2020 - Addressing hERG activity while maintaining favorable potency, selectivity and pharmacokinetic properties of PPARδ modulators

icon pap   Port-a Patch Publication in Bioorganic & Medicinal Chemistry Letters (2020)

Authors:
Lagu B., Senaiar R.S., Kluge A.F., Mallesh B., Ramakrishna M., Bhat R., Patane M.A.

Journal:
Bioorganic & Medicinal Chemistry Letters (2020) 30(4): Article 126928


Abstract:

One of the most commonly used strategies to reduce hERG (human ether-a-go-go) activity in the drug candidates is introduction of a carboxylic acid group. During the optimization of PPARδ modulators, some of the compounds containing a carboxylic acid were found to inhibit the hERG channel in a patch clamp assay. By modifying the basicity of the imidazole core, potent and selective PPARδ modulators that do not inhibit hERG channel were identified. Some of the modulators have excellent pharmacokinetic profiles in mice.


Download here

Back to Overview

We use cookies on our website. Some of them are essential for the operation of the site, while others help us to improve this site and the user experience (tracking cookies).

You can decide for yourself whether you want to allow cookies or not. Please note that if you reject them, you may not be able to use all the functionalities of the site.