Out-licensing

Nitrone derivatives with high cell permeability, and in vitro antioxidant and neuroprotective activity higher than known nitrones are drug candidates against ictus, ischemia and other neurodegenerative diseases

A new approach to develop drugs for the treatment of Ictus and Ischemia

The use of nitrone derivates represents a new and interesting approach for the treatment of diseases like Ictus or Ischemia, related with the oxidation of lipid membranes in neurones. The nitrone group acts as a radical scavenger and reduces oxidative stress. Known nitrones like phenyl-t-butyl nitrone (PBN) and NXY-059, show a high activity as antioxidant agents, however, at low dose, their in vivo efficacy is limited, probably due to low cell permeability. Taking into account the excellent antioxidant characteristics of nitrone compounds, the search of new derivatives with major activity and better permeability is of great interest in the area of neurodegenerative diseases.
New quinoline nitrone derivatives with elevated antioxidant activity against hydroxyl radicals and lipidic peroxidation, have been prepared by researchers from CSIC. Universidad Complutense de Madrid and Hospital Ramon y Cajal. The presence of a quinoline group in the structure of the molecules increases their lipophilicity and can improve their cell permeability. In vitro assays in cell cultures show that new compounds have also high neuroprotective activity. Furthermore, the compounds are able to cross the blood-brain barrier, which, together with their antioxidant activity, make them especially useful as drugs for the treatment of CNS diseases.

Main features and advantages

• The new compounds are able to inhibit lipidic peroxidation and show an activity as antioxidant agents against free radicals (at 100 μM, 95-100% of scavenging activity for hydroxyl radicals) higher than PBN (90%) and the antioxidant trolox (73%)
  It has been observed that new compounds have a neuroprotective effect on cells exposed to oxygen-glucose deprivation (70% of neuroprotection at 1 μM) higher than PBN (68% at 100 μM)
• In vitro assays show that the compounds are able to cross the blood-brain barrier with good permeability values (Pe= 15 10^6 cm / s) similar to the reported for verapamil (Pe= 16 10^6 / s) that is generally used as a high permeability standard
• All the compounds are prepared in a single synthetic step from commercially available starting materials following a rapid and straightforward process

Early Stage

Priority patent application filed

Exclusive patent licensing is preferred, but we are open to discuss other approaches

P201131338