CSIC has patented a series of derivatives with neuroprotective activity when subjected to biological evaluation, and its use in a potential treatment of diseases in which oxidative processes play a crucial role, such as the Alzheimer’s disease.

The present invention describes the biological multiactivity exhibited by a series of compounds and its potential use for the treatment of neurodegenerative processes such as the Alzheimer's disease (AD). These compounds are derived of the nearly unknown heterocyclic system 1,4,5-dibenzo[b,f]thiadazepines-5,6-dihydro.
AD is a neurodegenerative process associated with ageing. Their initial causes remain still unclear but there are increasing evidence that they are very close to failures in the modulation of the neuronal oxidative processes. Some years later of the initial biochemical malfunctions begin the characteristic symptoms of the disease, basically provoked by a reduction of the cholinergic neurotransmission.

The metabolism of the brain generates a high amount of toxic free radicals, but the neurons are provided with their own defence mechanisms in order to eliminate these radicals. This antioxidant system fails in AD conditions, the concentration of the free radicals increases and, as a consequence, this oxidative stress induces the rest of the processes associated to AD: aggregation of the proteins amyloid and tau, increase of the citosolic calcium concentration which produces cellular death, impairment of the cholinergic neurotransmission and, finally, massive neuronal loss and death.

As a summary, the AD is the consequence of several associated aberrant processes and the oxidative stress looks to play a crucial role as the initial source of the following failures that produce, in a more advanced stage, the well known devastating symptoms. Thus, it would be desirable to have molecules with neuroprotective and antioxidant activities, in order to modulate the concentration of free radicals situated in the origin of the disease.

The series of compounds described in this patent fill these conditions because they are small molecules showing several simultaneous activities. They are able to attack more than one aberrant process in AD as they are antioxidants and neuroprotectants at different neuronal levels and modulators of the cytosolic calcium concentration. Moreover, they are able to cross the blood-brain barrier, an essential quality for any drug to act in the central nervous system. All these features made them very attractive compounds for a treatment of the AD.
In addition, taking into account their molecular structure, it could be expected that these series of derivatives display other biological properties with potential utility as antihistaminic and antipsychotic agents.

Moreover, the effect of the drugs currently commercialised produce only a temporal relief of the symptoms. The multifunctional aspect of the patented compounds as antioxidants, neuroprotectants and modulators of the concentration of the cytosolic calcium could allow them to slow or even stop the neurodegeneration while the symptoms are also reduced or even eliminated.

Early Stage

Priority patent application filed.

This patent could be of interest to pharmaceutical companies, specially those working in the neurodegenerative sector.