Novas pirimidinas: sÃntese e avaliaÃÃo de suas propiedades farmacolÃgicas

AUTOR(ES)
DATA DE PUBLICAÇÃO

2003

RESUMO

This work describes the synthesis of three series of compounds with pirimidinic ring and its pharmacological evaluations. First, the synthesis of compounds 4-amino-2,6-(diaryldissubistituted)- 5-carbonitrile-pyrimidines (5a-h) were achieved starting from arylamidine and bisnitriles. Second, the nitro-compounds (5k-o) have been reduced to their respective amines 4-amino-2-(arilsubstituted)-6-(p-amino)-5-carbonitrile-pyrimidines (6a-e). Condensation of amines with phthalic anhydride yielded the third series of compounds 4- amino-2-(p-arylsubstituted)-5-cyano-6-{4-(N-phthalimidophenyl)}-pyrimidines (7a-e). The molecular structures of these products were confirmed by usual methods, like proton nuclear magnetic resonance (1H-NMR), infrared spectroscopy (IR), mass spectrometry (MS) and elemental analyses. The compounds (5a-h) presented anti-inflammatory properties. The Dose/Response relationship of these drugs were made. The data obtained made possible the evaluation of the Quantitative Structure-Activity Relationships (QSAR). It was possible to synthesizes a new drug (5i) which is predicted to possess higher antiinflammatory activity. The theoretical model has been confirmed experimentally. Compounds 5b and 5h were evaluated for antitumoral activity in vivo using lapachol as the standard drug. The results show that the new compounds are active against two tumors, sarcoma-180 and the Erhlich carcinoma. Compound 5b showed better inhibitions (77,47 and 91,21%). cytotoxical assays were carried out using neoplasic cells (NCI-H292 and HEP2) to evaluate in vitro the activity of compounds 7a-e and 5c. The drugs demonstrated low cytotoxicity against the HEP2 cells. All the compounds were inactive over the NCIH292 cells

ASSUNTO(S)

Ãcidos nucleicos compostos pirimidÃnicos - sÃntese e avaliaÃÃo ciencias biologicas compostos pirimidÃnicos - heteroÃclos

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