Phenyl(thio)phosphon(amid)ate benzenesulfonamides as potent and selective inhibitors of human carbonic anhydrases II and VII counteract allodynia in a mouse model of oxaliplatin-induced neuropathy
Human carbonic anhydrase (CA; EC 4.2.1.1) isoforms II and VII are implicated in neuronal excitation, seizures, and neuropathic pain (NP). Their selective inhibition over off-target CAs is expected to produce an anti-NP action devoid of side effects due to promiscuous CA modulation. Here, a drug design strategy based on the observation of (dis)similarities between the target CA active sites was planned with benzenesulfonamide derivatives and, for the first time, a phosphorus-based linker.