发明申请
US20120065270A1 POTASSIUM ION CHANNEL MODULATORS AND USES THEREOF 失效
钾离子通道调节剂及其用途

POTASSIUM ION CHANNEL MODULATORS AND USES THEREOF
摘要:
Compounds of formula (I) and pharmacologically acceptable salts and pro-drugs wherein: Ar1 and Ar2=aryl or heteroaryl; a=0 to 5; R1=alkyl, halogen, haloalkyl, alkoxy, alkoxycarbonyl, carboxyl, hydroxyl, amino, monalkylamino, dialkylamino, nitro, acylamino, alkoxycarbonylamino, alkylsulphonyl, alkylsulphonylamino and cyano and, where a is >1, each R1 is the same or different; b=0 to 5; R2=alkyl, halogen, haloalkyl, alkoxy, alkoxycarbonyl, carboxyl, hydroxyl, amino, monalkylamino, dialkylamino, nitro, acylamino, alkoxycarbonylamino, alkylsulphonyl, alkylsulphonylamino and cyano and where b is >1, each R2 is the same or different; V=(CR3aR3b)pSO2N(R3b)X and (CR3aR3b)pN(R3b)SO2(X); W=NR4a, O, S, S═O, SO2 and C(R4aR4b)2; X=hydroxyalkyl, alkoxyalkyl, haloalkoxyalkyl, aryloxyalkyl, polyalkylene glycol residues, aminoalkyl, monoalkylaminoalkyl, dialkylaminoalkyl and alkyl groups substituted with ≧1 NR8R9 groups wherein R8 and R9+nitrogen atom form a saturated or partially unsaturated heterocyclic group which is optionally further substituted by ≧1 substituents selected from alkyl, halogen, haloalkyl, alkoxy, alkoxycarbonyl, carboxyl, nitro, amino, monoalkylamino, dialkylamino and hydroxyl; Y and Z each ═(CR5aR5b)n1, C═O, SO2, C(═O)NR5a, C(═O)NR5aSO2 or C═O(R5aR5b)n2; R3a, R3b, R4a, R4b, R5a and R5b each=hydrogen, alkyl, cycloalkyl, aryl or heteroaryl; n1 and n2 each =0 to 2; and p=0 to 2; are excellent selective modulators of potassium ion flux through KCNQ2, KCNQ3 and/or KCNQ2/3 channels, making them of use in treating and preventing a number of conditions including pain and lower urinary tract disorders.
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