Discovery, Synthesis, and Characterization of an Orally Bioavailable, Brain Penetrant Inhibitor of Mixed Lineage Kinase 3

Inhibition of mixed lineage kinase 3 (MLK3) is a potential strategy for treatment of Parkinson’s disease and HIV-1 associated neurocognitive disorders (HAND), requiring an inhibitor that can achieve significant brain concentration levels. We report here URMC-099 (1) an orally bioavailable (F = 41%),...

Ausführliche Beschreibung

Gespeichert in:

Bibliographische Detailangaben
Veröffentlicht in:	Journal of medicinal chemistry 2013-10, Vol.56 (20), p.8032-8048
Hauptverfasser:	Goodfellow, Val S, Loweth, Colin J, Ravula, Satheesh B, Wiemann, Torsten, Nguyen, Thong, Xu, Yang, Todd, Daniel E, Sheppard, David, Pollack, Scott, Polesskaya, Oksana, Marker, Daniel F, Dewhurst, Stephen, Gelbard, Harris A
Format:	Artikel
Sprache:	eng
Schlagworte:	Administration, Oral Animals Area Under Curve Biological Availability Blood-Brain Barrier - metabolism Brain - metabolism Carbazoles - chemical synthesis Carbazoles - pharmacokinetics Carbazoles - pharmacology Cells, Cultured Cognition Disorders - complications Cognition Disorders - prevention & control Drug Discovery - methods HIV Infections - complications Humans JNK Mitogen-Activated Protein Kinases - metabolism Male MAP Kinase Kinase Kinases - antagonists & inhibitors MAP Kinase Kinase Kinases - metabolism Mice Mice, Inbred C57BL Mitogen-Activated Protein Kinase Kinase Kinase 11 Models, Chemical Molecular Structure Monocytes - drug effects Monocytes - metabolism Phosphorylation - drug effects Protein Kinase Inhibitors - chemical synthesis Protein Kinase Inhibitors - pharmacokinetics Protein Kinase Inhibitors - pharmacology Pyridines - chemical synthesis Pyridines - pharmacokinetics Pyridines - pharmacology Pyrroles - chemical synthesis Pyrroles - pharmacokinetics Pyrroles - pharmacology tat Gene Products, Human Immunodeficiency Virus - pharmacology Tumor Necrosis Factor-alpha - metabolism
Online-Zugang:	Volltext
Tags:	Tag hinzufügen Keine Tags, Fügen Sie den ersten Tag hinzu!

Schreiben Sie den ersten Kommentar!