DISCOVERY OF A NOVEL CLASS OF BK CHANNEL OPENERS - ENANTIOSPECIFIC SYNTHESIS AND BK CHANNEL OPENING ACTIVITY OF HYDRO-3-HYDROXY-6-(TRIFLUOROMETHYL)-2H-INDOL-2-ONE

3-Aryl-3-hydroxyindol-2-ones have been identified as a novel class of BK channel openers. Synthesis of both racemic and chiral 3-aryl-3-hydr oxyindolones is described along with their electrophysiological evalua tion as activators of the cloned BK channel mSlo expressed in Xenopus laevis oocytes. The preliminary SAR data indicate the importance of bo th an electron-withdrawing substituent on the oxindole nucleus and the phenolic hydroxyl for expression of BK channel opening properties. Mo reover, the dependence of BK channel opening activity on the absolute configuration of the chiral center in this pharmacophore has been demo nstrated. (C) 1997 Elsevier Science Ltd.