Potent, Selective Pyrrolopyrimidine PDE11A4 Inhibitors with Improved Pharmaceutical Properties
Shams ul Mahmood, Rama Krishna Boddu, Jeremy Eberhard, Charles S. Hoffman, John Gordon, Dennis Colussi, Wayne Childers, Elvis Amurrio, Marie Danaher, Michy P. Kelly, David P. Rotella
TL;DR
Researchers developed a new PDE11A4 inhibitor with better solubility and effectiveness for potential therapeutic use.
Contribution
A novel pyrrolopyrimidine PDE11A4 inhibitor with improved pharmaceutical properties and potency was developed.
Findings
The compound shows potent and selective inhibition of PDE11A4.
It has improved aqueous solubility compared to previous compounds.
The inhibitor demonstrates promising activity in cell-based models.
Abstract
Previous work demonstrated target engagement with an orally bioavailable, potent, selective PDE11A4 inhibitor in the mouse hypothalamus. This compound was limited by low aqueous solubility, stimulating the need for alternative leads with improved pharmaceutical properties to carry out efficacy studies. This paper outlines optimization of a pyrrolopyrimidine hit leading to a potent, selective PDE11A4 inhibitor with improved pharmaceutical properties and promising activity in cell-based models of enzyme activity.
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Taxonomy
TopicsPhosphodiesterase function and regulation · Pharmaceutical Quality and Counterfeiting · Biochemical and Molecular Research