GB1478968A - Alkylated pregnanes - Google Patents

Alkylated pregnanes

Info

Publication number
GB1478968A
GB1478968A GB33149/73A GB3314973A GB1478968A GB 1478968 A GB1478968 A GB 1478968A GB 33149/73 A GB33149/73 A GB 33149/73A GB 3314973 A GB3314973 A GB 3314973A GB 1478968 A GB1478968 A GB 1478968A
Authority
GB
United Kingdom
Prior art keywords
methyl
dione
hydroxy
pregnen
pregnadiene
Prior art date
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
GB33149/73A
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.)
Akzo NV
Original Assignee
Akzo NV
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.)
Filing date
Publication date
Application filed by Akzo NV filed Critical Akzo NV
Priority to GB33149/73A priority Critical patent/GB1478968A/en
Priority to IE1428/74A priority patent/IE39593B1/en
Priority to ZA00744381A priority patent/ZA744381B/en
Priority to FI742103A priority patent/FI52100C/en
Priority to AU71040/74A priority patent/AU487996B2/en
Priority to SE7409046A priority patent/SE402920B/en
Priority to DE2433178A priority patent/DE2433178A1/en
Priority to JP49079023A priority patent/JPS5047968A/ja
Priority to CA204,503A priority patent/CA1050529A/en
Priority to DK371174AA priority patent/DK134700B/en
Priority to NL7409298A priority patent/NL7409298A/en
Priority to ES428132A priority patent/ES428132A1/en
Priority to BE146467A priority patent/BE817543A/en
Priority to HU74AO00000386A priority patent/HU171711B/en
Priority to FR7424189A priority patent/FR2236508B1/fr
Priority to US05/663,893 priority patent/US4031075A/en
Publication of GB1478968A publication Critical patent/GB1478968A/en
Expired legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J9/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Steroid Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)

Abstract

1478968 21-Alkylated-pregnanes AKZO NV 10 July 1974 [11 July 1973] 33149/73 Heading C2U Novel steroids have the formula wherein X is H, F or Cl; Y is H 2 , H(OH), H(O acyl), =0, H(F) except when X is F, or H(C1); R 1 is C 1-4 alkyl; R 2 is H or C 1-4 alkyl; R 3 is H, CH 3 or halogen; Z is OH, O alkyl or O acyl or forms together with R 4 a group as indicated hereinafter; Q is, when #<SP>15</SP> is absent, C 1-4 alkylidene or (#-H) (α-R 4 ) in which R 4 is, together with Z, C 3-5 alkylidenedioxy, C 1-4 alkylidene, C 7-8 aralkylidene, alkylone of the formula in which A is H or halogen and B is H, halogen, C 1-4 alkyl, haloalkyl, alkoxy or phenyl, or a [17α,16α-d]- or [16α,17α-d]-oxazolino group wherein the 2<SP>1</SP>-position may be C 1-4 alkyl- or phenyl-substituted, or Q (when A<SP>15</SP> is present) is CH 3 or halomethyl; and #<SP>1</SP>- and #<SP>6</SP>-double bonds are optionally present. They are prepared from corresponding #<SP>16</SP>-steroids by introducing the required substituents into the D ring or from corresponding steroids containing -COCH 2 R 5 (wherein R 5 is H or halogen) in place of -COCHR 1 R 2 by mono- or di-alkylation. In representative examples (i) 3#-hydroxy- #<SP>9(11),16</SP> - 5α - pregnadien - 20 - one 3 - tetrahydropyranyl ether (from the free 3-ol) is 21- methylated with 3-hydrolysis, the 3#-hydroxy- 21 - methyl - #<SP>9(11),16</SP> - 5α- pregnadien - 20 - one is epoxidized, the 3#-hydroxy-16α,17α-epoxy-21- methyl - #<SP>9(11)</SP> -5α pregnen - 20 - one is converted to 3#,16α,17α - trihydroxy - 21 - methyl- #<SP>9(11)</SP>- 5α-pregnen - 20 - one 16 - acetate 20 - carbethoxyhydrazone, this is converted to 3#,16α,17α - trihydroxy - 21 - methyl - #<SP>9(11)</SP> 5α - pregnen - 20 - one 16 - acetate, this to 3# - hydroxy - 16α,17α - isopropylidenedioxy- 21 - methyl - #<SP>9(11)</SP>5α - pregnen - 20 - one, this to the corresponding 3,20-dione, this to the corresponding #<SP>1</SP>'<SP>4,9(11)</SP> -pregnatriene, this to 9α - bromo - 11# - hydroxy - 16α,17α - isoprpylidenedioxy - 21 - methyl - #<SP>1,4</SP>-pregnadiene- 3,20-dione and this to 11#-hydroxy-16α,17α- isopropylidenedioxy -21 - methyl - #<SP>1</SP>'<SP>4</SP>- pregnadiene - 3,20 - dione; (ii) 3# - hydroxy- 16α,17α - epoxy - 21 - methyl - #<SP>9(11)</SP>5α- pregnen - 20 - one is converted via 3#,17α-dihydroxy - 16# - azido - 21 - methyl - #<SP>9(11)</SP>- 5α - pregnen - 20 - one, 3,17 - diacetate, the corresponding 16#-amino, 16#-chloramino and 16 - imino compounds, 3#,17α - dihydroxy- 16 - acetamido - 21 - methyl - #<SP>9(11),15</SP> - pregnadien - 20 - one diacetate, the corresponding free diol, the 3-monoacetate, 3#,17α-dihydroxy- 16α - acetamido - 21 - methyl - #<SP>9(11)</SP>5α- prenen - 20 - one 3 - acetate, the corresponding free diol, the corresponding 3,20-dione, [16α, 17α-d] - 2<SP>1</SP>- methyl - oxazoline - 21 - methyl- #<SP>9(11)</SP>5α- pregnene - 3,30 - dione, a crude 2,4 - di bromo derivative, [16α,17α-d] - 2<SP>1</SP>- methyl - oxazoline - 21 - methyl - #<SP>1,4,9(11)</SP> pregnatriene - 3,20 - dione, and the corresponding 9α - bromo - 11#-hydroxy - #<SP>1,4</SP>- pregnadiene to 11#- hydroxy - [16α,17α,-d]- 21 - methyloxazoline - 21 - methyl - #<SP>1,4</SP>- pregnadiene - 3,20 - dione; (iii) 3#,11#- diacetoxy - 21 - methyl - #<SP>16</SP> - 5α - pregnen - 20- one is converted via 3#,11# - diacetoxy- 16,21 - dimethyl - #<SP>16</SP> - 5α- pregnen - 20 - one, 3#,11# - dihydroxy - 16#,21 - dimethyl - 16α,17α- epoxy - 5α - pregnan - 20 - one 11# - acetate (compound A), 3#,11#,17α - trihydroxy - 16- methylene - 21 - methyl - 5α - pregnan - 20- one 11#- acetate and the corresponding #<SP>1,4</SP>-3,20 - dione into 11#-17α, - dihydroxy- 16 - methylene - 21 - methyl - #<SP>1,4</SP>-pregnadiene- 3,20 - dione; (iv) 3#,11#- dihydroxy - #<SP>16</SP>- 5α - pregnen - 20 - one is converted via its 3,11 - ditetrahydropyranyl ether, 3#,11#- dihydroxy - 21 - methyl - #<SP>16</SP> - 5α - pregnen- 20 - one, its diacetate, 3#,11#,16# - trihydroxy- 17α - bromo - 21 - methyl - 5α - pregnan - 20- one 3,11 - diacetate 16 - formate, 3#,11#- dihydroxy - 16#,17# - epoxy - 21 - methyl- 5α - isopregnan - 20 - one 11 - acetate, 3#,11#,- 16α - trihydroxy - 17α - azido - 21 - methyl - 5α- pregnan - 20 - one 11 - acetate, the corresponding triacetate, the corresponding 17α-amino compound, 3#,11# - dihydroxy - [17α,16α-d]- 2<SP>1</SP> - methyloxazoline - 21 - methyl - 5α - pregnan- 20 - one 3,11 - diacetate, the corresponding 11 - monoacetate, the corresponding 3,20- dione and the corresponding #<SP>1,4</SP>-compound to 11# - hydroxy[17α,16α-d] - 2<SP>1</SP> - methyloxazoline 21 - methyl - #<SP>1,4</SP> - pregnadiene - 3,20 - dione; (v) 3# - hydroxy - [17α,16α-d] - 2<SP>1</SP> - methyloxazoline - #<SP>9(11)</SP> - 5α - pregnen - 20 - one is converted via the corresponding 3-thp-ether, 3#- hydroxy - [17α,16α,-d] - 2<SP>1</SP> - methyloxazoline- 21 - methyl - #<SP>9(11)</SP> - 5α - pregnen - 20 - one and the corresponding 3,20-dione to [17α, 16α,-d]-2<SP>1</SP>- methyloxazoline - 21 - methyl - #<SP>1</SP>'<SP>4,9(11)</SP>- pregnatriene - 3,20-dione; (vi) compound A (see (iii)) is converted via 3#,11#,17α,-trihydroxy- 16,21 - dimethyl - #<SP>15</SP> - 5α - pregnen - 20 - one 11# - acetate, the corresponding 3-ones, and 11#,17α, - dihydroxy - 16,21 - dimethyl - #<SP>1,4,15</SP>- pregnatriene - 3,20 - dione 11# - acetate into 11#,17α - dihydroxy - 16,21 - dimethyl - #<SP>1,4,15</SP> - pregnatriene - 3,20 - dione; (viii) 3# - hydroxy- #<SP>9(11)</SP>,<SP>16</SP> - 5α , pregnadien - 20 - one acetate is converted via a crude pyrazoline, 3#-hydroxy- 16α,17α - methylene - #<SP>9(11) </SP>- 5α - pregnen - 20- one acetate, the corresponding free 3 - ol, its 3,3-dimethyl ketal and 16α,17α-methylene-21- methyl - #<SP>9(11)</SP> - 5α - pregene - 3,20 - dione to 11# - hydroxy - 16α,17α - methylene - 21- methyl - #<SP>1,4</SP> - pregnadiene - 3,20 - dione; (viii) 16α,17α - isopropylidenedioxy - 21 - methyl - #<SP>9(11)</SP> - 5α - pregnene - 3,20 - dione is converted via a crude 2α-bromo derivative, the corresponding #<SP>1,9(11)</SP> - pregnadiene, and 16α,- 17α, - isopropylidenedioxy - 21 - methyl- #<SP>1,4,9(11)</SP> - pregnatriene - 3,20 - dione (which may also be prepared via a dibromo derivative of the starting material) to 9α-fluoro-11#- hydroxy - 16α,17α - isopropylidenedioxy - 21- methyl - #<SP>1,4</SP> - pregnadiene - 3,20 - dione; (ix) 3#,11# - diacetoxy - 21 - methyl - #<SP>16</SP> - 5α- pregnen - 20 - one is converted via 3#,11#- diacetoxy-16α,17α - ethylene - 21 - methyl- 5α - pregnan - 20 - one, the corresponding 11- monoacetate, the corresponding 3,20-dione and the corresponding #<SP>1</SP>'<SP>4</SP>- compound to 11#- hydroxy - 16α,17α - ethylene - 21 - methyl- #<SP>1,4</SP> - pregnadiene - 3,20 - dione; (x) and (xi) various 11#-ols of the invention are converted via the corresponding #<SP>9(11)</SP>-compounds, 9α- bromo - 11#-ols and 9#,11# - epoxides into 9α-fluoro-11#-ols, and there are oxidized to the corresponding 11-ones; (xii), (Xiii) and (xiv) 9α,11# - dichloro-16α,17α - isopropylidenedioxy- 21 - methyl - #<SP>1,4</SP> - pregnadiene - 3,20 - dione is prepared from the corresponding #<SP>1,4,9(11)</SP> - compound and other inventive compounds are prepared similarly, as are 9α - chloro- 11#- hydroxy - 16α,17α - methylene - 21- methyl - #<SP>1,4</SP> - pregnadiene - 3,20 - dione and 9α - chloro - 11# - fluoro - [16α,17α-d] - 2<SP>1</SP> - methyloxazoline - 21 - methyl - #<SP>1,4</SP> - pregnadiene - 3,20 - dione; (xv) 11# - hydroxy- 16α,17α - isopropylidenedioxy - 21 - methyl- #<SP>1,4,</SP>6 - pregnatriene - 3,20 - dione 11 - acetate is prepared from the corresponding #<SP>1,4</SP>- pregnadiene; and (xvi) 3# - hydroxy - 21- methyl - #<SP>5,16</SP>pregnadien - 20 - one is converted via 3# - hydroxy - 16α,17α - isopropylidenedioxy - 21 - methyl - #<SP>5</SP>- pregnen - 20 - one, 3#- acetoxy - 5α,6α - epoxy - 16α,17α - ipdo- 21 - methyl - 5α - pregnan - 20 - one, the corresponding 5α - hydroxy - 6# - fluoro compound, the corresponding 3#-ol and 3-one and 6α - fluoro - 16α,17α-ipdo - 21 - methyl - #<SP>4</SP>- pregnene - 3,20 - dione to 6α - fluoro - 16α,17α- isopropylidenedioxy - 21 - methyl - #<SP>1,4</SP> pregnadiene-3,20-dione. Corresponding reactions are also effected on the coresponding 21,21-dimethyl compounds, prepared by remethylation of the 21-methyl compounds generally immediately after the first 21-methylation. The novel steroids are anti-inflammatory agents and they may be made up into standard pharmaceutical compositions.
GB33149/73A 1973-07-11 1973-07-11 Alkylated pregnanes Expired GB1478968A (en)

Priority Applications (16)

Application Number Priority Date Filing Date Title
GB33149/73A GB1478968A (en) 1973-07-11 1973-07-11 Alkylated pregnanes
IE1428/74A IE39593B1 (en) 1973-07-11 1974-07-05 Novel alkylated pregnanes
ZA00744381A ZA744381B (en) 1973-07-11 1974-07-08 Novel alkylated pregnanes and process for obtaining same
FI742103A FI52100C (en) 1973-07-11 1974-07-09 A process for the preparation of new 21-position alkylated steroids belonging to the pregnane series.
AU71040/74A AU487996B2 (en) 1974-07-09 Novel alkylated pregnanes and process for obtaining same
SE7409046A SE402920B (en) 1973-07-11 1974-07-10 PROCEDURE FOR PREPARING NEW 21-ALKYLATED 16ALFA, 17ALFA-ALKYLIDEN DIOXY-PREGN-4-EN-3,20-DIONER
DE2433178A DE2433178A1 (en) 1973-07-11 1974-07-10 PREGNAN SERIES ALKYLATED STEROIDS IN THE 21 POSITION
JP49079023A JPS5047968A (en) 1973-07-11 1974-07-10
CA204,503A CA1050529A (en) 1973-07-11 1974-07-10 Alkylated pregnanes and process for obtaining same
DK371174AA DK134700B (en) 1973-07-11 1974-07-10 Analogous process for the preparation of 21-alkylated 16alpha, 17alpha-alkylidenedioxy-pregn-4-ene-3,20-diones.
NL7409298A NL7409298A (en) 1973-07-11 1974-07-10 PROCEDURE FOR PREPARING NEW ALKYLATED STEROIDS OF THE PREGNAN SERIES.
ES428132A ES428132A1 (en) 1973-07-11 1974-07-10 Alkylated pregnanes
BE146467A BE817543A (en) 1973-07-11 1974-07-11 NEW ALKYLATED STEROIDS OF THE PREGNAN SERIES AND METHOD FOR PREPARING THEM
HU74AO00000386A HU171711B (en) 1973-07-11 1974-07-11 Process for producing 16-alpha,-17-alpha-alkylidenedioxy-21-alkyl-steroides of pregnane-group
FR7424189A FR2236508B1 (en) 1973-07-11 1974-07-11
US05/663,893 US4031075A (en) 1973-07-11 1976-03-04 Alkylated pregnanes and process for obtaining same

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
GB33149/73A GB1478968A (en) 1973-07-11 1973-07-11 Alkylated pregnanes

Publications (1)

Publication Number Publication Date
GB1478968A true GB1478968A (en) 1977-07-06

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ID=10349189

Family Applications (1)

Application Number Title Priority Date Filing Date
GB33149/73A Expired GB1478968A (en) 1973-07-11 1973-07-11 Alkylated pregnanes

Country Status (14)

Country Link
JP (1) JPS5047968A (en)
BE (1) BE817543A (en)
CA (1) CA1050529A (en)
DE (1) DE2433178A1 (en)
DK (1) DK134700B (en)
ES (1) ES428132A1 (en)
FI (1) FI52100C (en)
FR (1) FR2236508B1 (en)
GB (1) GB1478968A (en)
HU (1) HU171711B (en)
IE (1) IE39593B1 (en)
NL (1) NL7409298A (en)
SE (1) SE402920B (en)
ZA (1) ZA744381B (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4260605A (en) * 1979-01-24 1981-04-07 Akzo N.V. Novel alkylated pregnanes, processes for their preparation and pharmaceutical compositions containing same

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IT1134455B (en) * 1980-11-26 1986-08-13 Lepetit Spa PROCEDURE FOR THE PREPARATION OF 16ALPHA-HYDROXY-17ALPHA-AMINOPREGNANIC DERIVATIVES
WO1991014700A2 (en) * 1990-03-27 1991-10-03 Schering Corporation PROCESS FOR 9α-HYDROXY STEROID DEHYDRATION

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3064017A (en) * 1962-11-13 Preparation viii
GB1416427A (en) * 1972-01-12 1975-12-03 Akzo Nv Alkylated pregnanes and process for obtaining same

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4260605A (en) * 1979-01-24 1981-04-07 Akzo N.V. Novel alkylated pregnanes, processes for their preparation and pharmaceutical compositions containing same

Also Published As

Publication number Publication date
FR2236508A1 (en) 1975-02-07
DE2433178A1 (en) 1975-01-30
BE817543A (en) 1975-01-13
HU171711B (en) 1978-03-28
IE39593L (en) 1975-01-11
IE39593B1 (en) 1978-11-22
FR2236508B1 (en) 1978-07-28
CA1050529A (en) 1979-03-13
DK371174A (en) 1975-03-17
ZA744381B (en) 1975-07-30
DK134700C (en) 1977-07-11
FI52100B (en) 1977-02-28
JPS5047968A (en) 1975-04-28
FI52100C (en) 1977-06-10
FI210374A (en) 1975-01-12
SE7409046L (en) 1975-01-13
ES428132A1 (en) 1976-07-16
DK134700B (en) 1976-12-27
SE402920B (en) 1978-07-24
AU7104074A (en) 1976-01-15
NL7409298A (en) 1975-01-14

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Legal Events

Date Code Title Description
PS Patent sealed [section 19, patents act 1949]
PCNP Patent ceased through non-payment of renewal fee