Synthesis and pharmacological evaluation of some novel 5-aryl-6-arylamino-1-phenylpyrazolo[3,4-d]pyrimidin-4(5H)-ones as analgesic and anti-inflammatory agents

A series of novel title compounds 4a-o has been synthesized through two dif ferent synthetic routes. While the first involves the condensation of pyraz ole o-aminoester 1 with aryl isothiocyanates 2, the second involves cycloco ndensation of alkyl isothiourea ethers of sym-diarylthioureas 5 with 1. The compounds have been evaluated for analgesic, as well as, anti-inflammatory activities in rodents. The lead compound, 4c (LM-22835), exhibits analgesi c activity comparable to morphine and aspirin at the dose levels of 10 mg/k g p.o. and 100 mg/kg p.o. In the acetic acid induced writhing test, in mice , it has been found to be superior to aspirin in the rat caudal immersion t est. Efforts towards optimization of lend compound 4c have resulted in iden tifying more active compounds. Compounds 4b, 4c, 4e, 4h, 4i and 4o exhibit antiinflammatory activity superior to aspirin at 100 mg/kg, p.o. in the cot ton pellet induced granuloma test(rats); compound 4o, is also found to be s uperior to aspirin when evaluated by the carageenan induced rat paw edema t est. Acute toxicity studies reveal that these compounds are non-toxic upto 4.0 g/kg, p.o. in mice. The lead compound, 4c, has been found to be safe an d without any untoward effects in the 30, as well as, 60 days chronic toxic ity studies in mice.