Isolation and identification of impurities in 4-acetyl-2-(2'-hydroxyethyl)5,6-bis(4-chlorophenyl)-2H-pyridazin-3-one, an antihypertensive agent.
Three trace impurities found in 4-acetyl-2-(2'-hydroxyethyl)-5,6-bis(4-chlorophenyl)-2H-pyridazin-3-one (II), a novel antihypertensive agent, were isolated by a combination of low-pressure liquid chromatography and preparative TLC. These impurities were identified as the formate ester of II, a pyridazinone having a 2-methyl rather than the 2'-hydroxyethyl substituent, and a bis(pyridazinonyl)methane analog. In addition, the product of O-alkylation rather than of N-alkylation of 4-acetyl-5,6-bis(4-chlorophenyl)-2H-pyridazin-3-one (I) with ethylene carbonate was detected by high-performance liquid chromatography. The biological activity of these four impurities was compared to that of II.
D000818:Animals; D000959:Antihypertensive Agents / Q000032:analysis* / Q000633:toxicity; D001794:Blood Pressure / Q000187:drug effects; D004340:Drug Contamination; D007928:Lethal Dose 50; D011724:Pyridazines / Q000302:isolation & purification* / Q000494:pharmacology / Q000633:toxicity; D051381:Rats
D000959:Antihypertensive Agents; D011724:Pyridazines; C030219:4-acetyl-2-(2'-hydroxyethyl)-5,6-bis(4-chlorophenyl)-2H-pyridazin-3-one