http://rdf.ncbi.nlm.nih.gov/pubchem/patent/GB-1041534-A
Outgoing Links
| Predicate | Object |
|---|---|
| assignee | http://rdf.ncbi.nlm.nih.gov/pubchem/patentassignee/MD5_d202e9e866984fe229f6facc38f1d740 |
| classificationCPCInventive | http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/C07J75-00 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/C07J21-00 |
| classificationIPCInventive | http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/C07J21-00 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/C07J75-00 |
| filingDate | 1963-04-24-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| inventor | http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_36dca5bcb7f274459842b05b8431cd1e http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_0612ec5247b27a650f588e8df5f6d1ec http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_ec677364830c4001419775c5097abe9d |
| publicationDate | 1966-09-07-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| publicationNumber | GB-1041534-A |
| titleOfInvention | 20-spiroxane compounds |
| abstract | The invention comprises steroids of the formulae <FORM:1041534/C2/10> wherein R1 is hydrogen or methyl; R2 is hydrogen, methyl or halogen; Y is hydrogen, keto or b -OH; R3 is hydrogen, C1- 8 alkanoylthio, mercapto, C1- 6 alkylthio, carboxy-C1- 6 alkylthio or a group -S-S-R5 in which R5 is a similar steroid nucleus; X is hydrogen or halogen but is hydrogen when Y is hydrogen; R4 is hydrogen, OH, C1- 8 alkanoyloxy, fluoro or methyl; R7 is hydrogen or C1- 6 alkyl; and R6 is C1- 6 alkyl, cyclohexyl or benzyl and the D 1 and D 6 double bonds are optional in the 3-keto compounds, and in the enol ethers the D 1 double bond is optional and there is a D 5 double bond when R1 is methyl and a D 5(10) double bond when R1 is hydrogen. They may be prepared as follows: 20-spirox-4-ene-3,21-dione is converted to its 3-ethylene ketal, this is reduced with lithium aluminium hydride in a solvent to 3 - ethylenedioxy - 17a - (31 - hydroxypropyl) -5-androsten-17b -ol, this is treated with an aryl sulphonyl halide and an organic base to give 3-ethylenedioxy-20-spirox-5-ene and this is hydrolysed to the D 4-3-one. Dehydrogenation with selenium dioxide gives the D 1,4-3-one or with chloranil in t-butanol gives the D 4,6-3-one which with selenium dioxide gives the D 1,4,6-3-one. The D 4,6-compound with a thioalkanoic acid gives the 7a -alkanoylthioD 4-3-one although the a -configuration is not definitely established. 20-Spirox-4-en-3-one with ethyl oxalate and methanolic sodium methoxide in t-butanol gives the sodium enolate of the 2-ethoxyoxalyl derivative which when methylated with methyl iodide in a solvent followed by treatment with sodium methoxide in the methanol gives 2a -methyl-20-spirox-4-en-3-one. Similar processes employing chlorine or FClO3 in place of the methylation step give the 2a -chloro and -fluoro compounds. These processes may also be effected with the 11b -hydroxy and D 9(11)-compounds and with compounds containing a 16-alkyl group. 20-Spirox-4,9(11)-dien-3-one with N-bromo-succinimide gives 9a -bromo-20-spirox-4-en-11b -ol-3-one, this on heating with potassium acetate in ethanol gives the 9b ,11b -epoxide, and this with HF in tetrahydrofuran gives the 9a -fluoro-11b -ol, which on oxidation gives the 11-one, as do other 11b -ols. 7a -Mercapto compounds are prepared by heating the 7a -alkanoylthio compounds with at least an equivalent of a strong base in an alkanol. Oxidation of the mercapto compounds by cold dilute hydrogen peroxide in an alcohol gives the corresponding disulphides. Reaction of the mercapto compounds with an alkanoyl halide gives the 7a -alkanoylthio derivatives while with a halogenoalkanoic acid in the presence of an acid acceptor the 7a -carboxyalkythio compounds are obtained and with an alkyl halide the 7a -alkylthio compounds result. 6-Hydroxy groups are introduced into the spiroxenones by treatment with orthoformic ester and dinitrobenzene-sulphonic acid to give a D 3,5-3-e-ol ether which with an organic peracid gives the required 6b -hydroxy compound. This may be acylated, the acylate epimerized by hydrogen chloride in chloroform to the 6a -alkanoyloxy compound and the latter hydrolysed to the 6a -hydroxy compound. A 6-fluoro or -methyl substituent is introduced by reaction of the D 5-ethyleneketol with perbenzoic acid to form the 5,6-epoxide and either reaction of this with boron trifluoride and acid hydrolysis and dehydration of the 5-hydroxy-6b -fluoro intermediate followed by epimerization with methanolic \sPOH to give the D 4-6a -fluoro compound or reaction with a methyl magnesium halide and similar hydrolysis dehydration and epimerization to give the D 4-6a -methyl compound. The 3-enol ethers are prepared from the D 3-3-ones and alkyl orthoformates or alkanols in iso-octane with p-toluene sulphonic acid, or by ether interchange. 19-Nor compounds are prepared by reacting 3-methoxy-17a -(31-hydroxypropyl) -1,3,5(10)-eetratrien-17b -ol or an 11-oxygenated derivative thereof with an organic sulphonyl halide in presence of an organic base to give a 3-methoxy-19-nor-20-spirox-1,3,5(10)-triene, reacting this with lithium in liquid ammonia to give a 3-methoxy-19-nor-20-spirox-2,5(10)-diene, treating this with an acidic reagent to give a 19-nor-20-spirox-5(10)-en-3-one and isomerizing this with a metal alkoxide in an alkanol. Substituents and double bonds may then be introduced by the methods described above.ALSO:Pharmaceutical compositions contain steroids of the formulae <FORM:1041534/A5-A6/1> (wherin R1 is hydrogen or methyl, R2 is hydrogen, methyl or halogen; Y is hydrogen, keto or B-hydroxy; R3 is hydrogen, C1-8 alkanoylthio, mercapto, C1-6 alkylthio, carboxy-C1-6 alkylthio, or a group -S-S-R5 in which R5 is a similar steroid nucleus; X is hydrogen or halogen, but is hydrogen when Y is hydrogen; R4 if hydrogen, OH, C1-8 alkanoyloxy, fluoro or methyl. R7 is hydrogen or C1-6 alkyl; and R6 is C1-6 alkyl, cyclohexyl or benzyl; and the D 1 and D 6 double bonds are optional in the 3-kato compounds, and in the enol ethers the D 1 double bond is optional and there is a D 5 double bond when R1 is methyl and a D 5(10) double bond when R1 is hydrogen), carriers and, optionally duiretics such as chlorothiazide and hydrochlorothiazide. The novel steroids are stated to block the salt-retaining effects of aldosterone and other salt-retaining steroids. |
| isCitedBy | http://rdf.ncbi.nlm.nih.gov/pubchem/patent/US-4559332-A http://rdf.ncbi.nlm.nih.gov/pubchem/patent/US-4309423-A http://rdf.ncbi.nlm.nih.gov/pubchem/patent/EP-0011818-A1 http://rdf.ncbi.nlm.nih.gov/pubchem/patent/US-3422096-A http://rdf.ncbi.nlm.nih.gov/pubchem/patent/US-4670551-A |
| priorityDate | 1963-04-24-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| type | http://data.epo.org/linked-data/def/patent/Publication |
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