2. Academic Validation
  3. Analogs of a potent maxi-K potassium channel opener with an improved inhibitory profile toward cytochrome P450 isozymes

Analogs of a potent maxi-K potassium channel opener with an improved inhibitory profile toward cytochrome P450 isozymes

  • Bioorg Med Chem Lett. 2005 Oct 1;15(19):4286-90. doi: 10.1016/j.bmcl.2005.06.056.
Vivekananda M Vrudhula 1,  Bireshwar Dasgupta,  Christopher G Boissard,  Valentin K Gribkoff,  Kenneth S Santone,  Richard A Dalterio,  Nicholas J Lodge,  John E Starrett Jr
Affiliations

Affiliation

  • 1 Bristol-Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, CT 06492, USA. [email protected]
PMID: 16061379 DOI: 10.1016/j.bmcl.2005.06.056
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.

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