Design, synthesis and pharmacological evaluation of a series of 5-carbethoxy-4-chloro-6-(substituted amino)pyrimidines as potential analgesic and anti-flammatory agents with very low ulcerogenic potential.
A series of 5-carbethoxy-4-chloro-6-(substituted amino)pyrimidines was designed on the basis of its good 3-dimensional structural similarity with mefenamic acid (CAS 61-68-7), a well known anti-inflammatory drug. Synthesis of some 5-carbethoxy-4-chloro-6-(substitutedamino)pyrimidines has been achieved by cyclization of N-(cyanovinyl)formamidine intermediate in the presence of dry HCl. Target compounds were evaluated for their analgesic and anti-inflammatory potential by known experimental models. Some of the compounds emerged as more potent analgesic and anti-inflammatory agents than the standard drug diclofenac sodium (CAS 15307-79-6). A very low ulcer index was observed with the most potent compound.
Chhabria
Mahesh T
MT
Department of Pharmaceutical Chemistry, L. M. College of Pharmacy, Navrangpura, Ahmedabad, Gujarat, India. mahesh.chhabria@rediffmail.com
Shishoo
Chamanlal J
CJ
Vaghela
Dilip K
DK
Patel
Shailesh M
SM
Satia
Milan C
MC
D000588:Amines / Q000138:chemical synthesis* / Q000494:pharmacology*; D018712:Analgesics, Non-Narcotic / Q000009:adverse effects / Q000138:chemical synthesis* / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000138:chemical synthesis* / Q000494:pharmacology*; D002351:Carrageenan; D015195:Drug Design; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D005260:Female; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008958:Models, Molecular; D010147:Pain Measurement; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013055:Spectrophotometry, Infrared; D013276:Stomach Ulcer / Q000139:chemically induced* / Q000473:pathology
D000588:Amines; D018712:Analgesics, Non-Narcotic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D011743:Pyrimidines; D002351:Carrageenan