Abstract
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•Novel 4-oxo-spirochromanes bearing the primary sulfonamide group as CAIs are reported.•Strong inhibition on the hCA II and VII isoforms were observed.•Compounds 6d and 6l showed comparable pain threshold level to AAZ in an in vivo model of the disease.
A novel series of 4-oxo-spirochromane bearing primary sulfonamide group were synthetized as Carbonic Anhydrase inhibitors (CAIs) and tested for their management of neuropathic pain. Indeed, CAs have been recently validated as novel therapeutic targets in neuropathic pain. All compounds, here reported, showed strong activity against hCA II and hCA VII with KI values in the low or sub-nanomolar range. Two compounds (6d and 6l) showed good neuropathic pain attenuating effects and longer duration than drug reference acetazolamide in an animal model of oxaliplatin induced neuropathy.