Author/Authors :
Vivekananda M. Vrudhula، نويسنده , , Bireshwar Dasgupta، نويسنده , , Christopher G. Boissard، نويسنده , , Valentin K. Gribkoff، نويسنده , , Kenneth S. Santone، نويسنده , , Richard A. Dalterio، نويسنده , , Nicholas J. Lodge، نويسنده , , John E. Starrett Jr.، نويسنده ,
Abstract :
Quinolinone 1 is a potent maxi-K potassium channel opener. In an effort to design analogs of 1 with a better inhibitory profile toward the CYP2C9 isozyme, the two acidic sites were chemically modified independently to generate a number of analogs. These analogs were evaluated as maxi-K channel openers in vitro using Xenopus laevis oocytes expressing cloned hSlo maxi-K channels. Compounds 15, 17, and 19 showed potent activity as maxi-K channel openers and were further evaluated for inhibition of the activity of the CYP2C9 isozyme. Compounds 17 and 19 showed diminished inhibitory potency against 2C9 and also against a panel of other more common CYP isozymes.
