TWO-CARBON LINKED ARTEMISININ-DERIVED TRIOXANE DIMERS

摘要

Two-carbon linked artemisinin-derived trioxane dimers and methods of their use for treating subjects infected with malaria or other parasitic infectious diseases including, but not limited to, toxoplasmic infection; subjects afflicted with psychiatric conditions associated with toxoplasmic infection; and subjects afflicted with cancer.

主权项

1. A compound of Formula (I):wherein:
X is selected from the group consisting of C(═O); C═NR1; C═NOR2; C═NNHR3; and CH—O—R4; R1 is selected from the group consisting of substituted or unsubstituted linear or branched alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloheteroalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl; R2 is selected from the group consisting of H, substituted or unsubstituted linear or branched alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, —P(═O)(OR5)(OR5), wherein each R5 is independently lower linear or branched alkyl, aryl or heteroaryl, and —C(═O)R6, wherein R6 is substituted or unsubstituted linear or branched alkyl, substituted or unsubstituted cycloalkyl, alkoxyl, aryloxyl, substituted or unsubstituted cycloheteroalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, and NR7R8, wherein R7 and R8 are each independently selected from the group consisting of H, substituted or unsubstituted linear or branched alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloheteroalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl; R3 is selected from the group consisting of substituted or unsubstituted linear or branched alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloheteroalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, and —(C═O)R9, wherein R9 is selected from the group consisting of substituted or unsubstituted linear or branched alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloheteroalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl; R4 is selected from the group consisting of H, substituted or unsubstituted linear or branched alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —P(═O)(OR5)(OR5), wherein each R5 is independently lower linear or branched alkyl, aryl or heteroaryl, and —C(═O)R10, wherein R10 is substituted or unsubstituted linear or branched alkyl, substituted or unsubstituted cycloalkyl, alkoxyl, aryloxyl, substituted or unsubstituted cycloheteroalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, and NR11R12, wherein R11 and R12 are each independently selected from the group consisting of H, substituted or unsubstituted linear or branched alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloheteroalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl; or an enantiomer, diastereomer, racemate or pharmaceutically acceptable salt, prodrug, or solvate thereof.