[发明专利]调节HSP90活性的三唑化合物

摘要

本发明涉及调节HSP90活性的取代的三唑化合物及包含被取代三唑化合物的组合物。本发明进一步涉及抑制有需要个体内Hsp90活性的药物组合物，及用于预防或治疗有需要个体的过度增生性疾病（例如癌症）的药物组合物，其包括将本发明的被取代三唑化合物，或包含此类化合物的组合物给药予该个体。

主权项

1.一种由下列结构式所代表的化合物：或其互变异构体、可药用盐类或溶剂合物，其中：R₁及R₃独立地为-OH、-SH、-NR₇H、-OR₂₆、-SR₂₆、-NHR₂₆、-O(CH₂)_mOH、-O(CH₂)_mSH、-O(CH₂)_mNR₇H、-S(CH₂)_mOH、-S(CH₂)_mSH、-S(CH₂)_mNR₇H、-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、-S(O)_pOR₇、-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、-OP(O)(OR₇)₂、或-SP(O)(OR₇)₂；R₂为取代的苯基，其中该苯基经下列取代：i)一个选自硝基、氰基、卤烷氧基、任选取代的烯基、任选取代的炔基、任选取代的环烷基、任选取代的环烯基、任选取代的杂环基、任选取代的芳基、任选取代的杂芳基、任选取代的芳烷基、任选取代的杂芳烷基、羟烷基、烷氧烷基、胍基、-NR₁₀R₁₁、-C(O)R₇、-C(O)OR₂₀、-OC(O)R₇、-C(O)NR₁₀R₁₁、-NR₈C(O)R₇、-SR₇、-S(O)_pR₇、-OS(O)_pR₇、-S(O)_pOR₇、-NR₈S(O)_pR₇、或-S(O)_pNR₁₀R₁₁、-S(O)_pOR₇、-OP(O)(OR₇)₂或-SP(O)(OR₇)₂的取代基，或ii)二至五个选自任选取代的烷基、任选取代的烯基、任选取代的炔基、任选取代的环烷基、任选取代的环烯基、任选取代的杂环基、任选取代的芳基、任选取代的杂芳基、任选取代的芳烷基或任选取代的杂芳烷基、羟烷基、烷氧烷基、-Br、-I、氰基、硝基、胍基、卤烷基、杂烷基、-NR₁₀R₁₁、-C(O)R₇、-C(O)OR₇、-OC(O)R₇、-C(O)NR₁₀R₁₁、-NR₈C(O)R₇、-SR₇、-S(O)_pR₇、-OS(O)_pR₇、-S(O)_pOR₇、-NR₈S(O)_pR₇、或-S(O)_pNR₁₀R₁₁、-OP(O)(OR₇)₂、-SP(O)(OR₇)₂或-S(O)_pOR₇的取代基；且R₇与R₈每次出现时，各自独立地为-H、任选取代的烷基、任选取代的烯基、任选取代的炔基、任选取代的环烷基、任选取代的环烯基、任选取代的杂环基、任选取代的芳基、任选取代的杂芳基、任选取代的芳烷基或任选取代的杂芳烷基；R₁₀与R₁₁每次出现时，各自独立地为-H、任选取代的烷基、任选取代的烯基、任选取代的炔基、任选取代的环烷基、任选取代的环烯基、任选取代的杂环基、任选取代的芳基、任选取代的杂芳基、任选取代的芳烷基或任选取代的杂芳烷基；或者R₁₀与R₁₁一起与其所连接的氮形成任选取代的杂环基或任选取代的杂芳基；R₂₆为C1-C6烷基；p每次出现时，各自独立地为0、1或2；且m每次出现时，各自独立地为1、2、3或4；R₂₀每次出现时，各自独立地为任选取代的烷基、任选取代的烯基、任选取代的炔基、任选取代的环烷基、任选取代的环烯基、任选取代的杂环基、任选取代的芳基、任选取代的杂芳基、任选取代的芳烷基或任选取代的杂芳烷基;R₂₅为任选取代的烷基、任选取代的烯基、任选取代的炔基、任选取代的环烷基、任选取代的环烯基、任选取代的杂环基、任选取代的芳基、任选取代的杂芳基、任选取代的芳烷基、或任选取代的杂芳烷基、卤基、氰基、硝基、胍基、卤烷基、杂烷基、烷氧基、卤烷氧基、-NR₁₀R₁₁、-OR₇、-C(O)R₇、-C(O)OR₇、-C(S)R₇、-C(O)SR₇、-C(S)SR₇、-C(S)OR₇、-C(S)NR₁₀R₁₁、-C(NR₈)OR₇、-C(NR₈)R₇、-C(NR₈)NR₁₀R₁₁、-C(NR₈)SR₇、-OC(O)R₇、-OC(O)OR₇、-OC(S)OR₇、-OC(NR₈)OR₇、-SC(O)R₇、-SC(O)OR₇、-SC(NR₈)OR₇、-OC(S)R₇、-SC(S)R₇、-SC(S)OR₇、-OC(O)NR₁₀R₁₁、-OC(S)NR₁₀R₁₁、-OC(NR₈)NR₁₀R₁₁、-SC(O)NR₁₀R₁₁、-SC(NR₈)NR₁₀R₁₁、-SC(S)NR₁₀R₁₁、-OC(NR₈)R₇、-SC(NR₈)R₇、-C(O)NR₁₀R₁₁、-NR₈C(O)R₇、-NR₇C(S)R₇、-NR₇C(S)OR₇、-NR₇C(NR₈)R₇、-NR₇C(O)OR₇、-NR₇C(NR₈)OR₇、-NR₇C(O)NR₁₀R₁₁、-NR₇C(S)NR₁₀R₁₁、-NR₇C(NR₈)NR₁₀R₁₁、-SR₇、-S(O)_pR₇、-OS(O)_pR₇、-OS(O)_pOR₇、-OS(O)_pNR₁₀R₁₁、-S(O)_pOR₇、-NR₈S(O)_pR₇、-NR₇S(O)_pNR₁₀R₁₁、-NR₇S(O)_pOR₇、-S(O)_pNR₁₀R₁₁、-SS(O)_pR₇、-SS(O)_pOR₇、-SS(O)_pNR₁₀R₁₁、-OP(O)(OR₇)₂、或-SP(O)(OR₇)₂；R₆在每次出现时，各自独立地为任选取代的烷基、任选取代的烯基、任选取代的炔基、任选取代的环烷基、任选取代的环烯基、任选取代的杂环基、任选取代的芳基、任选取代的杂芳基、任选取代的芳烷基、或任选取代的杂芳烷基、卤基、氰基、硝基、胍基、卤烷基、杂烷基、烷氧基、卤烷氧基、-NR₁₀R₁₁、-OR₇、-C(O)R₇、-C(O)OR₇、-C(S)R₇、-C(O)SR₇、-C(S)SR₇、-C(S)OR₇、-C(S)NR₁₀R₁₁、-C(NR₈)OR₇、-C(NR₈)R₇、-C(NR₈)NR₁₀R₁₁、-C(NR₈)SR₇、-OC(O)R₇、-OC(O)OR₇、-OC(S)OR₇、-OC(NR₈)OR₇、-SC(O)R₇、-SC(O)OR₇、-SC(NR₈)OR₇、-OC(S)R₇、-SC(S)R₇、-SC(S)OR₇、-OC(O)NR₁₀R₁₁、-OC(S)NR₁₀R₁₁、-OC(NR₈)NR₁₀R₁₁、-SC(O)NR₁₀R₁₁、-SC(NR₈)NR₁₀R₁₁、-SC(S)NR₁₀R₁₁、-OC(NR₈)R₇、-SC(NR₈)R₇、-C(O)NR₁₀R₁₁、-NR₈C(O)R₇、-NR₇C(S)R₇、-NR₇C(S)OR₇、-NR₇C(NR₈)R₇、-NR₇C(O)OR₇、-NR₇C(NR₈)OR₇、-NR₇C(O)NR₁₀R₁₁、-NR₇C(S)NR₁₀R₁₁、-NR₇C(NR₈)NR₁₀R₁₁、-SR₇、-S(O)_pR₇、-OS(O)_pR₇、-OS(O)_pOR₇、-OS(O)_pNR₁₀R₁₁、-S(O)_pOR₇、-NR₈S(O)_pR₇、-NR₇S(O)_pNR₁₀R₁₁、-NR₇S(O)_pOR₇、-S(O)_pNR₁₀R₁₁、-SS(O)_pR₇、-SS(O)_pOR₇、-SS(O)_pNR₁₀R₁₁、-OP(O)(OR₇)₂、或-SP(O)(OR₇)₂；和r为1-3的整数。