| 摘要 |
PURPOSE: It is an object of the present invention to provide compounds which are useful for the treatment of diseases in mammals, including humans, and especially for the management of diseases which can be treated by inhibiting cell membrane potassium channels, such as the potassium channels responsible for cardiac I_kur potassium current, or the potassium channels responsible for Tlymphocyte I_kn potassium current, and potassium channels containing one of Kv1.5 or Kv1.3 a-subunit gene products. CONSTITUTION: Compounds of general formula (I) wherein R¬1 is H, alkyl or is selected from the group consisting of an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted heterocyclyl and an optionally substituted carbonyl; R¬2 is selected from the group consisting of alkyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted heterocyclyl and an optionally substituted carbonyl; R¬3 is hydrogen or methyl; R¬4 is hydrogen or methyl; X¬1 is C=O, C=S, or SO2; X¬2 is C=O or SO2; Y¬1 is O, (CH2)p, CH2O, HC=CH or NH; wherein p is 0, 1 or 2; Y¬2 is O, (CH2)q, HC=CH or NH; wherein q is 0 or 1; Z is H, OR¬5 or NR¬6R¬7; wherein R¬5 is H, (CH2)m-R¬8; or C(O)-(CH2)m-R¬8; m = 1 to 5; R¬8 is N(R¬9)2, N(R¬9)3L or CO2R¬9; wherein each R¬9 is independently selected from H or alkyl; and L is a counter ion; R¬6 is H or alkyl; R¬7 is H, alkyl or CO2R¬10; wherein R¬10 is alkyl; or pharmaceutically acceptable salts or prod rugs thereof are useful as potassium channel inhibitors and useful for the treatment of cardiac arrhythmias and cell proliferative disorders.
|
