Design, synthesis and biological evaluation of new small molecules for treatment of Amyotrophic Lateral Sclerosis

Abstract

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that leads to the death of motor neurons in the brain stem, spinal cord, and cortex. Currently, there is a lack of effective therapies for ALS. Superoxide dismutase (SOD1) is a hallmark of ALS in both familial and sporadic patients in Asia. The isoquinoline derivatives significantly improve axon recovery in the overexpression of SOD1G93A zebrafish model. Among them, compound 7 showed moderate axon recovery. Furthermore, compound 7 exhibited BBBpermeability, liver microsomal stability, and no inhibition of hERG