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Lead Optimization of Positive Allosteric KV7.2/3...
Journal article

Lead Optimization of Positive Allosteric KV7.2/3 Channel Modulators toward Improved Balance of Lipophilicity and Aqueous Solubility

Abstract

The voltage-gated potassium channel KV7.2/3 is gaining attention for its association with several medical indications. While recently reported, potent compounds aimed to fill the therapeutic gap left by market-withdrawn activators, key physicochemical parameters did not meet the requirements of potential drug candidates. Targeting the membrane-located channel requires subtly balancing lipophilicity, activity, and aqueous solubility. This …

Authors

Lemke J; Mengers N; Schmidt L; Schulig L; König S; Rosendahl P; Bartz F-M; Garscha U; Bednarski PJ; Link A

Journal

Journal of Medicinal Chemistry, Vol. 68, No. 8, pp. 8377–8399

Publisher

American Chemical Society (ACS)

Publication Date

April 24, 2025

DOI

10.1021/acs.jmedchem.4c03112

ISSN

0022-2623