GB1041534A - Creación de Inventos y Patentes con Inteligencia Artificial

GB1041534A – 20-spiroxane compounds
– Google Patents

GB1041534A – 20-spiroxane compounds
– Google Patents
20-spiroxane compounds

Info

Publication number
GB1041534A

GB1041534A
GB1616663A
GB1616663A
GB1041534A
GB 1041534 A
GB1041534 A
GB 1041534A
GB 1616663 A
GB1616663 A
GB 1616663A
GB 1616663 A
GB1616663 A
GB 1616663A
GB 1041534 A
GB1041534 A
GB 1041534A
Authority
GB
United Kingdom
Prior art keywords
hydrogen
methyl
gives
compounds
spirox
Prior art date
1963-04-24
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Expired

Application number
GB1616663A
Inventor
Glen Edward Arth
Harvey Schwam
Lewis Hastings Sarett
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Merck and Co Inc

Original Assignee
Merck and Co Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
1963-04-24
Filing date
1963-04-24
Publication date
1966-09-07

1963-04-24
Application filed by Merck and Co Inc
filed
Critical
Merck and Co Inc

1963-04-24
Priority to GB1616663A
priority
Critical
patent/GB1041534A/en

1966-09-07
Publication of GB1041534A
publication
Critical
patent/GB1041534A/en

Status
Expired
legal-status
Critical
Current

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Classifications

C—CHEMISTRY; METALLURGY

C07—ORGANIC CHEMISTRY

C07J—STEROIDS

C07J21/00—Normal steroids containing carbon, hydrogen, halogen or oxygen having an oxygen-containing hetero ring spiro-condensed with the cyclopenta(a)hydrophenanthrene skeleton

C—CHEMISTRY; METALLURGY

C07—ORGANIC CHEMISTRY

C07J—STEROIDS

C07J75/00—Processes for the preparation of steroids in general

Abstract

The invention comprises steroids of the formulae 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 (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.

GB1616663A
1963-04-24
1963-04-24
20-spiroxane compounds

Expired

GB1041534A
(en)

Priority Applications (1)

Application Number
Priority Date
Filing Date
Title

GB1616663A

GB1041534A
(en)

1963-04-24
1963-04-24
20-spiroxane compounds

Applications Claiming Priority (1)

Application Number
Priority Date
Filing Date
Title

GB1616663A

GB1041534A
(en)

1963-04-24
1963-04-24
20-spiroxane compounds

Publications (1)

Publication Number
Publication Date

GB1041534A
true

GB1041534A
(en)

1966-09-07

Family
ID=10072355
Family Applications (1)

Application Number
Title
Priority Date
Filing Date

GB1616663A
Expired

GB1041534A
(en)

1963-04-24
1963-04-24
20-spiroxane compounds

Country Status (1)

Country
Link

GB
(1)

GB1041534A
(en)

Cited By (5)

* Cited by examiner, † Cited by third party

Publication number
Priority date
Publication date
Assignee
Title

US3422096A
(en)

1967-08-08
1969-01-14
Searle & Co
Spiro(estrene/androstene-17,2′-oxetane)-3-one and intermediates

EP0011818A1
(en)

1978-11-22
1980-06-11
Ciba-Geigy Ag
Medicaments and pharmaceutical compositions based on aldosterone antagonists and diuretics and process for their manufacture

US4309423A
(en)

1977-05-31
1982-01-05
Ciba-Geigy Corporation
Compounds of the pregnane series with an oxygen function in the 19-position, processes for their manufacture and pharmaceutical preparations containing these compounds

US4559332A
(en)

1983-04-13
1985-12-17
Ciba Geigy Corporation
20-Spiroxanes and analogues having an open ring E, processes for their manufacture, and pharmaceutical preparations thereof

US4670551A
(en)

1984-06-21
1987-06-02
Ciba-Geigy Corporation
Epoxy steroids

1963

1963-04-24
GB
GB1616663A
patent/GB1041534A/en
not_active
Expired

Cited By (5)

* Cited by examiner, † Cited by third party

Publication number
Priority date
Publication date
Assignee
Title

US3422096A
(en)

1967-08-08
1969-01-14
Searle & Co
Spiro(estrene/androstene-17,2′-oxetane)-3-one and intermediates

US4309423A
(en)

EP0011818A1
(en)

1978-11-22
1980-06-11
Ciba-Geigy Ag
Medicaments and pharmaceutical compositions based on aldosterone antagonists and diuretics and process for their manufacture

US4559332A
(en)

1983-04-13
1985-12-17
Ciba Geigy Corporation
20-Spiroxanes and analogues having an open ring E, processes for their manufacture, and pharmaceutical preparations thereof

US4670551A
(en)

1984-06-21
1987-06-02
Ciba-Geigy Corporation
Epoxy steroids

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