GB929466A - Improvements in or relating to steroid derivatives - Google Patents

Abstract

The invention comprises P1p2-bis-steroid 21-pyrophosphates and salts thereof, the steroid being additionally characterized by a D 4- or D 1,4-double bond or bonds, 3- and 20-keto groups, an 11b -hydroxy or 11-keto groups and a 17a -hydroxy group; and their preparation by (1) de-aralkylation of an appropriate P1P2-bis-steroid diaralkyl pyrophosphate with an alkali metal halide in an organic solvent, to give a dialkali metal salt of the required pyrophosphate; or (2) condensing 2 molecules of a corresponding orthophosphate or a mono-sodium salt thereof in the presence of a carbodiimide R7N:C:NR8 (R7 and R8 being alkyl, cycloalkyl, aryl or aralkyl groups) or of cyanamide or a mono- or dialkylcyanamide. Suitable alkyl halides for use in process (1) are sodium iodide and lithium chloride, and the process may be combined with the preparation of the diaralkyl pyrophosphate starting material by condensing 2 molecules of a corresponding steroid 21-aralkyl hydrogen phosphate (obtained by acidification of a corresponding salt thereof) in the presence of one of the condensing agents referred to above or by condensing an appropriate 21-halogeno steroid with a P1P2 diaralkyl disilver pyrophosphate. The steroids of the invention may also contain 2- and/or 6-and/or 16-alkyl substituents, and/or 9-halo substituents, and/or a 6-fluoro substituent, and/or a 16-hydroxy or -acyloxy substituent, and they may form salts with, for example, alkali or alkaline earth metals, ammonia or organic bases such as N,N1-dibenzylethylene-diamine, the last named type of salts being prepared either from the free pyrophosphate and the free organic base or from an alkali metal or ammonium salt of the pyrophosphate and a salt of the base. Examples illustrate the compounds of the invention and their preparation by the above processes, and reference is also made to the conversion of corresponding pyrophosphates having a different steroid moiety, e.g. a saturated ring A, to the pyrophosphates of the invention, which have adrenocortical activity. The steroid pyrophosphates of the invention may be made up into pharmaceutical compositions with suitable carriers or diluents. These may take the form of solutions, tablets, capsules, syrups, elixirs, ointments, lotions, suppositories, or aerosols. In the Provisional Specification 21-pyrophosphates of steroids containing additionally or alternatively a saturated ring A, a D 5-double bond, no 11-substituent and no 17-substituent or a 17-acyloxy group are also referred to, and the pyrophosphate derived from pregnan-21-ol-3,20-dione and its alkali metal salts, which are intravenous anaesthetics, is stated to have improved solubility. De-aralkylation of diaralkyl steroid pyrophosphates by hydrogenolysis and treatment with anhydrous tertiary amines is also referred to. Specification 902,225 is referred to.