Pyrazole derivatives. 5. Synthesis and antineoplastic activity of 3-(2-chloroethyl)-3,4-dihydro-4-oxopyrazolo[5,1-d]-1,2,3, 5-tetrazine-8-carboxamide and related compounds

J Med Chem. 1986 Aug;29(8):1544-7. doi: 10.1021/jm00158a041.

Abstract

Two pyrazolotetrazine derivatives were synthesized as the analogous prodrugs of the light-sensitive antineoplastic agents dacarbazine and BIC. Both the pyrazole derivatives are stable under ordinary light illumination. Biological evaluation of these pyrazoles revealed that the compound containing a 2-chloroethyl function (6a) demonstrated good antineoplastic activity in experimental animals, but the one containing a methyl function (6b) was inactive. The inactivity of compound 6b may suggest that compound 6a and related imidazotetrazines may simply act as biological alkylating agents per se rather than as prodrugs. The information could also imply that the postulated dealkylation mechanism for the triazene derivatives should be reexamined.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / therapeutic use
  • Colonic Neoplasms / drug therapy
  • Female
  • Leukemia L1210 / drug therapy
  • Mammary Neoplasms, Experimental / drug therapy
  • Mice
  • Pyrazoles / chemical synthesis*
  • Pyrazoles / therapeutic use
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Pyrazoles
  • 3-(2-chloroethyl)-3,4-dihydro-4-oxopyrazolo(5,1-d)-1,2,3,5-tetrazine-8-carboxamide