MEDI 43 |
| The exclusive expression of 5-HT6 receptor in the brain makes it a target of choice for CNS mediated disorders like Alzheimer's, Parkinson's disease, Dementia and other Neurodegenerative disorders. Some attempts are in progress for the clinical proof of concept for 5-HT6 antagonists as a new therapeutic class. Structure 1 was previously reported by us at Suven as potent, safe, highly selective and orally bioavailable 5-HT6 receptors antagonist. In order to explore the SAR scope and potentially to improve pharmacokinetic/pharmacodynamic, and CNS penetration properties of the molecules, -CH2-piperazine in structure 1 was moved from C3 of indole to C4 of indole. Structure 2 gave a series of novel and potent 5-HT6 receptor antagonists with Ki in the range of 1-5 nM, when tested by the in-vitro radio-ligand binding assays. Synthesis of these molecules, binding affinity and selectivity as well as some functional data will be presented along with computational analysis.
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Poster Session
7:00 PM-9:00 PM, Sunday, August 19, 2007 BCEC -- Exhibit Hall - B2, Poster
Division of Medicinal Chemistry |
