Preparation of phenylamide compounds as potassium ion channel modulators for therapeutic applications.

Abstract

The invention relates to compds. of general formula I (wherein Ar1 and Ar2 = aryl or heteroaryl; a and b = 0 to 5; R1 and R2 independently = alkyl, halogen, haloalkyl, etc.; W = O, S, S(O), etc.; Y and Z (the same or different) = CO, SO2, CONH, etc.; V = CH2CONH2, CH2CONH-alkyl, CH2CONH-aryl, etc.) and pharmacol. acceptable salts and pro-drugs thereof. Compds. of formula I may be used for the prophylaxis or treatment of diseases in which potassium ion channels KCNQ2, KCNQ3 or KCNQ2/3 are involved. Exemplary methods for synthesizing compds. of the invention were described, e.g., II was prepd. by a multi-step synthesis starting with 3-nitrophenyl acetic acid and culminating in the reaction of 2-(3-aminophenyl)-N-(2-hydroxyethyl)acetamide with 2,4,6-trichloro-1-bromobenzene to give II. Results show that example compds. demonstrate excellent enhancement of the KCNQ2/KCNQ3 potassium channel current, e.g., II showed a mean % enhancement of 168.2. [on SciFinder(R)]