Lead Optimization of L0X2Z18B: a new drug candidate for Parkinson's Disease
01 / 2007 - 12 / 2008
Nederlandse Organisatie voor Wetenschappelijk Onderzoek - NWO
Parkinson's Disease (PD) is a movement disorder that is chronic and progressive. PD occurs when specific cells of the brain malfunction and die. These cells produce dopamine, which is a chemical messenger (neurotransmitter), that send information to parts of the brain responsible for controlling movement and coordination. When a person has PD, their dopamine-producing cells begin to die and the amount of dopamine produced in the brain decreases. The pharmacological treatment of PD has been dominated by dopamine agonists (?functional mimics?). However, long-term treatment of PD with these agonists can cause side-effects. Dopamine agonists target G-protein-coupled receptors (GPCRs), which are one of the largest families of mammalian cell-surface receptors. Since the mid-90?s it is known that these GPCR?s can have multiple sites were agonists and antagonists can bind. Furthermore, it is known that adenosine antagonists are beneficial in the treatment of PD. These features were combined in a new methodology to treat PD. New drugs are being developed, which posses an adenosine antagonist as well as dopamine agonist in one molecule. These two components can bind to the GPCRs simultaneously. The host group has carried out the development of a lead compound, which shows good activities in preliminary binding studies. This research project focuses on the structural optimization of the lead compound.