Synthesis, antiinflammatory and analgesic activity of new hexahydropyrimidine derivatives.
A number of potentially active hexahydropyrimidine derivatives of pharmaceutical interest have been synthesized. Various diSchiff's bases prepared by reacting different aromatic aldehydes with 1,3-diaminopropane were suitably reduced to give their tetrahydro derivatives which were then condensed with appropriate aldehydes to give a series of hitherto unreported hexahydropyrimidines. The resulting products were evaluated by oral route for their antiinflammatory activity. The activity of compounds 11, 23 and 4 was excellent and comparable to indomethacin. In addition to oral route of administration, the antiinflammatory activity of hexahydropyrimidine derivatives was also studied topically through transdermal gels. Compounds 11, 23, 4 and 22 produced significant inhibition in edema and showed good antiinflammatory activity comparable to diclofenac sodium gel (Relaxyl gel). All these compounds were also tested for their analgesic activity and their LD50 determined. Compounds 11, 20 and 23 showed a comparable activity with aspirin. The MTD for all the compounds was found to be > 1800 mg/kg.
Khan
M S Y
MS
Department of Pharmaceutical Chemistry, Hamdard University, Hamdard Nagar, New Delhi, India.
Gupta
M
M
D019342:Acetic Acid; D000279:Administration, Cutaneous; D000284:Administration, Oral; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology*; D002351:Carrageenan; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D007202:Indicators and Reagents; D007213:Indomethacin / Q000494:pharmacology; D007928:Lethal Dose 50; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D010146:Pain / Q000139:chemically induced / Q000517:prevention & control; D010147:Pain Measurement / Q000187:drug effects; D011743:Pyrimidines / Q000737:chemistry*; D051381:Rats; D013329:Structure-Activity Relationship
D018712:Analgesics, Non-Narcotic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D007202:Indicators and Reagents; D011743:Pyrimidines; D002351:Carrageenan; D019342:Acetic Acid; D007213:Indomethacin