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Potent, Selective Pyrrolopyrimidine PDE11A4 Inhibitors with Improved Pharmaceutical Properties
Shams Ul Mahmood1, Rama Krishna Boddu1, Jeremy Eberhard2
1Department of Chemistry and Biochemistry, Sokol Institute of Pharmaceutical Life Sciences, Montclair State University, Montclair, New Jersey 07043, United States.
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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