N-aryl-N'-ureido-O-sulfamates: Potent and selective inhibitors of the human Carbonic Anhydrase VII isoform with neuropathic pain relieving properties.

• An efficient synthesis of N -aryl- N' -ureido- O -sulfamates (AUS s) is reported. • AUS are a new class of CAIs with low nanomolar potencies against the human CA VII. • Modeling deciphered the features behind the selective inhibitory profile of AUS. • A selection of AUS showed promising neuropathic pain modulating effects on animals. Herein we report for the first time an efficient synthetic procedure for the preparation of N -aryl- N' -ureido- O -sulfamates (AUS s) as a new class of Carbonic Anhydrase Inhibitors (CAIs). The compounds were tested for the inhibition of several human (h) Carbonic Anhydrase (CA; EC 4.2.1.1) isoforms. Interesting inhibition activity and high selectivity against CA VII and XII versus CA I and II, with K I s in the low nanomolar range, were observed. Molecular modeling studies allowed us to decipher the structural features underpinning the selective inhibitory profile of AUSs towards isoforms CAs VII and XII. A selection of sulfamates showed promising neuropathic pain modulating effects in an in vivo animal model of oxaliplatin induced pain. [ABSTRACT FROM AUTHOR]