Synthesis and pharmacological evaluation of N-phenyl-acetamide sulfonamides designed as novel non-hepatotoxic analgesic candidates.

Abstract In this paper we report the design, synthesis and pharmacological evaluation of a series of N -phenyl-acetamide sulfonamide derivatives ( 5a – g ), planned by structural modification on the prototype paracetamol ( 1 ). In this series ( 5a – g ), compound LASSBio-1300 ( 5e ; ID 50  = 5.81 μmol/kg) stands out as a new non-hepatotoxic analgesic drug candidate. The increase of area, volume and eletrostatic potential of paracetamol's analogues seems to be beneficial to the analgesic activity. Unlike paracetamol ( 1 ) and the other analogues ( 5a , 5d – g ), compounds 5b and 5c presented an important anti-hypernociceptive activity associated to inflammatory pain.