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We are aiming in this work to synthesize target molecules not only possess antitumor activities but also kinase inhibitors. The target molecules were obtained from dimedone, which reacted with triethoxymethane to produce a product that is capable for many heterocyclization reactions to give fused pyrazole, thiophene and isoxazole derivatives. Compounds 7b, 7c, 7d, 9b, 11, 12c, 12d, 14b, 16b, 17c, 17d, 18c, 18d, and 18e were the most cytotoxic compounds, their further tests toward the five tyrosine kinases c-Kit, Flt-3, VEGFR-2, EGFR, and PDGFR and Pim-1 kinase showed that compounds 7b, 7d, 11, 12c, 14b, 16b, 17d, 18d, and 18e were the most potent of the tested compounds toward the five tyrosine kinases and compounds 7b, 7d, 14b, 16b, and 18e were of the highest inhibitions toward Pim-1 kinase. PAINS the most cytotoxic compounds showed zero PAINS alert, therefore, these compounds can be used as useful drugs in the future.

Various 1,2,4 trisubstituted imidazolin-5-one derivatives were synthesized and evaluated for their inhibitory activity against p38 mitogen-activated protein kinase (p38MAPK) and carbonic anhydrase (CA) enzymes aiming to explore potential dual inhibitors. Results revealed that compounds 3c, 3g, 3h, 4a, 6c and 6d were the most effective derivatives against p38αMAPK (IC50 = 0.14, 0.14, 0.056, 0.14, 0.13 and 0.14 μM, respectively) compared to sorafenib (IC50 = 1.58 μM) as standard drug. On the other hand, compound 4a revealed the best inhibitory activity against all the tested carbonic anhydrase isoforms CA I, II, IV and IX with Ki values of 95.0, 0.83, 6.90 and 12.4 nM, respectively compared to acetazolamide with Ki values 250, 12.1, 74 and 12.8 nM, respectively. Therefore, compound 4a can be considered as a potent dual p38αMAPK/CA inhibitor.

Schistosomiasis is considered one of the most important human helminth infection in terms of morbidity and infectivity (Chitsulo et al. Acta Trop 2000, 77, 41; Engles et al. Acta Trop 2002, 82, 139; Shelly et al. Mol Biochem Parasitol 1993, 60, 93). Derivatives of 2-amino-5-nitrothiazoles have shown activity against Schistosoma mansoni (S. mansoni) and Schistosoma haematobium (S. haematobium), but due to their toxic effect we synthesized new derivatives of a heteroaromatic amine with thiazole moiety. Required thiazole derivatives were prepared via 1 and 2. In this work, two batches of animals were used to test the efficacy of 10 derivatives of thiazole against schistosomiasis. The first batch of Swiss albino mice was infected with S. mansoni and was treated with 5 × 50 mg/kg b.w. The second batch of golden hamsters was infected with S. haematobium and was treated with 5 × 100 mg/kg b.w. Parasitological parameters, biochemical studies, and granuloma diameter were estimated. Results indicated that in the case of S. mansoni infected mice, compounds 2 (2-amino-4-thiazoliniminium chloride) and 20 (2,4-diamino thiazole) showed moderate efficacy (50% worm reduction). While compounds 18 (4-dicyanomethylene-4, 5-dihydrothiazo-2-yl)-N,N-dimethylimidoformamide) and 21 2-(dimethylamino) methylene-1,3-thiazol-4-yl)-N,N-dimethylimidoformamide) showed 83% and 90% worm reduction with some normalization of liver function and significant reduction in hepatic granuloma diameters. In the case of S. haematobium infected hamsters, compound 15 showed reduction of worms by about 50% with improvement in kidney function. The high effect of compounds 18 and 21 compared to 2, 15, and 20 could be attributed to the dimethylimidoformamide moieties combined with the thiazole ring. © 2005 Wiley Periodicals, Inc. Heteroatom Chem 16:121–222, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20072

A new synthesis of 1,3,4-thiadiazoles has been achieved. The reactivity of certain alkylheterocycles towards electrophilic reagents are reported.

The pyrazolo[3,4-b]pyridine derivatives 3 could be prepared by condensing compounds 1 with the 3-aminopyrazolone derivative 2. The pyrazolo[5,2-b]-1,3-oxazine derivative 11 and polyfunctionally substituted 1,4-dihydropyridines 15, 18 were also synthesized. Some of the obtained compounds were tested for their antimicrobial activity.

As a part of our programme aimed at developing efficient syntheses of polyfunctionally substituted azines and condensed azines, we have in the past reported efficient syntheses of compounds I-III. In conjunction of this work we report results of our further studies aimed at exploring the synthetic potentialities of I-III.

The ketoketene dimercaptal 1 prepared from 4-acetylbiphenyl and CS21) is a subject of current interest. The reaction of α-ketoketene-S,S-acetals and α-cyanoketene-S,S-acetals with guanidine and thiourea to give pyrimidine derivatives was reported2,3).