MEDI 467 |
| Norepinephrine (NE) is a major neurotransmitter, which regulates body functions in both the central and peripheral nervous systems. Norepinephrine reuptake inhibitors (NRIs) increase extra cellular availability of the neurotransmitter by blocking its reuptake into the cell. Drugs that possess norepinephrine reuptake inhibition, either selectively or in combination with serotonin reuptake inhibition, have been approved for multiple indications including major depressive disorder (MDD), attention deficit hyperactivity disorder (ADHD), and pain disorders such as diabetic neuropathy and fibromyalgia. Other indications, including stress urinary incontinence (SUI) and vasomotor symptoms (VMS), are currently being assessed in clinical trials. Previously, we reported the identification of WAY-256805 as a selective norepinephrine reuptake inhibitor that exhibited activity in a variety of in vivo models. Optimization of this structure for enhanced brain penetration by improved metabolic stability (rat oral bioavailability 49%) and lipophilicity has led to the discovery of WAY-260022. We will report the structure-activity relationships of this scaffold leading to the proposed development of WAY-260022 as a selective NRI for the treatment of neurological disorders and dysfunction.
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General Oral Session
1:30 PM-4:50 PM, Thursday, August 23, 2007 BCEC -- 210A, Oral
Division of Medicinal Chemistry |
