Antimicrobial and antitumor activity of N-heteroimmine-1,2,3-dithiazoles and their transformation in triazolo-, imidazo-, and pyrazolopirimidines

Bioorg Med Chem. 2002 Feb;10(2):449-56. doi: 10.1016/s0968-0896(01)00294-2.

Abstract

The reaction of Appel's salt with o-amino nitrile heterocycles 10-19 gave the corresponding 4-chloro-5-heteroimmine-1,2,3-dithiazoles 20-29 which were evaluated for their antibacterial, antifungal and antitumor activity. Although all these N-heteroimines were devoid of significant antibacterial activity, they showed significant antifungal activity. Moreover, the same derivatives represent highly versatile intermediates in heterocyclic synthesis, in fact the pyrazoleimino dithiazoles 20-26 can be converted in one step into 2-cyano derivatives of the corresponding 4-methoxy-pyrazolo[3,4-d]pyrimidines 30-35 by sodium methoxide in refluxing methanol. This provides a general and attractive route to 4-methoxy-6-cyano pyrazolo[3,4-d]pyrimidines from 1-substituted 5-amino pyrazoles 10-19 in two simple steps. Finally, the isosteric replacement of the pyrazole ring atoms to give the imidazole[3,4-d]pyrimidine and triazole [4,5-d] pyrimidine ring systems was examined.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents
  • Anti-Infective Agents / chemistry*
  • Anti-Infective Agents / pharmacology*
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Candida / drug effects
  • Drug Screening Assays, Antitumor
  • Gram-Negative Bacteria / drug effects
  • Humans
  • Inhibitory Concentration 50
  • Mice
  • Microbial Sensitivity Tests
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • Anti-Bacterial Agents
  • Anti-Infective Agents
  • Antineoplastic Agents