GB1215752A - Novel halogenated steroids and a process for the manufacture thereof - Google Patents
Novel halogenated steroids and a process for the manufacture thereofInfo
- Publication number
- GB1215752A GB1215752A GB37510/68A GB3751068A GB1215752A GB 1215752 A GB1215752 A GB 1215752A GB 37510/68 A GB37510/68 A GB 37510/68A GB 3751068 A GB3751068 A GB 3751068A GB 1215752 A GB1215752 A GB 1215752A
- Authority
- GB
- United Kingdom
- Prior art keywords
- acetoxy
- chloro
- trione
- pregna
- diene
- 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
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J1/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, not substituted in position 17 beta by a carbon atom, e.g. estrane, androstane
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J5/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J7/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Steroid Compounds (AREA)
Abstract
1,215,752. 4-Chloro-steroids. F. HOFFMANNLA ROCHE & CO. A.G. 6 Aug., 1968 [7 Aug., 1967], No. 37510/68. Heading C2U. The invention comprises steroids of formula wherein R<SP>1</SP> is F, Cl, Br or C 1-8 alkyl, and A represents one of the following entities wherein R<SP>2</SP> is H or F; R<SP>3</SP> is H, OH, C 1-8 alkoxy, C 1-8 alkanoyloxy, COCHF 2 , COCHCl 2 or C 1-8 alkyl; R<SP>4</SP> is C 1-7 alkylidene or α-CH 2 Cl, (the latter, only when n is 0 or 1, X is a #<SP>1</SP>-unsaturation or 2-chloro group, R<SP>2</SP> is H and R<SP>3</SP> is OH or C 1-8 alkanoyloxy); or R<SP>3</SP> + R<SP>4</SP> together form a 1<SP>1</SP>-alkyl-alkylidenedioxy group; R<SP>5</SP> is H or C 1-8 alkanoyl; R<SP>6</SP> is H, C 1-8 alkyl or optionally halo-substituted C 2-7 monounsaturated aliphatic hydrocarbyl; R<SP>7</SP> is H or CH 3 ; R<SP>8</SP> is α-H, α-F, α-Cl or α-Br; R<SP>9</SP> is H, a hydroxy group, the dihydrogen phosphate ester thereof or an alkali metal salt thereof, or a C 1-8 alkanoyloxy group; R<SP>10</SP> is C 1-7 alkylidene, α-CH 2 Cl, α-CH 2 F, α-Cl or α-F; R<SP>11</SP> is OH or C 1-8 alkanoyloxy; or, when R<SP>9</SP> is H, R<SP>10</SP> + R<SP>11</SP> together form a 1<SP>1</SP>-alkylalkylidenedioxy group; or R<SP>9</SP> + R<SP>11</SP> together form a 1<SP>1</SP>-alkoxy-alkylidenedioxy group; n is 0 or 1; X is a #<SP>1</SP>-unsaturation or a 2-chloro or 1α,2α-methylene group; X<SP>1</SP> is a #<SP>1</SP>-unsaturation or a 2-chloro group; Y is CH 2 , CHOH or CO; Z is CHOH, CO, α-(alkyl- or aryl-sulphonyloxy) - methylene or, (when R<SP>8</SP> is α-H and R<SP>9</SP> is other than H), methylene, or, (when R<SP>8</SP> = Cl), #-chloromethylene; or x + R<SP>8</SP> together represent a #<SP>9</SP>(<SP>11</SP>)-unsaturation or a 9#, 11#-epoxy group. The above compounds are prepared (i) by chlorination of the corresponding 4-unsubstituted compounds; and (ii) the action of a strong acid on a steroid of formula to obtain the corresponding 16-methylene-17α- hydroxy-steroid. Product interconversions described are 2-chlorination; 1,2-dehydrogenation; oxidation of 11-OH to 11-OXO; sulphonation of 11α-OH; dehydration of a 9α-H-11#-OH compound or desulphonation of a 9α-H-11α- sulphonyloxy compound to yield a #<SP>9</SP>(<SP>11</SP>)- compound; treatment of #<SP>9</SP>(<SP>11</SP>)-compounds with HOCl or HOBr to give 9α-(Cl or Br)-11-OH compounds; dehydrohalogenating 9α-(Cl or Br)-11-OH compounds to 9#,11#-epoxy compounds; treatment of 9#,11#-epoxy compounds with HF, HCl, HBr or a chlorinating agent to give 9α-halo-11-OH or 9α,11#-dichloro compounds; esterification of 17- and/or 21-hydroxy groups; and saponification of 17- and/or 21-alkanoyloxy groups. 6 - Fluoro - 16α,17α - isopropylidenedioxypregna - 4,6 - diene - 3,11,20 - trione, 21 - acetoxy - 6 - fluoro - 16α - fluoromethyl - 17α - hydroxy - pregna - 4,6 - diene 3,11,20 - triene and 21 - acetoxy - 6,16α - difluoro - 17α - hydroxypregna - 4,6 - diene - 3,11,20 - trione are prepared by 6,7-dehydrogenation of the corresponding pregn-4-enes. 6 - Chloro - 16α - chloromethyl - 17α - acetoxypregna - 4,6 - diene - 3,20 - dione is prepared from 16α - chloromethyl - 17α - acetoxy - pregn- 4 - ene - 3,20 - dione via 17α - acetoxy - 16α chloromethyl - 3 - ethoxy - pregna - 3,5 - dien - 20- one and 6# - chloro - 16α - chloromethyl - 17α- acetoxy - pregn - 4 - ene - 3,20 - dione. 21 - Acetoxy - 6 - chloro - 17α - hydroxy - 16- methylene - pregna - 4,6 - diene - 3,11,20 - trione is prepared from 21-acetoxy-17α-hydroxy-16- methylene - pregn - 4 - ene - 3,11,20 - trione via 21 - acetoxy - 3 - ethoxy - 17α - hydroxy - 16- methylene - pregna - 3,5 - diene - 11,20 - dione and 21 - acetoxy - 6# - chloro - 17α - hydroxy - 16- methylene - pregn - 4 - ene - 3,11,20 - trione. 4,6 - Dichloro - 21 - acetoxy - 16α,17α - epoxy- 16# - methyl - pregna - 4,6 - diene - 3,11,20- trione (X) is prepared by the sequence: 21- acetoxy - 6 - chloro - 17α - hydroxy - pregna - 4,6- diene - 3,11,20 - trione (XI) # the 3,20 - bis- (semicarbazone) of XI # 21 - acetoxy - 6- chloro - pregna - 4,6,16 - triene - 3,11,20 - trione 3,20 - bis(semicarbazone) # 21 - hydroxy - 6- chloro - pregna - 4,6,16 - triene - 3,11,20 - trione (XII) # the 21-acetate of XII # 6-chloro-21- acetoxy - 16α,17α - methyleneazo - pregna - 4,6- diene - 3,11,20 - trione # 6 - chloro - 21 - acetoxy - 16 - methyl - pregna - 4,6,16 - triene- 3,11,20 - trione # an unidentified trichloro intermediate (by treatment with Cl 2 /CCl 4 ) # an unidentified oil (by treatment with Na 2 HPO 4 / CF 3 CO 3 H) # X (by treatment with pyridine). 2#,4,6 - Trichloro - 21 - acetoxy - 16α,17α- epoxy - 16# - methyl - pregna - 4,6 - diene- 3,11,20-trione is prepared by chlorination of the corresponding 2-dechloro compound. The compounds of Formula I are stated to possess progestational, glucocorticoid, mineralocorticoid, anti inflammatory and thymolytic activities, and may be made up with carriers into pharmaceutical compositions for oral, parenteral and topical administration.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US65860267A | 1967-08-07 | 1967-08-07 |
Publications (1)
Publication Number | Publication Date |
---|---|
GB1215752A true GB1215752A (en) | 1970-12-16 |
Family
ID=24641922
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
GB37509/68A Expired GB1217530A (en) | 1967-08-07 | 1968-08-06 | Novel halogenated steroids and a process for the manufacture thereof |
GB37510/68A Expired GB1215752A (en) | 1967-08-07 | 1968-08-06 | Novel halogenated steroids and a process for the manufacture thereof |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
GB37509/68A Expired GB1217530A (en) | 1967-08-07 | 1968-08-06 | Novel halogenated steroids and a process for the manufacture thereof |
Country Status (17)
Country | Link |
---|---|
JP (2) | JPS5021474B1 (en) |
AT (4) | AT290030B (en) |
BE (2) | BE719049A (en) |
CH (10) | CH544074A (en) |
DE (1) | DE1793063A1 (en) |
DK (2) | DK126187B (en) |
ES (2) | ES356956A1 (en) |
FI (2) | FI45321C (en) |
FR (4) | FR7921M (en) |
GB (2) | GB1217530A (en) |
IE (2) | IE32397B1 (en) |
IL (2) | IL30492A (en) |
MY (1) | MY7100216A (en) |
NL (2) | NL6811217A (en) |
NO (2) | NO128766B (en) |
SE (2) | SE351633B (en) |
YU (2) | YU33190B (en) |
-
1968
- 1968-07-17 CH CH418971A patent/CH544074A/en not_active IP Right Cessation
- 1968-07-17 CH CH418571A patent/CH541549A/en not_active IP Right Cessation
- 1968-07-17 CH CH418871A patent/CH544072A/en not_active IP Right Cessation
- 1968-07-17 CH CH1070668A patent/CH555329A/en not_active IP Right Cessation
- 1968-07-17 CH CH419271A patent/CH544076A/en not_active IP Right Cessation
- 1968-07-17 CH CH418671A patent/CH544075A/en not_active IP Right Cessation
- 1968-07-17 CH CH419071A patent/CH541550A/en not_active IP Right Cessation
- 1968-07-17 CH CH419171A patent/CH544081A/en not_active IP Right Cessation
- 1968-07-17 CH CH1070568A patent/CH565198A5/xx not_active IP Right Cessation
- 1968-07-17 CH CH418771A patent/CH544073A/en not_active IP Right Cessation
- 1968-07-30 DE DE19681793063 patent/DE1793063A1/en active Pending
- 1968-08-05 AT AT888169A patent/AT290030B/en not_active IP Right Cessation
- 1968-08-05 AT AT760368A patent/AT285832B/en not_active IP Right Cessation
- 1968-08-05 AT AT08882/69A patent/AT290031B/en not_active IP Right Cessation
- 1968-08-05 AT AT760468A patent/AT285833B/en not_active IP Right Cessation
- 1968-08-05 BE BE719049D patent/BE719049A/xx unknown
- 1968-08-05 BE BE719050D patent/BE719050A/xx unknown
- 1968-08-05 IL IL30492A patent/IL30492A/en unknown
- 1968-08-05 YU YU1858/68A patent/YU33190B/en unknown
- 1968-08-05 IL IL6830491A patent/IL30491A/en unknown
- 1968-08-05 YU YU01857/68A patent/YU185768A/en unknown
- 1968-08-06 DK DK379168AA patent/DK126187B/en unknown
- 1968-08-06 FR FR162042A patent/FR7921M/fr not_active Expired
- 1968-08-06 GB GB37509/68A patent/GB1217530A/en not_active Expired
- 1968-08-06 JP JP43055307A patent/JPS5021474B1/ja active Pending
- 1968-08-06 NO NO03088/68A patent/NO128766B/no unknown
- 1968-08-06 GB GB37510/68A patent/GB1215752A/en not_active Expired
- 1968-08-06 IE IE950/68A patent/IE32397B1/en unknown
- 1968-08-06 NO NO03087/68A patent/NO128765B/no unknown
- 1968-08-06 FR FR162043A patent/FR8417M/fr not_active Expired
- 1968-08-06 IE IE949/68A patent/IE32344B1/en unknown
- 1968-08-06 FR FR1588548D patent/FR1588548A/fr not_active Expired
- 1968-08-06 ES ES356956A patent/ES356956A1/en not_active Expired
- 1968-08-06 DK DK379268AA patent/DK122606B/en unknown
- 1968-08-06 FR FR1588547D patent/FR1588547A/fr not_active Expired
- 1968-08-06 ES ES356957A patent/ES356957A1/en not_active Expired
- 1968-08-07 SE SE10631/68A patent/SE351633B/xx unknown
- 1968-08-07 NL NL6811217A patent/NL6811217A/xx unknown
- 1968-08-07 NL NL6811218A patent/NL6811218A/xx unknown
- 1968-08-07 FI FI682233A patent/FI45321C/en active
- 1968-08-07 JP JP43055539A patent/JPS5010859B1/ja active Pending
- 1968-08-07 FI FI682234A patent/FI45322C/en active
- 1968-08-07 SE SE10630/68A patent/SE351632B/xx unknown
-
1971
- 1971-12-30 MY MY216/71A patent/MY7100216A/en unknown
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