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Updated: Aug 29, 2026

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Published on: May 9, 2025
Structure-activity relationships of N-acyl pyrroloquinolone PDE-5 inhibitors
James C Lanter1, Zhihua Sui, Mark J Macielag
1Drug Discovery, Johnson and Johnson Pharmaceutical Research and Development LLC, 1000 Route 202 S, P.O. Box 300, Raritan, New Jersey 08869, USA. jlanter@prdus.jnj.com
Abstract:
The discovery of the potent and selective PDE-5 inhibitory activity of a pyrroloquinolone scaffold prompted us to explore the SAR of its acyl derivatives. During the course of these studies, three structural series were found with K(i) values for PDE-5 in the subnanomolar range. Systematic modification of one of these leads produced a compound with excellent selectivity for PDE-5 over other phosphodiesterases and oral bioavailability of 15% in male rats. This compound also displayed in vivo efficacy in an anesthetized canine model of erection when dosed intravenously.
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