CH531486A - Antiinflammatory pregnene-diones - Google Patents

Abstract

Trihydroxypregnene-3,20-diones (I) and especially 11 beta, 17 alpha, 21-trihydroxy-15, 16 beta-methylene-pregnene (4)-(and pregna-1,4-diene)-3,20-dione, for use as anti-inflammatories. R6 and R9 independently are H, halogen, R17, R21 independently are OH or O-acyl; Z is CO or beta-CH2OH. Preparation of (I) and 1,2-dehydro-deriv. by numerous methods e.g. (a) microbiological 11-hydroxylation of (I) (Z=CH2); (b) 1,2-dehydrogenation of a cmpd. (I); (c) adding HOCl or HOBr to the 9,11-double bond a cmpd. (I) or its, 1,2-dehydro-derivs. (Z = HC). In an example 11 beta, 17 alpha-21-trihydroxy-15,16 beta-methylene-pregnene (4)-3,20-dione, m.p. 219-221 degrees is obtained by microbiological hydroxylation of 17 alpha, 21-dihydroxy-15,16 beta-methylene-pregnene (4)-3,20-dione using Coniothyrium hellebori as organism.

Description

       

  
 



  Process for the production of new steroids of the Pregnan range
The invention relates to a process for the preparation of new steroids of the formula
EMI1.1
 in which X is bromine or chlorine, Rg is hydrogen, fluorine, chlorine or bromine, R17 and R21 are, independently of one another, hydroxy or acyloxy and Z is carbonyl or ß-hydroxymethylene.



   An acyloxy group preferably contains the residue of a saturated or unsaturated aliphatic or cycloaliphatic, an araliphatic or aromatic carboxylic acid having up to 20, preferably up to 12, carbon atoms. Examples of such acids are formic acid, acetic acid, pivalic acid, propionic acid, butyric acid, caproic acid, enanthic acid, oleic acid, palmitic acid, stearic acid, succinic acid, malonic acid, fumaric acid, citric acid, cyclohexylpropionic acid, phenylacetic acid and benzoic acid.



   A preferred group of compounds of the formula I are those in which R9 is hydrogen or fluorine, R17 and R21 are hydroxy or C 1 -C 4 alkanoyloxy and Z is β-hydroxymethylene.



   The inventive method is characterized in that a compound of the formula
EMI1.2
 in which X, Rg, R21 and Z have the meaning given above, dehydrohalogenated.



   The dehydrohalogenation according to the invention can be carried out using bases, e.g. B. organic bases such as pyridine can be accomplished.



   For the preparation of the starting materials for the process according to the invention, reference can be made to the Belgian patent specification No. 760392.



   The steroids of formula I are endocrine, especially anti-inflammatory. They can be used as a remedy e.g.



  in the form of pharmaceutical preparations which contain them in a mixture with a pharmaceutical, organic or inorganic inert carrier material suitable for enteral, percutaneous or parenteral administration. The pharmaceutical preparations can be in solid, semi-solid or liquid form. They may contain auxiliaries, such as preservatives, stabilizers, wetting agents or emulsifiers, salts to change the osmotic pressure or buffers. They can also contain other therapeutically valuable substances.

 

   example
500 mg 17.21 -diacetoxy-5a, 6ss-dichloro-1 lss-hydroxy-sabregan-3,20-dione were dissolved in 20 ml ethanol and refluxed with 1.0 g potassium acetate for one hour. The reaction product was poured into ice water and extracted with methylene chloride. The extract was washed with water, dried over Na2SO4 and evaporated. The residue was recrystallized from alcohol and pure 17,21-diacetoxy-6a-chloro-1 lss-hydroxy-pregn-4-en-3,20-dione was obtained.


    

Claims (1)

PATENT CLAIM Process for making new steroids of the formula EMI2.1 in which X is bromine or chlorine, R9 is hydrogen, fluorine, chlorine or bromine, R17 and R21 are independently hydroxy or acyloxy and Z is carbonyl or β-hydroxymethylene, characterized in that a compound of the formula EMI2.2 dehydrohalogenated. SUBClaim Process according to claim, characterized in that one starts from compounds of the formula II in which R9 is hydrogen or fluorine, R17 and R21 are hydroxy or C 1 -C alkanoyloxy and Z is β-hydroxymethylene.