IE39593B1 - Novel alkylated pregnanes - Google Patents

Novel alkylated pregnanes

Info

Publication number
IE39593B1
IE39593B1 IE1428/74A IE142874A IE39593B1 IE 39593 B1 IE39593 B1 IE 39593B1 IE 1428/74 A IE1428/74 A IE 1428/74A IE 142874 A IE142874 A IE 142874A IE 39593 B1 IE39593 B1 IE 39593B1
Authority
IE
Ireland
Prior art keywords
methyl
dione
hydroxy
pregnen
pregnadiene
Prior art date
Application number
IE1428/74A
Other versions
IE39593L (en
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
Publication of IE39593L publication Critical patent/IE39593L/en
Publication of IE39593B1 publication Critical patent/IE39593B1/en

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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

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  • 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. [GB1478968A]
IE1428/74A 1973-07-11 1974-07-05 Novel alkylated pregnanes IE39593B1 (en)

Applications Claiming Priority (1)

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

Publications (2)

Publication Number Publication Date
IE39593L IE39593L (en) 1975-01-11
IE39593B1 true IE39593B1 (en) 1978-11-22

Family

ID=10349189

Family Applications (1)

Application Number Title Priority Date Filing Date
IE1428/74A IE39593B1 (en) 1973-07-11 1974-07-05 Novel alkylated pregnanes

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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)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3064460D1 (en) * 1979-01-24 1983-09-08 Akzo Nv Novel alkylated pregnanes, processes for their preparation and pharmaceutical compositions containing same
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

Also Published As

Publication number Publication date
CA1050529A (en) 1979-03-13
AU7104074A (en) 1976-01-15
DK371174A (en) 1975-03-17
FI52100B (en) 1977-02-28
FR2236508B1 (en) 1978-07-28
NL7409298A (en) 1975-01-14
FI52100C (en) 1977-06-10
SE7409046L (en) 1975-01-13
FR2236508A1 (en) 1975-02-07
IE39593L (en) 1975-01-11
HU171711B (en) 1978-03-28
SE402920B (en) 1978-07-24
DE2433178A1 (en) 1975-01-30
FI210374A (en) 1975-01-12
JPS5047968A (en) 1975-04-28
DK134700B (en) 1976-12-27
DK134700C (en) 1977-07-11
ES428132A1 (en) 1976-07-16
ZA744381B (en) 1975-07-30
BE817543A (en) 1975-01-13
GB1478968A (en) 1977-07-06

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