Indian Journal of Chemistry Vol. 44B, February 2005, pp. 387-399 Synthesis, hydrolysis over silica column, anticancer, anti-inflammatory and analgesic activity evaluation of some pyridine and pyrazine derivatives Sham M Sondhi*, Nirupma Singh, Shefali Rajvanshi & Monika Johar Department of Chemistry, IIT Roorkee, Roorkee 247667, India E-mail: sondifcy@iitr.ernet in Rakesh Shukla & Ram Raghubir Division of pharmacology, CDRI, Lucknow 226001, India and Sunanda G Dastidar Ranbaxy Research Laboratories, New Delhi 110020, India Received 8 October 2004; accepted (revised) 9 December 2004 Various 3,4-diaryl-2-iminothiazolines 1a-s have been condensed with 4-cyanopyridine and 2-cyanopyrazine by refluxing in methanol for about 16 hr to give corresponding 3,4-diaryl-2-imino-N-(4′-pyridyliminomethyl)-4-thiazoline (2a- k, n-p) and 3, 4-diaryl-2-imino-N-(2′-pyrazinyliminomethyl)-4-thiazoline (3a-m, q-s) derivatives. In some cases when these pyridyl and pyrazinyl derivatives are purified by column chromatography over silica gel these compounds get hydrolysed to give corresponding 3,4-diaryl-2-imino-N-(4′-carbonylpyridyl)-4-thiazoline (2o,p) and 3,4-diaryl-2-imino-N-(2′- carbonylpyrazinyl)-4-thiazoline (3q-s) derivatives. The structures of all synthesized compounds have been confirmed by spectroscopic methods. Compounds 2a-c,e-h,k,n,p, 3a-i and 3l,m,q are screened for anticancer activity against a small panel of six human cancer cell lines consisting of prostate (DU 145) colon (HT 29) breast (MCF 7) breast (MCF 7/ADR), CNS (U 251) and lung large (NCIH 460) tumors. Best GI 50 values are shown by 3f, 11.5 μM (prostate tumor, cell line DU 145), 3f, 1.0 μM (colon tumor, cell line HT 29), 2n, 6.2μM (breast tumor, cell line MCF 7), 2p, 4.8μM (breast tumor, cell line MCF 7/ADR), 2p, 6.3μM (CNS tumor, cell line U 251) and 3f, 0.9 μM (lung large carcinoma, cell line NCIH 460) respectively. Compound 3f has shown good anticancer activity against three cancer cell lines, whereas compounds 2n and 2p against one and two cancer cell lines respectively. Antiinflammatory activity evaluation of 2a-k,n,o,p, 3a-m and 3q,r,s has been carried out and compounds 2a-h, 2j, 2o,p, 3a,b,c,g,m and 3r showed 13, 32.5, 48.8, 6.5, 13.9, 7.0, 4.3, 16.6, 20.0, 17.3, 27.7, 16.2, 18.4, 34.7, 15.6, 24.0 and 4.7% activity, respectively, at 100mg/kg p.o. Analgesic activity, evaluation of 2a-k,n,o,p, 3a-m and 3q,r,s indicates that these compounds possess 50, 25,75, 25, 50, 75, 50, 50, 25, 0.0, 50, 50, 0.0, 75, 50, 25, 25, 25, 75, 0.0, 25, 25, 25, 50, 50, 75, 25, 50, 75 and 50% analgesic activity at 100mg/kg p.o. IPC: Int.Cl. 7 C 07 D 211/00, 231/00 // A 61 P 35/02, 29/00, 25/04 Pyridine and pyrazine derivatives are reported to possess antiinflammatory 1-8 and anticancer activities 9-16 . In continuation of our efforts in search of potential antiinflammatory and anticancer 17-21 agents, we have synthesized a number of pyridine and pyrazine derivatives by the condensation of 4-cyanopyridine and 2-cyanopyrazine with 3,4-diaryl-2-imino-4- thiazolines and screened them for anticancer and antiinflammatory and analgesic activities which we wish to report in this paper. A number of 3,4-diaryl-2-imino-4-thiazolines 1a-s (Scheme I) were prepared by the condensation of corresponding amine hydrochlorides with phenacyl thiocyanate as reported in the literature 22 . Condensation of 3,4-diaryl-2-imino-4-thiazolines (1a-k,n,o,p) and 4-cyanopyridine were carried out by refluxing in methanol and purifying the crude products by crystallization to give condensed products 2a-k,n (Scheme I). The physical constants and spectroscopic data of 2a-k,n reported in Table I fully support the assigned structures. Condensation of 3,4-diaryl-2-imino-4-thiazolines (1a-m, q-s) with 2-cyanopyrazine by refluxing in methanol and purifying the crude products by crystallization gave condensed products 3a-m (Scheme I). Physical constants and spectroscopic data of 3a-m were found to be in full agreement with their structures and are reported in Table I.