Structural studies on bioactive compounds. Part 27. Chemistry of the immunomodulatory agent bropirimine

Anticancer Drug Des. 1995 Apr;10(3):215-26.

Abstract

The 2-amino-6-phenylpyrimidin-4(3H)-ones bropirimine (1) and the debrominated analogue (4) undergo electrophilic nitration and sulphonation in the meta-position of the 6-phenyl group in strongly acidic conditions. Subsequent electrophilic substitutions take place in the 5-position of the pyrimidine ring, if vacant. Rearrangement of the 2-nitramino-6-phenyl-pyrimidines (22) and (23) furnishes the 2-amino-6-(3-nitrophenyl)pyrimidines (9) and (18), respectively. Nucleophilic substitutions, in contrast, occur readily in the pyrimidine 2-, 4- and 6-positions. Debromination of bropirimine by hydrazine hydrate can be rationalized by invoking an initial attack by the nucleophile at the electron-deficient pyrimidine 6-position. The reactive 4-chloro group in 5-bromo-4-chloro-2-formylamino-6-phenylpyrimidine (25) can be displaced with a range of nucleophiles (azide ion, ethanol, hydrazine, and primary and secondary aliphatic amines), without loss of the bromo substituent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / chemistry*
  • Cytosine / analogs & derivatives*
  • Cytosine / chemistry
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Molecular Structure
  • Spectrophotometry, Infrared

Substances

  • Adjuvants, Immunologic
  • Cytosine
  • bropirimine