Synthesis and biological evaluation of amide derivatives of (5,6-dimethoxy-2,3-dihydro-1H-inden-1-yl)acetic acid as anti-inflammatory agents with reduced gastrointestinal ulcerogenecity.
A variety of amide derivatives of (5,6-dimethoxy-2,3-dihydro-1H-inden-1-yl)acetic acid were synthesized and screened for their analgesic and anti-inflammatory activities. The compounds were found to have longer activity profile exceeding that of indomethacin in carrageenan-induced rat paw edema model. Few selected compounds were also screened for their antipyretic, anti-arthritic and ulcerogenecity potential. From these studies it can be concluded that these compounds though have significant antipyretic activity did not act through the inhibition of TNF-alpha. The test compounds failed to prevent the development of secondary inflammation in adjuvant-induced arthritis assay. However, these compounds showed no ulcer formation at the tested dose level of 100 mg/kg p.o.
Sharma
Meenakshi
M
Medicinal Chemistry Research Laboratory, Pharmacy Group, Birla Institute of Technology and Science, Pilani-333031, Rajasthan, India.
Ray
S M
SM
D000085:Acetates / Q000009:adverse effects / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000627:therapeutic use; D000577:Amides / Q000737:chemistry*; D018712:Analgesics, Non-Narcotic / Q000009:adverse effects / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000627:therapeutic use; D001168:Arthritis / Q000188:drug therapy; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced*; D007192:Indenes / Q000009:adverse effects / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000627:therapeutic use; D007249:Inflammation / Q000188:drug therapy; D011335:Proadifen / Q000494:pharmacology; D051381:Rats; D014456:Ulcer / Q000139:chemically induced*
C525799:5,6-dimethoxy-2,3-dihydro-1H-inden(-1-yl)acetic acid; D000085:Acetates; D000577:Amides; D018712:Analgesics, Non-Narcotic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004791:Enzyme Inhibitors; D007192:Indenes; D011335:Proadifen