W. Morozowich, T. Oesterling, W. L. Miller
Aug 1, 1979
Citations
0
Influential Citations
4
Citations
Quality indicators
Journal
Journal of Pharmaceutical Sciences
Abstract
Abstract Methods are described for the synthesis of dinoprost C 9 ‐ and C 15 ‐monoesters using protective groups. Esters at C 9 were synthesized by acylation of dinoprost 11,15‐bis(tetrahydropyran‐2‐yl)ether followed by acid‐catalyzed protective group removal. Esters at C 15 were synthesized by initial formation of the protected intermediate, dinoprost 9,11‐ n ‐butylboronate, followed by acylation and hydrolytic protective group removal. Many esters were active in vivo in the hamster antifertility screen. Plasma hydrolysis studies showed that the C 15 ‐esters were more readily cleaved than the C 9 ‐esters. In vivo studies in the rat showed that both the C 9 ‐ and C 15 ‐esters resulted in urinary excretion of 5α,7α‐dihydroxy‐11‐ketotetranorprosta‐l, 16‐dioic acid in amounts comparable to those obtained after dosing with dinoprost, indicating that ester hydrolysis occurred in vivo .