Furoxans as Novel Therapeutics for Neurodegenerative Disorders

Description:

Project ID:  D2017-15

 

Background

Nitric oxide (NO) signaling plays a major role in brain activity and normal function of neurons. Disrupted NO signaling is implicated in several central nervous system (CNS) and neurodegenerative disorders. NO mimetic, such as nitrates, have been used against a variety of neurological disorders. This is due to the ability of the nitrates to enhance NO-related signaling. Alzheimer's disease (AD) is the most common form of neurodegenerative disease, estimated to affect 36 million people worldwide, with major affected population in North America and Europe. Unfortunately, development of nitrates for neurodegenerative disorders such as AD, stroke has faced several challenges, such as poor metabolic stability, an inability to effectively monitor the level of the nitrates, and formulation instability in the presence of atmospheric humidity.

Invention Description

Researchers at the University of Toledo have designed and synthesized patented furoxan compounds that is capable of sustained delivery of NO.   

Applications

  • The furoxans can be used for treating multiple neurodegenerative and neurological disorders, including Alzheimer’s disease (AD), stroke, traumatic brain injury (TBI), and chronic traumatic encephalopathy (CTE) and depression.
  • The compounds can also be used to reverse memory impairment.
  • The furoxans can be used to provide neuroprotective and neuro-restorative effects following incidences of acute neuronal insults such as concussions and strokes.

Advantages

  • The novel furoxans are distinct from previous molecules based on a unique understanding of furoxan mechanistic reactivity, experience in NO mimetic CNS drug discovery, and data reporting in vivo furoxan efficacy in relevant preclinical animal models of memory and neurodegeneration.
  • Novel findings include both in vivo memory improvement and neuro-restorative effects in a stroke model.
  • The furoxans exhibited brain bioavailability with enhanced memory improvement and neuroprotective activity in a cellular model of ischemia.
  • The novel furoxans were synthesized using a novel, scalable synthetic method.
  • The furoxans exhibit appropriate physiochemical properties, based on novel well-defined design criteria, to produce favorable CNS penetration.
  • In vitro and in vivo data is available, including data related to target pathway engagement pharmacodynamics and pharmacokinetics.

 

IP Status:

 

Publications:

US Patent 10590119

 

Schiefer IT, et al., Furoxans (1,2,5-oxadiazole-N-oxides) as novel NO mimetic neuroprotective and precognitive agents. Journal of Medicinal Chemistry, 2012, 3076-3087

 

VHorton A, et al., Furoxans (Oxadizaole-4N-oxides) with attenuated reactivity are neuroprotective, cross the blood brain barrier, and improve passive avoidance memory. Journal of Medicinal Chemistry, 2018, 4593-4607

 

 

 

 

Patent Information:
Category(s):
Neuroscience
For Information, Contact:
Lokesh Mohan
Licensing Associate
The University of Toledo
419-530-6231
lokeshwar.mohan@utoledo.edu
Inventors:
Isaac Schiefer
Zahoor Shah
Keywords:
Alzheimer's
Depression
Encephalopathy
Furoxan
Neurodegenerative
Nitrate
NitricOxide
Stroke
Traumatic