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

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; ID50 = 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.

In this paper we report the design, synthesis and pharmacological evaluation of a series of N-phenyl-acetamide sulfonamide derivatives, planned by structural modification on the prototype paracetamol.Figure optionsDownload as PowerPoint slide