Long-acting contraceptive agents: [formula omitted] hydrolysis of esters of norethisterone and levonorgestrel

• Published in: Steroids Vol. 41; no. 3; pp. 397 - 417
• Main Authors: Naderi, S., Fotherby, K.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 1983
• ISSN: 0039-128X; 1878-5867
• DOI: 10.1016/0039-128X(83)90110-1

The hydrolysis of 108 esters of norethisterone (17α-ethynyl-17β-hydroxyestr-4-en-3-one) was studied in vitro using a rabbit liver preparation. Introduction of a double or triple bond into a straight-chain ester did not inhibit hydrolysis but a marked reduction in hydrolysis was produced on replacement of a methylene group by an oxygen atom. Hydrolysis was inhibited by substituents at C2 of the ester chain except in short chain esters. Cyclopropylcarboxylate and cyclobutylcarboxylate were readily hydrolysed and introduction of a furan ring into the side-chain did not affect hydrolysis. No hydrolysis occurred with a cholesteryl carbonate ester or with a pentamethyldisilyloxy ether. Forty-nine esters of levonorgestrel (13β-ethyl-17α-ethynyl-17β-hydroxygon-4-en-3-one) were also studied. In general, the pattern of hydrolysis for these esters was similar to that of the norethisterone esters. However, with few exceptions the levonorgestrel esters were hydrolyzed more slowly. For those esters for which information regarding the biological activity was available, there was no correlation between the potency of the esters and their rate of hydrolysis in vitro .