Indian Journal of Chemistry Vol. 38B, June 1999, pp. 684 - 695 Synthesis and pharmacological evaluation of some novel 5-aryl-6- arylamino-l-phenylpyrazolo[3,4-dlpyrimidin-4(5H)-ones as analgesic and anti-inflammatory agents Chamanlal J Shishoo*, Urvish S Pathak, Ishwarsinh S Rathod, Kishore S Jain, Laxmivenkatesh G Nargund, Ashok D Taranalli t , Hiren Patel, Vivek Kumar & Vikas S Shirsath. Department of Pharmaceutical Chemistry, L.M.College of Pharmacy, Navrangpura, Ahmedabad 380 009 t H.Q.K.L.E.'s College of Pharmacy, J.N.Medical College Campus, Belgaum 590 OW, India. Received 23 February 1998; accepted (revised) 24 November 1998 A series of novel title compounds 4a-o has been synthesized through two different synthetic routes. Whi le the first involves the condensation of pyrazole o-aminoester 1 with aryl isothiocyanates 2, the second involves cyciocondensation 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 analgesic activity comparable to morphine and aspirin at the dose levels of 10 mg/kg 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 test. Efforts towards optimization of lead compound 4c have resulted in identifying more active compounds. Compounds 4b, 4c, 4e, 4h, 4i and 40 exhibit anti- inflammatory activity superior to aspirin at 100 mg/kg, p.o. in the colton pellet induced granuloma test(rats); compound 40, is also found to be superior to aspirin when evaluated by the carageenan induced rat paw edema test. Acute toxicity studies reveal that these compounds are non-toxic upto 4.0 g/kg, p.o. in mice. The lead compound, 4.:, has been fo und to be safe and without any untoward effects in the 30, as well as, 60 days chronic toxicity studies in mice. Non-narcotic analgesic and anti-inflammatory drugs represent one of the most widely prescribed categories of drugs'. NSAIDs are used extensively not only in rh eumatology but also in other fields of medicine like treatment of gout, gynaecology and paediatrics 2 • Most of the drugs in therapeutic use have a drawback of bearing an acidic functionality and therefore the side effects associated with it. More or less, all the NSAIDs and OTe analgesics suffer from adverse side effects like allergic reactions, GIT disturbances, irritation, nausea, vertigo, drowsiness. dizziness etc. In order to circumvent these problems, extensive search for an ideal NSAID still continues. The pyrazolo[3,4-d]pyrimidines have been described as biologically active agents. 305 The most X I, )l ;:-( 'N N R I ,R=H.X=O II, R = H, X = S HO III , R = OH. X = 0 IV H OHOH widely used pyrazolo[3,4-d]pydmidines, allopurinol I, thiopurinol nand oxyallopurinol III are established inhibitors of xanthine oxidase and thus in terfere in the biosynthesis of uric acid, the causative agent of gout. This group of compounds also exhibits antineoplastic activitl. Antitumour and antiviral co mpounds have been synthesized based on the antibiotic formycin IV, a nucleoside of pyrazolo[3,4-d]pyrimidine 7 . Potent anti-inflammatory aDd analgesic activities have been reported in a number of 5-arylpyrazolo[3,4- d]pyrimidines V and VI 8 . 9 • Herein, we report the synthesis, analgesic and anti- inflammatory activities and results of our toxicity studies of novel 5-aryl-6-aryla mino-I-phenylpyra- v VI