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New heterocycle derivatives useful for the treatment of neurodegenerative diseases



Statut des brevets

Priority patent application  N°FR0854921 filed on July 07, 2008 and entitled “Dérivés hétérocycliques utiles dans le traitement des maladies neurodégénératives”



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Collaboration Agreement  and  Exclusive license


Laboratoire de Pharmacognosie, (BiOCIS, UMR8076), Chatenay-Malabry, France.



Neurotrophic factors have been shown to possess strong neuroprotective and neurorestaurative properties in neurodegenerative disease. However the issues to control their delivery into the lesioned areas of the brain and their surgical administration, linked to their inability to cross the blood brain barrier, are many drawbacks responsible of undesirable side effects limiting their clinical use. A strategy implying the use of neurotrophin-like small molecules could provide an interesting therapeutic alternative avoiding neurotrophin administration and its side effects. In an attempt to develop drugs mimicking endogenous neurotrophic factors, we have designed and synthesized low molecular weight molecules that exhibit neuroprotective and neuritogenic properties.


A cell-based screening of an in-house compound collection led to the characterization of compounds exhibiting both activities in the nanomolar range on mesencephalic dopaminergic (DA) neurons in spontaneous or MPP+-induced neurodegeneration. This study provides evidence that rescued neurons possess a functional DA transporter. Furthermore these results underline the involvement of the extracellular signal-regulated kinase 1/2 signaling pathway in these processes.
The most potent neurotrophic compounds were able to cross the blood brain barrier and are denied of any toxic effect on preliminary in vivo studies on mice, when administrated per os or intra-peritoneal.

Specificity studies on different neurons and related cell lines (Gabaergic, astrocytes, etc…) will be performed to determine the potential of the most active compounds.

Blood brain barrier penetration and compound localization will be studied by in vivo and ex vivo imaging.
In vivo studies are being performed on 6-OHDA lesioned rats and MPTP intoxicated mice, two most pertinent animal models of Parkinson disease.


These compounds, by their biological properties, present a very promising profile for the first curative treatment of neurodegenerative diseases such as Parkinson disease. They are easy to synthesize, denied of any cytotoxicity at the CI5 of 10 nM, do not show toxicity in mice on a chronic treatment at 300 mg/kg/day (for 15 days). They present physical-chemical properties compatible for penetration of the BBB, as demonstrated by ex vivo HPLC/MS analyses.
The economical interest for such a treatment is important since it is estimated that more than 29 millions of people in the world are facing a neurodegenerative disease and this is in constant increase.


These new derivatives can be used alone or in association with known drugs for the treatment of Alzheimer disease, Parkinson disease, Multiple Sclerosis or Cerebral Vascular Accidents.

For further information, please contact us (Ref 02056-01)

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