Utility of 6-amino-2-thiouracil as a precursor for the synthesis of bioactive pyrimidine derivatives

Bioorg Med Chem. 2007 Sep 15;15(18):6227-35. doi: 10.1016/j.bmc.2007.06.023. Epub 2007 Jun 14.

Abstract

The condensation of 6-amino-2-thiouracil 1 with aromatic aldehydes afforded azomethine derivatives 3a,b. The formed azomethines underwent [4+2] cycloaddition with enaminones 4a-c and enaminonitrile 9 to form the corresponding condensed pyrimidines 8a-f and 11a,b, respectively. On the other hand, the interaction of 3a,b with acetylene derivatives 12a,b, 14 afforded the corresponding pyrido[2,3-d]pyrimidines 13a-d and 16a,b, respectively. The newly synthesized 2-azadiene 18 reacted with ortho-aminophenol and ortho-aminothiophenol 19a,b to yield the amidines 21a,b. The in vitro antimicrobial activity of some of the newly synthesized compounds was examined. All the tested compounds proved to be active as antibacterial and antifungal agents. Also the in vivo antitumor activity of compounds 8a, 11b, 13a,d, and 16b against lung (H460) and liver (HEPG2) carcinoma cells was examined. Compounds 8a, 16b showed moderate activity against lung carcinoma cell line (H460).

MeSH terms

  • Antifungal Agents / chemical synthesis*
  • Antifungal Agents / chemistry
  • Antifungal Agents / pharmacology
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Drug Screening Assays, Antitumor
  • Gram-Negative Bacteria / drug effects*
  • Gram-Positive Bacteria / drug effects*
  • Humans
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / pathology
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Pyrimidines / chemical synthesis*
  • Pyrimidines / chemistry
  • Pyrimidines / pharmacology
  • Structure-Activity Relationship
  • Thiouracil / chemistry*
  • Tumor Cells, Cultured

Substances

  • Antifungal Agents
  • Antineoplastic Agents
  • Pyrimidines
  • Thiouracil
  • pyrimidine