Potent, Selective Pyrrolopyrimidine PDE11A4 Inhibitors with Improved Pharmaceutical Properties

ACS Medicinal Chemistry Letters 2026 Open access

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Authors: Shams ul Mahmood, Rama Krishna Boddu, Jeremy Eberhard, Charles S. Hoffman, John Gordon, Dennis J. Colussi, Wayne Childers, Elvis Amurrio, Marie Danaher, Michy P. Kelly, David P. Rotella
DOI: 10.1021/acsmedchemlett.5c00756
Cited by: 0
References: 10

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.

Fields of Study & Subjects

Phosphodiesterase function and regulation Adenosine and Purinergic Signaling Enzyme function and inhibition

Publication details

Journal / source
ACS Medicinal Chemistry Letters
Volume
17
Issue
2
Pages
547–553
Publication date
30 January 2026
Language
EN