Steroid-Verbindungen

摘要

Novel steroids of the formulae (wherein R1 is hydrogen, acyl, alkyl, aralkyl, cycloalkyl, aryl, aromatic heterocyclic, o-, m-, or p-halophenyl, o, m-, or p-methylphenyl, o-, m-, or p-alkoxyphenyl, o-, m-, or p-nitrophenyl, b -hydroxyethyl or phenethyl; R2 is hydrogen, fluorine, chlorine or methyl; and R3 is hydrogen, chlorine, fluorine, hydroxy, acyloxy or dihydrogen phosphate or alkali metal salt thereof) and their D 4'6-analogues, and their 16,17-acetals and ketals with aldehydes and ketones L.CO.M in which L and M are hydrogen, alkyl or aryl or are joined in an alkylene chain; are prepared (1) by treating the appropriate 2-hydroxy- or -acyloxy-methylene - 3 - keto - 16a ,17a ,21 - trihydroxy - 20 - ethylenedioxy - D 4 - pregnenes or - D 4'6 - pregnadienes with the appropriate hydrazine and hydrolysing off the ketal group in the products with sulphuric acid; or (2) treating the appropriate 2 - hydroxy- or - acyloxy - methylene - 3 - keto - 16a ,17a - hydrocarbondioxy - 20 - keto - 21 - tetrahydropyranyloxy - D 4 - pregnenes or D 4'6 - pregnadienes with the appropriate hydrazine, and hydrolysing off the 21-ether group in the products with a strong acid. The 16a ,17a -diols and their acetals and ketals may be interconverted by standard procedures. The nature of thepyrazolo products when R1 is not hydrogen, i.e. whether they are 11- or 21-isomers, depends on the nature of the hydrazine and on whether a 2-hydroxymethylene or 2-alkoxymethylene starting material is used. The isomers may be separated by chromatography. The N-alkyl-[3,2-c]pyrazoles may also be prepared by direct alkylation of the N-unsubstituted compounds. N-acyl compounds are prepared by conversion to 21-tetrahydropyramyl ethers, N-acylation, and removal of the ether group. Acylation of N-unsubstituted 21-diols gives N,21-diacylates, from which the N-acyl group may be preferentially hydrolysed. 21-Unsubstituted compounds are prepared by standard methods via the 21-mesylates and 21-iodo compounds, N-unsubstituted compounds being protected by conversion to the N-carbamoyl derivatives. 21-Fluoro and -chloro compounds are prepared from the 21-mesylates and alkali metal fluorides or lithium chloride. 21-Phosphate esters and their salts are prepared from the 21-iodo compounds by standard methods. Starting materials are prepared by methods illustrated in the following reaction sequences The [3,2-c]pyrazolo-steroids of the invention which are stated to have anti-inflammatory activity, may be made up into pharmaceutical compositions for topical use with suitable carriers.