula 1, derivative thereof, prodrug thereof, salt thereof, or stereoisomer thereof, or having any chirality at any chiral center, or tautomer, polymorph, solvate, or combination thereof:
- wherein R is any substituent.
A compound comprising a structure of Formula 2, derivative thereof, prodrug thereof, salt thereof, or stereoisomer thereof, or having any chirality at any chiral center, or tautomer, polymorph, solvate, or combination thereof:
- wherein R is any substituent.
A compound comprising a structure of Formula 3 or 4, derivative thereof, prodrug thereof, salt thereof, or stereoisomer thereof, or having any chirality at any chiral center, or tautomer, polymorph, solvate, or combination thereof:
- wherein the end ring can have an R substituent as any substituent, and n independently is any integer.
Dependencies are inferred from the claim text.