Triazole compounds that modulate HSP90 activity

摘要

The present invention relates to substituted triazole compounds and compositions comprising substituted triazole compounds. The invention further relates to methods of inhibiting the activity of Hsp90 in a subject in need thereof and methods for preventing or treating hyperproliferative disorders, such as cancer, in a subject in need thereof comprising administering to the subject a substituted triazole compound of the invention, or a composition comprising such a compound.

主权项

1. A compound represented by the following structural formula: or a tautomer, pharmaceutically acceptable salt, solvate, clathrate or a prodrug thereof, wherein: X′ is —O—O— or —S—S—; R′2 and R′3 are, independently, —OH, —SH, or —NHR7; R′5 is an optionally substituted heteroaryl or an optionally substituted aryl; R′6 is —H, an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, cyano, halo, nitro, an optionally substituted cycloalkyl, haloalkyl, an optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aralkyl, an optionally substituted heteroaralkyl, —OR7, —SR7, —NR10R11, —OC(O)NR10R11, —SC(O)NR10R11, —NR7C(O)NR10R11, —OC(O)R7, —SC(O)R7, —NR7C(O)R7, —OC(O)OR7, —SC(O)OR7, —NR7C(O)OR7, —OCH2C(O) R7, —SCH2C(O) R7, —NR7CH2C(O) R7, —OCH2C(O)OR7, —SCH2C(O)OR7, —NR7CH2C(O)OR7, —OcH2C(O)NR10R11, —SCH2C(O)NR10R11, —NR7CH2C(O)NR10R11, —OS(O)pR7, —SS(O)pR7, —NR7S(O)pR7, —OS(O)pNR10R11, —SS(O)pNR10R11, —NR7S(O)pNR10R11, —OS(O)pOR7, —SS(O)pOR7, —NR7S(O)pOR7, —OC(S)R7, —SC(S)R7, —NR7C(S)R7, —OC(S)OR7, —SC(S)OR7, —NR7C(S)OR7, —OC(S)NR10R11, —SC(S)NR10R11, —NR7C(S)NR10R11, —OC(NR8)R7, —SC(NR8)R7, —NR7C(NR8)R7, —OC(NR8)OR7, —SC(NR8)OR7, —NR7C(NR8)OR7, —OC(NR8)NR10R11, —SC(NR8)NR10R11, —NR7C(NR8)NR10R11, —C(O)R7, —C(O)OR7, —C(O)NR10R11, —C(O)SR7, —C(S)R7, —C(S)OR7, —C(S)NR10R11, —C(S)SR7, —C(NR8)OR7, —C(NR8)R7, —C(NR8)NR10R11, —C(NR8)SR7, —S(O)pOR7, —S(O)pNR10R11, or —S(O)pR7; R7 and R8, for each occurrence, is independently, —H, an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aralkyl, or an optionally substituted heteraralkyl; R10 and R11, for each occurrence, is independently —H, an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aralkyl, or an optionally substituted heteraralkyl; or R10 and R11, taken together with the nitrogen to which they are attached, form an optionally substituted heterocyclyl or an optionally substituted heteroaryl; p, for each occurrence, is independently 1 or 2.