Phosphorus-nitrogen compounds. 20. Thiophosphorus hydrazones.

Six pyridine-2-carboxaldehyde, one pyridine N-oxide 2-carboxaldehyde, and five diketone thiophosphoric hydrazones, three thiophosphoric hydrazides, and two cupric chelates were synthesized. The chelates and nine of the hydrazones were tested against Ehrlich ascites carcinoma. Seven of these latter agents were administered concurrently with either cupric and/or ferrous salts to mice bearing this tumor. The greatest activity was found with the chelate, cimethyl pyridine-2-carboxyaldehyde phosphorothioic hydrazone-copper (1:1). The hydrazone portion of this chelate also formed a ligand-copper (2:1) complex. Although all of the hydrazones but one were inactive when evaluated alone, the concurrent injection of cupric ion increased survival times by an avoli alkaline phosphatase was found to be inhibited by two thiosemicarbazones in a manner similar to that previously reported by these agents against alkaline phosphatase derived from Sarcoma 180-6-thiopurine resistant ascites cells. None of the 14 hydrazides or hydrazones tested against E. coli enzyme displayed significant inhibition.