MEDI 453 |
| Gabapentin (Neurontin®) and pregabalin (Lyrica®) are highly effective in the treatment of neuropathic pain mediating their mode of action via an interaction with a binding site located on the α2δ subunit of a calcium channel. We have synthesized a number of 5-membered ring analogues of gabapentin, several of which show improved potency. Bicyclic analogue (i) has superior potency to gabapentin and pregabalin and has also proven to have superior efficacy to gabapentin and pregabalin in a key in vivo model of neuropathic pain. Synthesis of the regioisomers of this molecule led to the identification of the similarly potent and efficacious (ii). Both molecules have similar pharmacokinetic profiles to gabapentin. These compounds have progressed into clinical trials.
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General Oral Session
9:00 AM-12:20 PM, Thursday, August 23, 2007 BCEC -- 210B, Oral
Division of Medicinal Chemistry |
