Adrenergic receptors, belong to the G-protein coupled receptors (GPCRs) super family, which mediate the actions of endogenous catecholamines (epinephrine and norepinephrine). They are categorized into a1, a2, and �receptors. a2C receptors (a subtype of a2) are broadly present in both the CNS and peripheral organs. It's known for many years that non-selective a2 agonists such as clonidine and dexmedetomidine can produce clinically effective analgesia. a2C receptors are located primarily on primary afferent terminals and interneurons in lamina I and II. They are positioned to reduce transmitter release and central sensitization as well as enhance inhibition of pain perception. Biological studies suggest that selective and brain-penetrating a2C agonists can be a potential treatment for neuropathic pain without a-adrenergic receptor mediated adverse effect. Herein, we disclose the synthesis and SAR studies of the conformational restricted chroman series. Analogs from the chroman series display excellent in vivo efficacy in our rat spinal nerve ligation (SNL) model.

(Imidazolylmethylene)chroman, a potent, selective, and conformationally restricted α2c agonist, for the treatment of neuropathic pain

244th National Meeting (2012)

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