http://rdf.ncbi.nlm.nih.gov/pubchem/patent/GB-902255-A
Outgoing Links
| Predicate | Object |
|---|---|
| assignee | http://rdf.ncbi.nlm.nih.gov/pubchem/patentassignee/MD5_232361c9031a709144573276863c462b |
| classificationCPCInventive | http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/C07J75-00 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/C07J5-00 |
| classificationIPCInventive | http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/C07J5-00 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/C07J75-00 |
| filingDate | 1957-11-19-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| inventor | http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_15e503498a75ed24844db1006ec81b96 http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_545750f6d9b4b0cda72cd74debc692ff |
| publicationDate | 1962-08-01-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| publicationNumber | GB-902255-A |
| titleOfInvention | Improvements in or relating to steroid derivatives |
| abstract | The invention comprises secondary phosphate esters of D 4-21-hydroxy-3:20-diketo-pregnenes which contain a b -hydroxy group or a ketonic oxygen atom in the 11-position and a hydroxy group in the 17a -position, and which may also contain an additional double bond in the 1-position, a halogen atom in the 19a -position and/or an alkyl group in the 16-position, the 21-ester group having the formula <FORM:0902255/IV (b)/1> (where R is alkyl or phenyl either of which may be substituted by a hydroxy, alkoxy, nitro, cyano, carboxy or carbalkoxy group or by a halogen atom; or a phenacyl or benzyl group either of which may be substituted by a nitro, cyano, carboxy or carbalkoxy group or by a halogen atom) and salts thereof with alkali metals or organic bases; and their preparation by removing the group Z from a corresponding steroid tertiary phosphate having in the 21-position the group <FORM:0902255/IV (b)/2> (where Z is a substituted or unsubstituted benzyl, phenacyl or electronegatively substituted phenyl group). When Z has one of the first three values it is removed by reaction with a halide salt in an organic solvent, but when it is a substituted phenyl group it is removed by hydrolysis e.g. with lithium hydroxide in aqueous dioxan. Examples are given. The phosphate ester starting materials are prepared (1) by reaction of the corresponding 21-halogeno or alkyl-, aralkyl- or aryl-sulphonyloxy streoids with a silver salt of the appropriate disubstituted phosphoric acid; or (2) by alkylation or aralkylation of the steroid secondary phosphate containing the group -O-PO.(OH)(OZ), in turn prepared from the corresponding dibenzyl or di(substituted benzyl) esters e.g. by treatment with sodium iodide in acetone; or (3) by reacting the di-silver salt of the steroid primary phosphate (prepared from the disodium salt and, for example, silver nitrate) with a compound RX (X is a halogen), when R is to be the same as Z; or (4) by the method described in Specification 902,254. Silver benzyl o-methoxyphenylphosphate is prepared by reacting dibenzylphosphochloridate with potassium o-methoxyphenate to give dibenzyl o-methoxyphenylphosphate, heating this with sodium iodide in acetone to give sodium benzyl o-methoxyphenylphosphate and reacting this with silver nitrate. The corresponding p-methoxy compounds are prepared similarly. Silver benzyl p-nitrophenylphosphate is prepared by treating benzyl di-(p-nitrophenyl)phosphate with lithium hydroxide, and treating the product with hydrogen ions and then silver nitrate. Silver di-p-cyanobenzyl-phosphate is prepared by reacting p-cyanobenzyl bromide with trisilver phosphate to give tri-p-cyanobenzylphosphate, boiling this with sodium iodide in acetonitrile to give di-p-cyanobenzyl hydrogen phosphate, and reacting this with silver nitrate. Silver benzyl o-carbo-methoxyphenyl phosphate is prepared by reacting dibenzyl phosphite with sulphuryl chloride and then methyl salicylate to give o - carbomethoxyphenyl dibenzylphosphate, heating this with sodium iodide in acetone to give sodium benzyl o-carbomethoxyphenyl phosphate, and treating this with hydrogen ions and then silver carbonate. The phosphate esters, which are stated to have particularly prolonged adrenocortical action, may be formulated as pharmaceutical compositions for injection or oral or topical application, for example as aqueous solutions, tablets, capsules or ointments. The Provisional Specification refers to secondary 21-phosphates of 20-keto-steroids of the pregnane and allopregnane series in general, and refers specifically to steroids of the formula <FORM:0902255/IV (b)/3> wherein R is an alkyl, hydroxyalkyl, aryl or aralkyl group, R1 and R2 are hydrogen atoms or methyl groups, R3 is hydrogen or a halogen atom, R4 and R5 are hydrogen or hydroxy or acyloxy groups, X is hydroxy or ketonic oxygen and Y is hydroxy, acyloxy or ketonic oxygen, and the corresponding D 1, D 4 and D 1,4 compounds, and their salts. It also refers to removal of the group Z by methods such as hydrogenolysis and treatment with anhydrous tertiary amines. |
| priorityDate | 1957-11-19-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| type | http://data.epo.org/linked-data/def/patent/Publication |
Incoming Links
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