Steroids XLIV. Synthesis and D-homoisomerization of 3β-acetoxy-6α-(N-acetylanilino)-17α-hydroxypregn-5-en-20-one
Summary1.The reactions of 16β-bromo-3β,17α-dihydroxypregn-5-en-20-dione (III) and its 3,17-diacetate (IV) with aniline have been studied. The reaction of (III) with aniline leads to the formation of the 20-anil of 16α,17α-epoxypregnenolone (V) and the reaction of (IV) with aniline to the formation of 3-acetoxy-16α-(N-acetylanilino)-17α-hydroxypregn-5-en-20-one (IX).2.The hydrolysis of the diacetate (IX) with potassium carbonate in aqueous methanol has been studied. The hydrolysis is accompanied by D-homoisomerization with the formation of 16α-anilino-3β,17α-dihydroxy-17β-methyl-D-homoandrost-5-en-17a-one.3.The structures and configurations of the compounds obtained (V, VI, VII, IX, X, and XI) have been shown by a series of chemical transformations and by physicochemical methods.
Mass spectrometry of steroid systems.—XX The application of the ionization efficiency curves to some stereochemical problems†
The dependence of the cleavage of some cis/trans-isomers in the terpenoid and steroid series on the energy of the ionizing electrons have been studied.
Multiple-dose pharmacokinetics of moxisylyte after oral administration to healthy volunteers.
The pharmacokinetics of moxisylyte in plasma and urine was investigated after oral administration. Twelve subjects were treated orally, twice daily with 240 mg of the drug for 6 days; on day 7, the subjects received a last dose of 240 mg of moxisylyte. Moxisylyte was assayed in plasma and urine by a specific HPLC method with fluorimetric detection. Moxisylyte was absorbed rapidly and changed to its metabolites immediately after drug administration; unchanged moxisylyte was not found in plasma. Two metabolites were found in plasma and urine: conjugated desacetylmoxisylyte (DAM) and the conjugate of desmethylated DAM (MDAM). The pharmacokinetic parameters determined after the first oral administration were not modified on multiple dosing. The apparent elimination half-lives of conjugated DAM and MDAM were 2.3 and 3.5 h, respectively. Elimination of these two metabolites in urine averaged 50 and 10%, respectively.