Hiroki Kakuta and colleagues, Okayama University, Japan, previously found that N-(4-aminophenyl)-4-trifluoromethylbenzamide (TFAP), a COX-1 inhibitor, exhibits an analgesic effect without causing gastric damage. Unfortunately, TFAP causes reddish purple coloration of urine, and its analgesic effect is less potent than that of indomethacin.
They now describe the development of 4- and 5-amino-2-alkoxy-N-phenylbenzamide scaffolds, designed on the basis of the structures of TFAP and parsalmide, another known COX-1 inhibitory analgesic agent. 5-Amino-2-ethoxy-N-(2-methoxyphenyl)benzamide and 5-amino-2-ethoxy-N-(3-trifluoromethylphenyl)benzamide possessed potent COX-1 inhibitory and analgesic activities, similar to or above those of indomethacin. The fluorinated compound did not cause gastric damage or coloration of urine.
These compounds appear to be promising candidates for analgesic agents and are attractive lead compounds for further development of COX-1 inhibitors.
- Design and Synthesis of Novel Cyclooxygenase-1 Inhibitors as Analgesics: 5-Amino-2-ethoxy-N-(substitutedphenyl) benzamides
R. Fukai, X. Zheng, K. Motoshima, A. Tai, F. Yazama, H. Kakuta,