2,3,5,6-Tetrachloro-4-pyridinol: A New Chemical Structure for Anticoagulant Activity

Summary

The LD₅₀ and 95% confidence interval for the sodium salt of 2,3,5, 6-tetrachloropyridinol (TCP) was found to be 155 (130-184) mg/kg at 72 hr following intragastric administration to male mice. Similarly, the LD₅₀ and 95% confidence interval for female mice was found to be 190 (168-215) mg/kg.

The effect of three doses of intragastrically administered TCP was studied in rats. Statistical analysis of the data indicated that a significant increase in 1-stage prothrombin time could be found at 24 hr post drug administration. No difference in the magnitude of effect could be demonstrated for animals treated with 76.6, 60.2, and 43.8 mg/kg of TCP after this amount of time. The peak effect of the compound was found to occur at approximately 48 hr post drug when a significant regression of prothrombin time on log dose could be demonstrated. Evidence for lowered prothrombin activity could be found at 96 hr but not at 144 hr post-TCP administration. The activity of eight structural analogs of TCP is discussed.