SYNTHESIS OF DELTA 12-PGJ3 AND RELATED COMPOUNDS

摘要

In one aspect, the present invention provides novel derivatives of Δ12-PGJ3 and modular synthetic pathways to obtaining Δ12-PGJ3 and derivatives thereof. In some aspects, the present derivatives of Δ12-PGJ3 are useful as chemotherapeutic agents. The present disclosure also describes compositions of these derivatives as well as methods of use of the derivatives thereof.

主权项

1. A compound of the formula: wherein: Y1 is O, NR1, or N—OR1; wherein:
R1 is hydrogen, alkyl(C≦6), or substituted alkyl(C≦6); X1 is hydrogen, alkyl(C≦8), substituted alkyl(C≦8),or taken together with X2 as defined below;
wherein:
A1 is alkanediyl(C≦8), alkenediyl(C≦8), alkynediyl(C≦8), arenediyl(C≦12), heteroarenediyl(C≦12), or a substituted version of any of these groups;n is 0, 1, 2, 3, 4, 5, or 6;X3 is hydrogen, hydroxy, amino, cyano, or; alkyl(C≦12), alkenyl(C≦12), alkynyl(C≦12), aryl(C≦12), heteroaryl(C≦12), heterocycloalkyl(C≦12), alkoxy(C≦12), alkenyloxy(C≦12), alkynyloxy(C≦12), aryloxy(C≦12), heteroaryloxy(C≦12), heterocycloalkyloxy(C≦12), acyloxy(C≦12), alkylamino(C≦12), dialkylamino(C≦12), alkenylamino(C≦12), alkynylamino(C≦12), arylamino(C≦12), heteroarylamino(C≦12), heterocycloalkylamino(C≦12), amido(C≦12), or a substituted version of any of these groups; or —C(O)NR2R3, —C(O)R2; or —Y2—R4;
wherein:
R2 and R3 are each independently hydrogen, hydroxy, alkyl(C≦8), aryl(C≦8), alkoxy(C≦8), alkylsulfonyl(C≦8), arylsulfonyl(C≦8), or a substituted version of any of the last five groups; or R2 is -alkoxydiyl(C≦6)-S(O)2-aryl(C≦12) or a substituted version of this group; Y2 is alkanediyl(C≦12), substituted alkanediyl(C≦12); alkoxydiyl(C≦12), or substituted alkoxydiyl(C≦12); and R4 is hydrogen, —C(O)NR2R3, or —C(O)R2; wherein R2 and R3 are as defined above and X2 isor taken together with X1 as defined below;
wherein:
A2 is alkanediyl(C≦8), alkenediyl(C≦8), alkynediyl(C≦8) or a substituted version of any of these groups; or —CH2CH(OR4)—;wherein:
R4 is alkyl(C≦12); alkenyl(C≦12), alkynyl(C≦12), aryl(C≦12), heteroaryl(C≦12), acyl(C≦12), or a substituted version of any of these groups;X4 is hydrogen, hydroxy, oralkyl(C≦12), alkenyl(C≦12), alkynyl(C≦12), aryl(C≦12), heteroaryl(C≦12), heterocycloalkyl(C≦12), aryloxy(C≦12), heteroaryloxy(C≦12), heterocycloalkoxy(C≦12), arylthio(C≦12), heteroarylthio(C≦12), heterocycloalkylthio(C≦12), arylsulfinyl(C≦12), heteroarylsulfinyl(C≦12), heterocycloalkylsulfinyl(C≦12), arylsulfonyl(C≦12), heteroarylsulfonyl(C≦12), heterocycloalkylsulfonyl(C≦12), or a substituted version of any of these groups; ando is 1, 2, 3, 4, 5, or 6; wherein:
X1 and X2 are taken together as shown in formula (II): wherein:
Y1 is O, NH, or N—OR1;wherein:
R1 is hydrogen, alkyl(C≦6), or substituted alkyl(C≦6);A1 is alkanediyl(C≦8), alkenediyl(C≦8), alkynediyl(C≦8), arenediyl(C≦12), heteroarenediyl(C≦12), or a substituted version of any of these groups;z is 1, 2, 3, 4, 5, or 6;X5 is CR4R5, O, NH, NR6, or S;wherein:
R4, R5, and R6 are each independently H, alkyl(C≦8), aryl(C≦8), aralkyl(C≦8); or a substituted version of any of the last three groups; andX6 is alkyl(C≦12); alkenyl(C≦12), alkynyl(C≦12), aryl(C≦12), heteroaryl(C≦12) or a substituted version of any of these groups; provided that the compound does not have the formula: or a pharmaceutically acceptable salt thereof.