Enaminones as Building Blocks for the Synthesis of Substituted Pyrazoles with Antitumor and Antimicrobial Activities.docVIP

Molecules 2011, 16, 1834-1853; doi:10.3390/moleculeOPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Article Enaminones as Building Blocks for the Synthesis of Substituted Pyrazoles with Antitumor and Antimicrobial Activities Sayed M. Riyadh Department of Chemistry, Faculty of Science, University of Cairo, Giza, 12613, Egypt; E-Mail: riyadh1993@ Received: 12 February 2011 / Accepted: 17 February 2011 / Published: 22 February 2011 Abstract: Novel N-arylpyrazole-containing enaminones 2a,b were synthesized as key intermediates. Reactions of 2a,b with active methylene compounds in acetic acid in the presence of ammonium acetate afforded substituted pyridine derivatives 5a-d. Enaminones 2a,b also reacted with aliphatic amines such as hydrazine hydrate and hydroxylamine hydrochloride to give bipyrazoles 8a,b and pyrazolylisoxazoles 9a,b, respectively. On the other hand, treatment of 2a,b with a heterocyclic amine and its diazonium salt yielded the respective [1,2,4]triazolo[4,3-a]pyrimidines 12a,b and pyrazolylcarbonyl[1,2,4]triazolo- [3,4-c][1,2,4]triazines 14a,b. Moreover, 2-thioxo-2,3-dihydro-1H-pyrido[2,3-d]pyrimidin- 4-one (17) was prepared via reaction of enaminone 2a with aminothiouracil (15). Cyclocondensation of 17 with the appropriate hydrazonoyl chlorides 18a-c gave the corresponding pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidin-5-ones 21a-c. The cytotoxic effects of compounds 2b, 14a and 17 against human breast cell line (MCF-7) and liver carcinoma cell line (HEPG2) were screened and in both lines they showed inhibition effects comparable to those of 5-fluorouracil, used as a standard. The antimicrobial activity of some products chosen as representative examples was also evaluated. Keywords: (dimethylamino)acryloylpyrazole; hydrazonoyl chlorides; antitumor activity; antimicrobial activity 1. Introduction The growing interest in bioactive N-ary