Potent, Selective Pyrrolopyrimidine PDE11A4 Inhibitors with Improved Pharmaceutical Properties
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.
Authors
- Dennis Colussi
- Jeremy Eberhard
- David P. Rotella (ORCID: https://orcid.org/0000-0002-8224-218X)
- Charles S. Hoffman (ORCID: https://orcid.org/0000-0001-8700-1863)
- Elvis Amurrio
- Rama Krishna Boddu
- Shams ul Mahmood
- Michy P. Kelly
- John Gordon
- Wayne Childers
- Marie Danaher
Institutions
- Boston College (US)
- University of Maryland, Baltimore (US)
- Montclair State University (US)
- Temple College (US)
- Ono Pharmaceutical (United States) (US)
- Institute on Aging (US)
- Drug Discovery Laboratory (Norway) (NO)
- Temple University (US)
Publication Details
- Journal
- ACS Medicinal Chemistry Letters
- Published
- 2026-01-30
- DOI
- https://doi.org/10.1021/acsmedchemlett.5c00756
- Primary Topic
- Phosphodiesterase function and regulation
- Type
- article
- Field-Weighted Citation Impact
- 0.00