KCNQ Potassium Channels Modulators

Title Aminoalkyl Thiazole Derivatives as KCNQ Modulators K.M. Boy et al US Patent 6,933,308 (August 23, 2005) 

Invention Significance Although the symptom pattern and severity vary 

Preparation 2-amino-4-trifluoromethyl-thiazole-5-carboxylic acid ethyl ester 

Ethyl 2-chloro-4,4,4-trifluoroacetoacetate (230 mmol) dissolved in 250 ml ethyl alcohol was treated with thiourea (230 mmol), then refluxed 3 hours, and concentrated. The residue was dissolved in diethyl ether and washed with aqueous NaHC03 and brine. The solution was dried with MgS04, then recrystallized with EtOAc and hexanes, and the product isolated in 75% yield as white crystals. 

---

Fluoro-2-oxindole derivatives, (IV), prepared by Dworetzky (5) were effective modulators of KCNQ potassium channels and used in treating migraine and mechanistically related disease. 

---