Chalcones or 1,3-diaryl-2-propen-1-ones are known to be useful for treating pain, inflammation, and certain diseases although their uses have not been scientifically verified. Due to the limitations of opioid and NSAID therapy, there is a continuing search for new analgesics. A series of novel new 1-phenyl-3-{4-[(2E)-3-phenylprop-2-enoyl]phenyl}-thiourea and urea derivatives were synthesized and evaluated against writhing test in mice, following the aromatic substitution pattern proposed by Topliss. The results of the preliminary bioassays indicate that compound 3 presents promising anti-nociceptive activity in acetic acid-, formalin-, and glutamate-induced pain in mice, compared with some well-known non-steroidal anti-inflammatory and analgesic drugs.