作为治疗剂的异噁唑-3(2H)-酮类似物

摘要

本发明涉及式I或其药学上合适的盐，其中，R1和R2独立地是氢、氘、芳基、杂芳基、C1-C8烷基，任选被一个或多个独立地是R3的取代基取代；R3是芳基、杂芳基、氟、含有一个或多个氟的C1-C6烷基、含有一个或多个氘的C1-C6烷基、含有羟基的C1-C6烷基，所述芳基和杂芳基任选被下列取代：一个或多个卤素、氟代烷氧基、氟代烷基、磺酰基、一个或多个氘、C1-6烷基、C1-6烷氧基、氰基，或R3是任选被一个或多个下列基团取代的C1-6烷基：COOR4、OCOR4、CONR5R6、NR5COR6、OR4；其中，R4是任选被下列取代的C1-10烷基：一个或多个氟，氘、烷氧基、芳基羧酸酯基、烷基羧酸酯基；R5和R6独立地选自氢、烷基，或它们可以一起形成4-8元碳环；或R1和R2形成任选包含O或N并且任选被下列取代的3-10元碳环：任选被R3取代的C1-10烷基或芳基、杂芳基。

主权项

1.选自以下的化合物或其药学上合适的盐∶5-((2S,4S)-2-苄基哌啶-4-基)异噁唑-3(2H)-酮；5-((2R,4R)-2-苄基哌啶-4-基)异噁唑-3(2H)-酮；5-((2R,4S)-2-苄基哌啶-4-基)异噁唑-3(2H)-酮；5-((2S,4R)-2-苄基哌啶-4-基)异噁唑-3(2H)-酮；5-((2R,4S)-2-异丁基哌啶-4-基)异噁唑-3(2H)-酮；5-((2S,4R)-2-异丁基哌啶-4-基)异噁唑-3(2H)-酮；5-((2S,4S)-2-异丁基哌啶-4-基)异噁唑-3(2H)-酮；5-((2R,4S)-2-苯乙基哌啶-4-基)异噁唑-3(2H)-酮；5-((2S,4R)-2-苯乙基哌啶-4-基)异噁唑-3(2H)-酮；5-((2S,4S)-2-苯乙基哌啶-4-基)异噁唑-3(2H)-酮；5-((2S,4S)-2-(4-叔丁基苄基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2R,4S)-2-(4-叔丁基苄基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2S,4S)-2-新戊基哌啶-4-基)异噁唑-3(2H)-酮；5-((2R,4S)-2-新戊基哌啶-4-基)异噁唑-3(2H)-酮；5-((2R,4S)-2-甲基哌啶-4-基)异噁唑-3(2H)-酮；5-((2S,4R)-2-甲基哌啶-4-基)异噁唑-3(2H)-酮；5-((2S,4S)-2-甲基哌啶-4-基)异噁唑-3(2H)-酮；5-((2S,4S)-2-(2-甲基-2-苯丙基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2R,4S)-2-(2-甲基-2-苯丙基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2R,4S)-2-(环己基甲基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2R,4R)-2-(环己基甲基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2S,4S)-2-(环己基甲基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2R,4S)-2-(3,4-二氟苯基)哌啶-4-基)异噁唑-3(2H)-酮；5-(反式-2-(3,4-二氟苯基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2R,4S)-2-(4-氟苯基)哌啶-4-基)异噁唑-3(2H)-酮；5-(反式-2-(4-氟苯基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2R,4S)-2-(4-氯苯基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2S,4R)-2-(4-氯苯基)哌啶-4-基)异噁唑-3(2H)-酮；5-(反式-2-(4-氯苯基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2R,4S)-2-(3-(三氟甲基)苯基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2S,4R)-2-(3-(三氟甲基)苯基)哌啶-4-基)异噁唑-3(2H)-酮；5-(反式-2-(3-(三氟甲基)苯基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2R,4S)-2-(4-(三氟甲基)苯基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2S,4R)-2-(4-(三氟甲基)苯基)哌啶-4-基)异噁唑-3(2H)-酮；5-(反式-2-(4-(三氟甲基)苯基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2R,4S)-2-(3-叔丁基苯基)哌啶-4-基)异噁唑-3(2H)-酮；5-(反式-2-(4-叔丁基苯基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2R,4S)-2-(4-(甲基磺酰基)苯基)哌啶-4-基)异噁唑-3(2H)-酮；5-((反式-2-(4-(甲基磺酰基)苯基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2R,4S)-2-(6-(三氟甲基)吡啶-3-基)哌啶-4-基)异噁唑-3(2H)-酮；5-(反式-2-(6-(三氟甲基)吡啶-3-基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2R,4S)-2-(5-叔丁基噻吩-2-基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2S,4R)-2-(5-叔丁基噻吩-2-基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2R,4S)-2-(2,4-二氟苯基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2R,4S)-2-(4-氯-2-氟苯基)哌啶-4-基)异噁唑-3(2H)-酮；5-(反式-2-(4-氯-2-氟苯基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2R,4S)-2-(2-氯-4-氟苯基)哌啶-4-基)异噁唑-3(2H)-酮；5-(反式-2-(2-氯-4-氟苯基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2R,4S)-2-(4-氯-3-氟苯基)哌啶-4-基)异噁唑-3(2H)-酮；5-(反式-2-(4-氯-3-氟苯基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2R,4S)-2-(2,4-二氯苯基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2S,4R)-2-(2,4-二氯苯基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2S,4S)-2-(2,4-二氯苯基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2R,4R)-2-(2,4-二氯苯基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2R,4S)-2-(3,5-二氯苯基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2S,4R)-2-(3,5-二氯苯基)哌啶-4-基)异噁唑-3(2H)-酮；5-(反式-2-(3,5-二氯苯基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2R,4S)-2-(2-氟-4-(三氟甲氧基)苯基)哌啶-4-基)异噁唑-3(2H)-酮；5-(反式-2-(2-氟-4-(三氟甲氧基)苯基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2R,4S)-2-(3,4,5-三氟苯基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2S,4R)-2-(3,4,5-三氟苯基)哌啶-4-基)异噁唑-3(2H)-酮；5-(反式-2-(3,4,5-三氟苯基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2R,4S)-2-(2,4,5-三氟苯基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2S,4S)-2-(2,4,5-三氟苯基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2R,4S)-2-(4-氯-3,5-二氟苯基)哌啶-4-基)异噁唑-3(2H)-酮；5-(反式-2-(4-氯-3,5-二氟苯基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2R,4S)-2-(3-甲基-4-(三氟甲基)苯基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2S,4R)-2-(3-甲基-4-(三氟甲基)苯基)哌啶-4-基)异噁唑-3(2H)-酮；5-(反式-2-(3-甲基-4-(三氟甲基)苯基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2R,4S)-2-(3,5-二氟-4-(三氟甲基)苯基)哌啶-4-基)异噁唑-3(2H)-酮；5-(反式-2-(3,5-二氟-4-(三氟甲基)苯基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2R,4S)-2-(2-甲基-4-(三氟甲基)苯基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2R,4S)-2-(2-氟-4-(三氟甲基)苯基)哌啶-4-基)异噁唑-3(2H)-酮；5-(反式-2-(2-氟-4-(三氟甲基)苯基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2R,4S)-2-(3-氟-4-(三氟甲基)苯基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2S,4R)-2-(3-氟-4-(三氟甲基)苯基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2R,4S)-2-苯基哌啶-4-基)异噁唑-3(2H)-酮；5-((2S,4S)-2-苯基哌啶-4-基)异噁唑-3(2H)-酮；5-((2R,4S)-2-环己基哌啶-4-基)异噁唑-3(2H)-酮；5-((2S,4S)-2-环己基哌啶-4-基)异噁唑-3(2H)-酮；5-((2R,4S)-2-(2-甲基-2H-四唑-5-基)哌啶-4-基)异噁唑-3(2H)-酮；5-(反式-2-(2-甲基-2H-四唑-5-基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2R,4S)-2-(1-甲基-1H-四唑-5-基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2R,4S)-2-(环己基氧基甲基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2S,4R)-2-(环己基氧基甲基)哌啶-4-基)异噁唑-3(2H)-酮；5-(反式-2-(环己基氧基甲基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2R,4S)-2-(二氟甲基)哌啶-4-基)异噁唑-3(2H)-酮；5-(反式-2-(二氟甲基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2S,4S)-2-((4,4-二氟环己基)甲基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2R,4R)-2-((4,4-二氟环己基)甲基)哌啶-4-基)异噁唑-3(2H)-酮；5-(反式-2-((4,4-二氟环己基)甲基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2S,4S)-2-(4-氟苯乙基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2R,4R)-2-(4-氟苯乙基)哌啶-4-基)异噁唑-3(2H)-酮；5-(反式-2-(4-氟苯乙基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2S,4S)-2-(3,3-二甲基丁基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2R,4S)-2-(3,3-二甲基丁基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2R,4S)-2-(4-氟苄基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2S,4S)-2-(4-氟苄基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2R,4S)-2-(3-氟苄基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2S,4S)-2-(3-氟苄基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2R,4S)-2-(2-氟苄基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2S,4S)-2-(2-氟苄基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2R,4R)-2-(2-氟苄基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2R,4S)-2-(4-(三氟甲基)苄基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2S,4S)-2-(4-(三氟甲基)苄基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2R,4R)-2-(4-(三氟甲基)苄基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2R,4S)-2-(3-(三氟甲基)苄基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2S,4R)-2-(3-(三氟甲基)苄基)哌啶-4-基)异噁唑-3(2H)-酮；5-(反式-2-(3-(三氟甲基)苄基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2R,4S)-2-(2-(三氟甲基)苄基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2S,4R)-2-(2-(三氟甲基)苄基)哌啶-4-基)异噁唑-3(2H)-酮；5-(反式-2-(2-(三氟甲基)苄基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2R,4S)-2-(4-(三氟甲氧基)苄基)哌啶-4-基)异噁唑-3(2H)-酮；5-(反式-2-(4-(三氟甲氧基)苄基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2R,4S)-2-(4-氯苄基)哌啶-4-基)异噁唑-3(2H)-酮；5-(反式-2-(4-氯苄基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2R,4S)-2-(4-(甲基磺酰基)苄基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2S,4R)-2-(4-(甲基磺酰基)苄基)哌啶-4-基)异噁唑-3(2H)-酮；5-(反式-2-(4-(甲基磺酰基)苄基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2R,4S)-2-(3,4-二氟苄基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2S,4R)-2-(3,4-二氟苄基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2S,4S)-2-(3,4-二氟苄基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2R,4R)-2-(3,4-二氟苄基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2R,4S)-2-(2,5-二氟苄基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2S,4R)-2-(2,5-二氟苄基)哌啶-4-基)异噁唑-3(2H)-酮；5-(反式-2-(2,5-二氟苄基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2R,4S)-2-(2,6-二氟苄基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2S,4R)-2-(2,6-二氟苄基)哌啶-4-基)异噁唑-3(2H)-酮；5-(反式-2-(2,6-二氟苄基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2R,4S)-2-(3,5-二氟苄基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2S,4R)-2-(3,5-二氟苄基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2S,4S)-2-(3,5-二氟苄基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2R,4R)-2-(3,5-二氟苄基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2R,4S)-2-(2,4-二氟苄基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2S,4R)-2-(2,4-二氟苄基)哌啶-4-基)异噁唑-3(2H)-酮；5-(反式-2-(2,4-二氟苄基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2R,4S)-2-(3-氟-5-(三氟甲基)苄基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2S,4R)-2-(3-氟-5-(三氟甲基)苄基)哌啶-4-基)异噁唑-3(2H)-酮；5-(反式-2-(3-氟-5-(三氟甲基)苄基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2R,4S)-2-(3-氟-4-(三氟甲基)苄基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2S,4R)-2-(3-氟-4-(三氟甲基)苄基)哌啶-4-基)异噁唑-3(2H)-酮；5-(反式-2-(3-氟-4-(三氟甲基)苄基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2R,4S)-2-(3,4,5-三氟苄基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2S,4R)-2-(3,4,5-三氟苄基)哌啶-4-基)异噁唑-3(2H)-酮；5-(反式-2-(3,4,5-三氟苄基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2R,4S)-2-(3,5-二叔丁基苄基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2S,4R)-2-(3,5-二叔丁基苄基)哌啶-4-基)异噁唑-3(2H)-酮；5-(反式-2-(3,5-二叔丁基苄基)哌啶-4-基)异噁唑-3(2H)-酮；5-((2R,4S)-2-苄基-2,3,4,5,6-d5-哌啶-4-基)异噁唑-3(2H)-酮；5-((2S,4R)-2-苄基-2,3,4,5,6-d5-哌啶-4-基)异噁唑-3(2H)-酮；5-(反式-2-苄基-2,3,4,5,6-d5-哌啶-4-基)异噁唑-3(2H)-酮。