Patent GB-843820-A (GB)
Title: Improvements in and relating to andrenocorticotropic action-retarding and anti-enzymatic aromatic polyphosphates
IPC: C07F9/12
Filed: 1957-01-02
Abstract: New aqueous alkali soluble aromatic polyphosphates of molecular weight above 2000, which are adrenocorticatropic action retarding and anti-enzymatic substances, have the formula:  <FORM:0843820/IV(a)/1> in which n is an integer and R represents a binuclear aromatic group of formula:  <FORM:0843820/IV(a)/2> wherein R1 and R2 are hydrogen or methyl, and X is a bivalent aliphatic hydrocarbon radical comprising 1 to 3 carbon atoms in a straight chain between the two nuclei, the said carbon atoms carrying hydrogen atoms and/or alkyl, alkenyl or alkylidene groups of not more than 4 carbon atoms, with the proviso that if R1 and R2 are both hydrogen, these groups may not be methyl if X is methylene, or hydrogen or ethylidene if X is ethylene.  These polyphosphates are made by reacting a phosphorylating agent (e.g. phosphorous oxychloride or oxybromide) with a dihydric phenol of formula <FORM:0843820/IV(a)/3> preferably in the presence of a tertiary amine as a hydrogen halide binding agent, followed by hydrolysis of the product. Preferably phosphorylation is effected by adding 0.7-1.0 mols. of the phosphorylating agent to 1 mol of the dihydric phenol dissolved in a solvent and cooling to regulate the process. Specified dihydric phenols are 4.41-dihydroxy-3-methyldiphenylmethane, bis - (p - hydroxyphenyl) - isopropylmethane, bis-(p-hydroxyphenyl) - ethylidenemethane, bis - (4 - hydroxy-3-methylphenyl)-ethyl-n-propylmethane, 4,41-dihydroxy - a ,b - diethylstilbene, 4,41 - di - hydroxy-a -isopropyl - stilbene, 4.41-dihydroxy-a -methyl-b -n-propylstilbene, 4.41-dihydroxy a -methyl-b -propienystilbene, 4.41-dihydroxy-a -2-dimethyl-b -ethylstilbene, 4.41-dihydroxy-a  b  2-21-tetramethylstilbene, 4-41-dihydroxy a -b -3,3-tetramethyl stilbene, 4,41-dihydroxy-diphenyl-a ,a -dimethylethane, 4,41-dihydroxy-2-methyldiphenyla  -methylethane, 4,41-dihydroxya ,b  - bis - n - propyldiphenylethane, 4,41-dihydroxy-a -2-dimethyl-b -ethyl diphenylethane, 4,41- dihydroxya ,b -diethylg -methyl-biphenyl propane, 3,4-bis (p. hydroxyphenyl)-hexane and 4,1-dihydroxy-3,31-dimethyl-g d -diphenyl-b  d  -hexadiene.  Examples are given.  Specification 753,319 is referred to.ALSO:In order to increase the hormonal effect of adrenocorticotropic hormone (ACTH) when injected intramuscularly, it is used in admixture with a certain aqueous alkali soluble aromatic polyphosphate of molecular weight exceeding 2000 which is an adrenocorticotropric action-retarding and an anti-enzymetic substance.  The polyphosphate has the formula: <FORM:0843820/VI/1> where n is an integer and R is a binuclear aromatic group of the formular:  <FORM:0843820/VI/2> wherein R1 and R2 are hydrogen or methyl and X is a bivalent aliphatic hydrocarbon radical comprising 1-3 carbon atoms in a straight chain between the two nuclei, the said carbon atoms carrying hydrogen atoms and/or alkyl, alkenyl or alkylidene groups of not more than 4 carbon atoms, with the proviso that if R1 and R2 are both hydrogen, these groups may not be methyl if X is methylene, or hydrogen or ethylidene if X is ethylene; the said polyphosphate having one or more hydroxyl groups or salt groups attached to phosphorous.  Specification 753,319 is referred to.