Quantitative structure-activity relationships of antitumor guanidinothiazolecarboxamides with survival enhancement for therapy in the 3LL Lewis lung carcinoma model

J Med Chem. 1991 Jul;34(7):1975-82. doi: 10.1021/jm00111a009.

Abstract

Guanidinothiazolecarboxamides (GTCs) are a novel class of antitumor agents found to be systemically active against experimental pulmonary metastases of 3LL Lewis lung carcinoma. A series of substituted benzothiazole GTCs were found to produce enhancement of survival in this model by using 8 days of intraperitoneal dosing initiated 2 days after intravenous tumor challenge. Quantitative structure-activity relationships have been discovered in the GTC series with survival enhancement correlated to substituent parameters. Optimal correlations were found between the probit transform of the drug-induced increased lifespan (ILS) and field and pi parameters. Among the most effective analogues in this series was N-(5-fluorobenzothiazol-2-yl)-2-guanidinothiazole-4-carboxam ide.

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / mortality
  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / therapeutic use
  • Chemical Phenomena
  • Chemistry
  • Female
  • Guanidines / chemical synthesis*
  • Guanidines / therapeutic use
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / mortality
  • Mice
  • Models, Biological
  • Neoplasms, Experimental / drug therapy
  • Neoplasms, Experimental / mortality
  • Structure-Activity Relationship
  • Thiazoles / chemical synthesis*
  • Thiazoles / therapeutic use

Substances

  • Antineoplastic Agents
  • Guanidines
  • Thiazoles
  • N-(5-fluorobenzothiazol-2-yl)-2-guanidinothiazole-4-carboxamide