Design and synthesis of niflumic acid-based N-acylhydrazone derivatives as novel anti-inflammatory and analgesic agents

作者：Kheradmand Amin; Navidpour Latifeh^*; Shafaroodi Hamed; Saeedi Motahar Ghazaleh; Shafiee Abbas

来源：Medicinal Chemistry Research, 2013, 22(5): 2411-2420.

DOI：10.1007/s00044-012-0235-3

• Niflumic acid hydrazide
• Anti-inflammatory
• Analgesic

A new series of niflumic acid-based N-acylhydrazone derivatives 5a-p were synthesized and evaluated for their anti-inflammatory and analgesic activities. Most of the compounds have shown anti-inflammatory activity with a moderate-to-excellent activity range (20-80 % reduction in inflammation). Among them, 3-chlorophenyl 5d and 3-pyridyl derivatives 5o exhibited the most potent anti-inflammatory activity relative to niflumic acid as the reference drug (77, 76, and 70 % reduction in inflammation at 1-h postdrug administration, respectively). Also, molecular simplification of niflumic acid through replacing the N-aryl group with N-methyl group produced compounds 6a-f with anti-inflammatory activity in a quite similar manner to those of their parent derivatives. In this subgroup, 4-pyridyl derivative 6f showed the most potent anti-inflammatory activity relative to niflumic acid (80 % reduction in inflammation at 1-h postdrug administration). The compounds with highest anti-inflammatory activity were subjected to analgesic assays and showed moderate-to-excellent analgesic activities. The compound 5j, 4-methoxy derivative, exhibited the highest analgesic activity relative to niflumic acid (97 and 68 % activity, respectively).

• 出版日期2013-5