Prostaglandin prodrugs. 5.1 Prostaglandin E2 ethylene ketal.

Abstract

In order to improve the chemical stability of prostaglanding E2 (2), prostaglanding E2 ethylene ketal (1) was prepred by direct ketalization of 2 with ethylene glycol in benzene. To establish a quantitative assessment of 1 as a chemically stable and orally active prodrug of 2, the hydrolysis of 1 to 2 and the subsequent dehydration of 2 to prostaglandin A2 (3) were followed at 25 degrees C and six pH's ranging from 2.0 to 6.5 by means of a high-pressure liquid chromatographic procedure. Kinetic results clearly indicate that 1 should be quantitively hydrolyzed back to the parent drug 2 dehydration of 2 to 3 are in the order of 1 h and 14 days, respectively. The preliminary data on the biological response after oral administration of 1 appeared to indicate the 1 is bioequivalent to 2.

• Authors: M J Cho, G L Bundy, J J Biermacher
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 20 Issue 11 Pg. 1525-7 (Nov 1977) ISSN: 0022-2623 [Print] United States
• PMID: 410931 (Publication Type: Journal Article)

Chemical References

• Acetals
• Prostaglandins E, Synthetic

Topics

• Acetals (chemical synthesis)
• Animals
• Biological Availability
• Chemical Phenomena
• Chemistry
• Chromatography, High Pressure Liquid
• Drug Stability
• Female
• Haplorhini
• Hydrolysis
• Kinetics
• Macaca mulatta
• Pregnancy
• Prostaglandins E, Synthetic (chemical synthesis, pharmacology)
• Uterine Contraction (drug effects)