Facile synthesis of fused pyrazolo[1,5-a]pyrimidinepyrazolo [1,5-a]triazines and N-sulphonamidopyrazoles as antiinflammatory.
Interaction of hydrazine hydrate with methyl (2-E)-2-cyano-3-[(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)amino]-3-(methylsulphanyl)-2-propenoate 2 which was obtained by the reaction of methyl-2-cyano-3,3-bis(methylsulphanyl) acrylate 1 with 4-amino-1-phenyl-2,3-dimethyl pyrazoline-5-one afforded methyl-5-amino-3-[(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)amino]-1H-pyrazole-4-carboxylate 3a. The pyrazolin derivative 3a is a good precursor for the synthesis of pyrazolo[1,5-a]pyrimidines which is based on the interaction of 3a with alpha,beta-unsaturated nitrile derivatives. The biological effects of some of the newly synthesized compounds were also investigated as antiinflammatory, analgesic and antipyretic drugs. Compounds 2b, 4a, 3a, 3b, 2a and 4b were found to have significant antiinflammatory activity in descending order in comparison to control groups phenylbutazone. Compounds 3a, 2a, 4b, 4a, 2b and 3b have analgesic activity in decreasing order. Compound 3a was the most potent and had 82.6% potency of Novalgin. Compounds 2b, 2a, 3b, 4b, 3a and 4a were found to have significant antipyretic activity in descending order. Compounds 2a, 4b induced no ulcerogenic activity, while compounds 3b, 2b, 4a and 3a showed only slight ulcerogenic activity.
Fathalla
O A
OA
Medicinal Chemistry Department, National Research Centre, Dokki, Cairo, Egypt.
Zaki
M E A
ME
Swelam
S A
SA
Nofal
S M
SM
el-Eraky
W I
WI
D000700:Analgesics / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D002351:Carrageenan; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D005334:Fever / Q000139:chemically induced / Q000517:prevention & control; D008401:Gas Chromatography-Mass Spectrometry; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D010147:Pain Measurement; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000139:chemically induced / Q000473:pathology; D014227:Triazines / Q000138:chemical synthesis* / Q000494:pharmacology*
D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D007202:Indicators and Reagents; D011720:Pyrazoles; D014227:Triazines; D002351:Carrageenan