Hydrolysis and subsequent cyclization of etazolate hydrochloride and related compounds in aqueous solutions: application of PMR and mass spectrometry in accelerated stability studies.
The hydrolysis of etazolate hydrochloride, an inhibitor of cyclic nucleotide 3',5'-monophosphate phosphodiesterase that degrades cyclic adenosine 3',5'-monophosphate (cyclic AMP) to adenosine 5'-monophosphate, and related compounds was studied by PMR and mass spectrometry. The compounds underwent reversible acid-catalyzed hydrolysis in aqueous solutions at 60 degrees, followed by cyclization to a major and a minor product formed by independent pathways. Under the experimental conditions, the minor product was stable. The formation rate of the major product, 6-ethyl-1,6-dihydrodipyrazolo [3,4-b:3',4'-d] pyridin-3(2H)-one, was considerably greater than that of the minor component, 3-ethoxy-6-ethyl-1,6-dihydrodipyrazolo [3,4-b:3',4'-d] pyridine. For the 6-methyl analog of etazolate, the rate of methyl deuteration was considerably slower than the rate of cyclization.
D003500:Cyclization; D004355:Drug Stability; D004974:Etazolate; D006868:Hydrolysis; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D010726:Phosphodiesterase Inhibitors; D012996:Solutions
D010726:Phosphodiesterase Inhibitors; D012996:Solutions; D004974:Etazolate