523992-06-5Relevant academic research and scientific papers
BICYCLIC FUSED PYRAZOLE DERIVATIVES FOR THE TREATMENT OF RSV
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Page/Page column 89; 90, (2017/12/05)
Disclosed herein are compounds and compositions for treating or inhibiting RSV and related members of the pneumovirus and paramyxovirus families such as human metapneumovirus, mumps virus, human parainfluenzaviruses, and Nipah and hendra virus, and method
First in class, potent, and orally bioavailable NADPH oxidase isoform 4 (Nox4) inhibitors for the treatment of idiopathic pulmonary fibrosis
Laleu, Beno?t,Gaggini, Francesca,Orchard, Mike,Fioraso-Cartier, Laetitia,Cagnon, Laurène,Houngninou-Molango, Sophie,Gradia, Angelo,Duboux, Guillaume,Merlot, Cédric,Heitz, Freddy,Szyndralewiez, Cédric,Page, Patrick
experimental part, p. 7715 - 7730 (2010/12/30)
We describe the design, synthesis, and optimization of first-in-class series of inhibitors of NADPH oxidase isoform 4 (Nox4), an enzyme implicated in several pathologies, in particular idiopathic pulmonary fibrosis, a life-threatening and orphan disease. Initially, several moderately potent pyrazolopyridine dione derivatives were found during a high-throughput screening campaign. SAR investigation around the pyrazolopyridine dione core led to the discovery of several double-digit nanomolar inhibitors in cell free assays of reactive oxygen species (ROS) production, showing high potency on Nox4 and Nox1. The compounds have little affinity for Nox2 isoform and are selective for Nox4/1 isoforms. The specificity of these compounds was confirmed in an extensive in vitro pharmacological profile, as well as in a counterscreening assay for potential ROS scavenging. Concomitant benefits are good oral bioavailability and high plasma concentrations in vivo, allowing further clinical trials for the potential treatment of fibrotic diseases, cancers, and cardiovascular and metabolic diseases.
