25912-15-6Relevant academic research and scientific papers
HMOX1 inducers
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, (2020/09/18)
The present invention is related to compounds of structure (I) as heme oxygenase 1 (HMOX 1) inducers. The present invention is also related a method of controlling the activity or the amount, or both the activity and the amount, of heme-oxygenase 1 in a mammalian subject. The definitions of the variables are provided herein.
Lead Optimization of Benzoxazolone Carboxamides as Orally Bioavailable and CNS Penetrant Acid Ceramidase Inhibitors
Di Martino, Simona,Tardia, Piero,Cilibrasi, Vincenzo,Caputo, Samantha,Mazzonna, Marco,Russo, Debora,Penna, Ilaria,Realini, Natalia,Margaroli, Natasha,Migliore, Marco,Pizzirani, Daniela,Ottonello, Giuliana,Bertozzi, Sine Mandrup,Armirotti, Andrea,Nguyen, Duc,Sun, Ying,Bongarzone, Ernesto R.,Lansbury, Peter,Liu, Min,Skerlj, Renato,Scarpelli, Rita
, p. 3634 - 3664 (2020/04/30)
Sphingolipids (SphLs) are a diverse class of molecules that are regulated by a complex network of enzymatic pathways. A disturbance in these pathways leads to lipid accumulation and initiation of several SphL-related disorders. Acid ceramidase is one of the key enzymes that regulate the metabolism of ceramides and glycosphingolipids, which are important members of the SphL family. Herein, we describe the lead optimization studies of benzoxazolone carboxamides resulting in piperidine 22m, where we demonstrated target engagement in two animal models of neuropathic lysosomal storage diseases (LSDs), Gaucher's and Krabbe's diseases. After daily intraperitoneal administration at 90 mg kg-1, 22m significantly reduced the brain levels of the toxic lipids glucosylsphingosine (GluSph) in 4L;C? mice and galactosylsphingosine (GalSph) in Twitcher mice. We believe that 22m is a lead molecule that can be further developed for the correction of severe neurological LSDs where GluSph or GalSph play a significant role in disease pathogenesis.
2-Aminobenzoxazole ligands of the hepatitis C virus internal ribosome entry site
Rynearson, Kevin D.,Charrette, Brian,Gabriel, Christopher,Moreno, Jesus,Boerneke, Mark A.,Dibrov, Sergey M.,Hermann, Thomas
, p. 3521 - 3525 (2014/07/22)
2-Aminobenzoxazoles have been synthesized as ligands for the hepatitis C virus (HCV) internal ribosome entry site (IRES) RNA. The compounds were designed to explore the less basic benzoxazole system as a replacement for the core scaffold in previously discovered benzimidazole viral translation inhibitors. Structure-activity relationships in the target binding of substituted benzoxazole ligands were investigated.
