Abstract
We report the development of a novel, aqueous-soluble, safe, small molecule, experimental therapeutic that suppresses injury-induced, proinflammatory cytokine increases in the brain, with resultant attenuation of synaptic protein biomarker loss and improvement in hippocampus-dependent behavioral deficits. A GMP production scheme for the active pharmaceutical ingredient, compound 17, is presented. The development and large-scale availability of this novel compound allow exploration of new, potentially disease-modifying, therapeutic approaches to CNS disorders.
Publication types
-
Research Support, N.I.H., Extramural
MeSH terms
-
Alzheimer Disease / drug therapy
-
Animals
-
Astrocytes / drug effects
-
Astrocytes / metabolism
-
Behavior, Animal / drug effects*
-
Biological Availability
-
Brain Chemistry / drug effects*
-
Chemical Phenomena
-
Chemistry, Physical
-
Cytokines / biosynthesis*
-
Drug Design
-
Glial Fibrillary Acidic Protein / biosynthesis
-
Hippocampus / drug effects
-
Magnetic Resonance Spectroscopy
-
Mice
-
Microglia / drug effects
-
Nootropic Agents / chemical synthesis*
-
Nootropic Agents / pharmacology*
-
Nootropic Agents / toxicity
-
Pyridazines / chemical synthesis*
-
Pyridazines / pharmacology*
-
Pyridazines / toxicity
-
Pyrimidines / chemical synthesis*
-
Pyrimidines / pharmacology*
-
Pyrimidines / toxicity
-
Rats
-
Synapses / drug effects*
-
Synapses / metabolism
-
Up-Regulation / drug effects
Substances
-
Cytokines
-
Glial Fibrillary Acidic Protein
-
Nootropic Agents
-
Pyridazines
-
Pyrimidines
-
minozac