IL108632A - Fluorinated 4-aminoandrostadienone derivatives, their preparation and pharmaceutical compositions containing them - Google Patents

Fluorinated 4-aminoandrostadienone derivatives, their preparation and pharmaceutical compositions containing them

Info

Publication number: IL108632A
Authority: IL; Israel
Prior art keywords: compound; formula; dione; androsta; amino
Prior art date: 1993-02-18

Application number

IL108632A

Other languages

English (en)

Hebrew (he)

Other versions

IL108632A0 (en

Inventor

Franco Buzzetti

Antonio Longo

Enrico Di Salle

Original Assignee

Pharmacia & Upjohn Spa

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.)

1993-02-18

Filing date

1994-02-14

Publication date

1998-06-15

1993-02-18 Priority claimed from GB939303306A external-priority patent/GB9303306D0/en

1993-10-29 Priority claimed from GB939322378A external-priority patent/GB9322378D0/en

1994-02-14 Application filed by Pharmacia & Upjohn Spa filed Critical Pharmacia & Upjohn Spa

1994-05-30 Publication of IL108632A0 publication Critical patent/IL108632A0/xx

1998-06-15 Publication of IL108632A publication Critical patent/IL108632A/en

Links

229910052731 fluorine Inorganic materials 0.000 title claims description 27
239000011737 fluorine Substances 0.000 title claims description 27
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 title claims description 15
238000002360 preparation method Methods 0.000 title claims description 8
239000000825 pharmaceutical preparation Substances 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims description 163
239000000203 mixture Substances 0.000 claims description 47
OSVMTWJCGUFAOD-KZQROQTASA-N formestane Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1O OSVMTWJCGUFAOD-KZQROQTASA-N 0.000 claims description 46
238000000034 method Methods 0.000 claims description 41
125000002252 acyl group Chemical group 0.000 claims description 38
229910052739 hydrogen Inorganic materials 0.000 claims description 37
239000001257 hydrogen Substances 0.000 claims description 37
150000003839 salts Chemical class 0.000 claims description 20
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 18
-1 azido compound Chemical class 0.000 claims description 16
KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 claims description 14
125000001153 fluoro group Chemical group F* 0.000 claims description 12
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 12
150000002431 hydrogen Chemical group 0.000 claims description 11
150000002118 epoxides Chemical class 0.000 claims description 10
229910000040 hydrogen fluoride Inorganic materials 0.000 claims description 10
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 8
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
238000005917 acylation reaction Methods 0.000 claims description 7
238000003776 cleavage reaction Methods 0.000 claims description 7
230000007017 scission Effects 0.000 claims description 7
230000010933 acylation Effects 0.000 claims description 6
239000008194 pharmaceutical composition Substances 0.000 claims description 6
238000005576 amination reaction Methods 0.000 claims description 5
239000003886 aromatase inhibitor Substances 0.000 claims description 5
229940122815 Aromatase inhibitor Drugs 0.000 claims description 4
238000005947 deacylation reaction Methods 0.000 claims description 4
239000003814 drug Substances 0.000 claims description 4
238000003682 fluorination reaction Methods 0.000 claims description 4
ZZQMHWCDBFFHJL-UXTYWDKOSA-N (6s,8r,9s,10r,13s,14s)-4-amino-6-fluoro-10,13-dimethyl-7,8,9,11,12,14,15,16-octahydro-6h-cyclopenta[a]phenanthrene-3,17-dione Chemical compound O=C1C=C[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3C[C@H](F)C2=C1N ZZQMHWCDBFFHJL-UXTYWDKOSA-N 0.000 claims description 3
STOAIISZONPGDM-QCVUSQAGSA-N (6s,8r,9s,10s,13s,14s)-4-amino-2,6-difluoro-10,13-dimethyl-7,8,9,11,12,14,15,16-octahydro-6h-cyclopenta[a]phenanthrene-3,17-dione Chemical compound O=C1C(F)=C[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3C[C@H](F)C2=C1N STOAIISZONPGDM-QCVUSQAGSA-N 0.000 claims description 3
MLRZGQCKJXVEFK-QRHVUTMTSA-N (8r,9s,10s,13s,14s)-4-amino-2,6-difluoro-10,13-dimethyl-9,11,12,14,15,16-hexahydro-8h-cyclopenta[a]phenanthrene-3,17-dione Chemical compound O=C1C(F)=C[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3C=C(F)C2=C1N MLRZGQCKJXVEFK-QRHVUTMTSA-N 0.000 claims description 3
230000006179 O-acylation Effects 0.000 claims description 3
239000003085 diluting agent Substances 0.000 claims description 3
SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 claims description 3
ZZQMHWCDBFFHJL-ZNSHXGERSA-N (8r,9s,10r,13s,14s)-4-amino-6-fluoro-10,13-dimethyl-7,8,9,11,12,14,15,16-octahydro-6h-cyclopenta[a]phenanthrene-3,17-dione Chemical compound O=C1C=C[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC(F)C2=C1N ZZQMHWCDBFFHJL-ZNSHXGERSA-N 0.000 claims description 2
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 40
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238000006243 chemical reaction Methods 0.000 description 27
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235000019439 ethyl acetate Nutrition 0.000 description 16
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229940011871 estrogen Drugs 0.000 description 11
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RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 8
238000001816 cooling Methods 0.000 description 8
229940093499 ethyl acetate Drugs 0.000 description 8
238000010992 reflux Methods 0.000 description 8
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 7
239000007864 aqueous solution Substances 0.000 description 7
238000003818 flash chromatography Methods 0.000 description 7
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Substances [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 7
239000012044 organic layer Substances 0.000 description 7
239000003960 organic solvent Substances 0.000 description 7
MTPYNCIHUMKJFJ-RUVCREKUSA-N (8r,9s,10s,13s,14s)-4-amino-2-fluoro-10,13-dimethyl-9,11,12,14,15,16-hexahydro-8h-cyclopenta[a]phenanthrene-3,17-dione Chemical compound O=C1C(F)=C[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3C=CC2=C1N MTPYNCIHUMKJFJ-RUVCREKUSA-N 0.000 description 6
102000014654 Aromatase Human genes 0.000 description 6
108010078554 Aromatase Proteins 0.000 description 6
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PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
230000001419 dependent effect Effects 0.000 description 6
238000006735 epoxidation reaction Methods 0.000 description 6
239000000047 product Substances 0.000 description 6
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
239000011541 reaction mixture Substances 0.000 description 6
239000000725 suspension Substances 0.000 description 6
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 6
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 5
229920002261 Corn starch Polymers 0.000 description 5
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
239000003795 chemical substances by application Substances 0.000 description 5
239000008120 corn starch Substances 0.000 description 5
229910000029 sodium carbonate Inorganic materials 0.000 description 5
150000003431 steroids Chemical class 0.000 description 5
125000001424 substituent group Chemical group 0.000 description 5
BROHIGNLIJDZRZ-RUVCREKUSA-N (8r,9s,10r,13s,14s)-4-amino-6-fluoro-10,13-dimethyl-9,11,12,14,15,16-hexahydro-8h-cyclopenta[a]phenanthrene-3,17-dione Chemical compound O=C1C=C[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3C=C(F)C2=C1N BROHIGNLIJDZRZ-RUVCREKUSA-N 0.000 description 4
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PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
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239000002775 capsule Substances 0.000 description 4
RBHJBMIOOPYDBQ-UHFFFAOYSA-N carbon dioxide;propan-2-one Chemical compound O=C=O.CC(C)=O RBHJBMIOOPYDBQ-UHFFFAOYSA-N 0.000 description 4
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235000019359 magnesium stearate Nutrition 0.000 description 4
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BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
229910000027 potassium carbonate Inorganic materials 0.000 description 4
239000002904 solvent Substances 0.000 description 4
239000003826 tablet Substances 0.000 description 4
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
ONQIIHXPPFUGMC-PRRIXCOJSA-N (8S,9S,10R,13R,14S)-4-amino-10,13-dimethyl-1,2,6,7,8,9,11,12,14,15-decahydrocyclopenta[a]phenanthren-3-one Chemical class O=C1CC[C@]2(C)[C@H]3CC[C@](C)(C=CC4)[C@@H]4[C@@H]3CCC2=C1N ONQIIHXPPFUGMC-PRRIXCOJSA-N 0.000 description 3
NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 3
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230000002503 metabolic effect Effects 0.000 description 1
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150000004681 metal hydrides Chemical class 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
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230000003228 microsomal effect Effects 0.000 description 1
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238000002156 mixing Methods 0.000 description 1
239000012452 mother liquor Substances 0.000 description 1
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238000006386 neutralization reaction Methods 0.000 description 1
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229910052757 nitrogen Inorganic materials 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
208000008634 oligospermia Diseases 0.000 description 1
230000036616 oligospermia Effects 0.000 description 1
231100000528 oligospermia Toxicity 0.000 description 1
239000004006 olive oil Substances 0.000 description 1
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150000007524 organic acids Chemical class 0.000 description 1
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238000006053 organic reaction Methods 0.000 description 1
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FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
230000008506 pathogenesis Effects 0.000 description 1
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235000010987 pectin Nutrition 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
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JKPDEYAOCSQBSZ-OEUJLIAZSA-N plomestane Chemical compound O=C1CC[C@]2(CC#C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1 JKPDEYAOCSQBSZ-OEUJLIAZSA-N 0.000 description 1
201000010065 polycystic ovary syndrome Diseases 0.000 description 1
229920000136 polysorbate Polymers 0.000 description 1
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239000001267 polyvinylpyrrolidone Substances 0.000 description 1
229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
239000011591 potassium Substances 0.000 description 1
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239000000843 powder Substances 0.000 description 1
208000006155 precocious puberty Diseases 0.000 description 1
230000002265 prevention Effects 0.000 description 1
239000000651 prodrug Substances 0.000 description 1
229940002612 prodrug Drugs 0.000 description 1
ZJLMKPKYJBQJNH-UHFFFAOYSA-N propane-1,3-dithiol Chemical compound SCCCS ZJLMKPKYJBQJNH-UHFFFAOYSA-N 0.000 description 1
238000011321 prophylaxis Methods 0.000 description 1
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238000000746 purification Methods 0.000 description 1
JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical compound C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 description 1
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
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235000015424 sodium Nutrition 0.000 description 1
239000011734 sodium Substances 0.000 description 1
235000010413 sodium alginate Nutrition 0.000 description 1
239000000661 sodium alginate Substances 0.000 description 1
229940005550 sodium alginate Drugs 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
229940001584 sodium metabisulfite Drugs 0.000 description 1
235000010262 sodium metabisulphite Nutrition 0.000 description 1
229920003109 sodium starch glycolate Polymers 0.000 description 1
229940079832 sodium starch glycolate Drugs 0.000 description 1
239000008109 sodium starch glycolate Substances 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
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239000004094 surface-active agent Substances 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
GFYHSKONPJXCDE-UHFFFAOYSA-N sym-collidine Natural products CC1=CN=C(C)C(C)=C1 GFYHSKONPJXCDE-UHFFFAOYSA-N 0.000 description 1
229960003604 testosterone Drugs 0.000 description 1
UGNWTBMOAKPKBL-UHFFFAOYSA-N tetrachloro-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(Cl)=C(Cl)C1=O UGNWTBMOAKPKBL-UHFFFAOYSA-N 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
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VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
238000001665 trituration Methods 0.000 description 1
238000005303 weighing Methods 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
- C07J41/0005—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring the nitrogen atom being directly linked to the cyclopenta(a)hydro phenanthrene skeleton
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
- 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
- A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
- 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
- C07J1/0003—Androstane derivatives
- C07J1/0011—Androstane derivatives substituted in position 17 by a keto group
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
- C07J41/0005—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring the nitrogen atom being directly linked to the cyclopenta(a)hydro phenanthrene skeleton
- C07J41/0011—Unsubstituted amino radicals
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
- C07J41/0005—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring the nitrogen atom being directly linked to the cyclopenta(a)hydro phenanthrene skeleton
- C07J41/0027—Azides
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J71/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton is condensed with a heterocyclic ring
- C07J71/0005—Oxygen-containing hetero ring
- C07J71/001—Oxiranes

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
General Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Life Sciences & Earth Sciences (AREA)
Epidemiology (AREA)
Pharmacology & Pharmacy (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Medicinal Chemistry (AREA)
Steroid Compounds (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

IL108632A 1993-02-18 1994-02-14 Fluorinated 4-aminoandrostadienone derivatives, their preparation and pharmaceutical compositions containing them IL108632A (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
GB939303306A GB9303306D0 (en)	1993-02-18	1993-02-18	Fluorinated 4-aminoandrostendione derivatives and process for their preparation
GB939322378A GB9322378D0 (en)	1993-10-29	1993-10-29	Fluorinated 4-aminoandrostadienone derivatives and process for their preparation

Publications (2)

Publication Number	Publication Date
IL108632A0 IL108632A0 (en)	1994-05-30
IL108632A true IL108632A (en)	1998-06-15

Family

ID=26302483

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
IL108632A IL108632A (en)	1993-02-18	1994-02-14	Fluorinated 4-aminoandrostadienone derivatives, their preparation and pharmaceutical compositions containing them

Country Status (15)

Country	Link
US (1)	US5502044A (xx)
EP (1)	EP0636138A1 (xx)
JP (1)	JPH07506120A (xx)
KR (1)	KR950701341A (xx)
CN (1)	CN1102529A (xx)
AU (1)	AU666433B2 (xx)
CA (1)	CA2118317A1 (xx)
FI (1)	FI944842L (xx)
HU (1)	HUT68320A (xx)
IL (1)	IL108632A (xx)
MX (1)	MX9401172A (xx)
MY (1)	MY131544A (xx)
NZ (1)	NZ261123A (xx)
PL (1)	PL305757A1 (xx)
WO (1)	WO1994019365A1 (xx)

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US6407082B1 (en) *	1996-09-13	2002-06-18	New Life Pharmaceuticals Inc.	Prevention of ovarian cancer by administration of a vitamin D compound
US6765002B2 (en)	2000-03-21	2004-07-20	Gustavo Rodriguez	Prevention of ovarian cancer by administration of products that induce transforming growth factor-β and/or apoptosis in the ovarian epithelium
US6028064A (en) *	1996-09-13	2000-02-22	New Life Pharmaceuticals Inc.	Prevention of ovarian cancer by administration of progestin products
US6034074A (en)	1996-09-13	2000-03-07	New Life Pharmaceuticals Inc.	Prevention of ovarian cancer by administration of a Vitamin D compound
US6511970B1 (en)	1996-09-13	2003-01-28	New Life Pharmaceuticals Inc.	Prevention of ovarian cancer by administration of products that induce transforming growth factor-beta and/or apoptosis in the ovarian epithelium
US20010044431A1 (en) *	2000-03-21	2001-11-22	Rodriguez Gustavo C.	Prevention of ovarian cancer by administration of products that induce biologic effects in the ovarian epithelium
DK1377298T3 (da) *	2001-01-26	2007-01-02	Pfizer Italia Srl	Exemestan til behandling af hormon-afhængige lidelser
WO2011127232A2 (en)	2010-04-08	2011-10-13	Emory University	Substituted androst-4-ene diones
CN113105517B (zh) *	2021-04-10	2022-03-01	台州仙琚药业有限公司	雄甾-1,4,9-三烯-3,17-二酮的合成方法

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4408616A (en) *	1981-05-15	1983-10-11	The Children's Medical Center Corporation	Brain electricaL activity mapping
GB8503940D0 (en) *	1985-02-15	1985-03-20	Erba Farmitalia	4-substituted androstendione derivatives
GB8617107D0 (en) *	1986-07-14	1986-08-20	Erba Farmitalia	6-/7-methylenandrosta-1 4-diene-3 17-dione derivatives
GB8622330D0 (en) *	1986-09-17	1986-10-22	Erba Farmitalia	4-substituted 6-alkylidenandrostene-3,17-dione derivatives
GB8711579D0 (en) *	1987-05-15	1987-06-17	Erba Farmitalia	4-amino-androstenedione derivatives
GB8721384D0 (en) *	1987-09-11	1987-10-21	Erba Farmitalia	17-substituted andro-sta-1 4-dien-3-one derivatives

1994
- 1994-02-01 CA CA002118317A patent/CA2118317A1/en not_active Abandoned
- 1994-02-01 JP JP6518595A patent/JPH07506120A/ja active Pending
- 1994-02-01 CN CN94190069A patent/CN1102529A/zh active Pending
- 1994-02-01 PL PL94305757A patent/PL305757A1/xx unknown
- 1994-02-01 AU AU59726/94A patent/AU666433B2/en not_active Ceased
- 1994-02-01 KR KR1019940703688A patent/KR950701341A/ko not_active Application Discontinuation
- 1994-02-01 WO PCT/EP1994/000282 patent/WO1994019365A1/en not_active Application Discontinuation
- 1994-02-01 EP EP94905737A patent/EP0636138A1/en not_active Withdrawn
- 1994-02-01 HU HU9403294A patent/HUT68320A/hu unknown
- 1994-02-01 NZ NZ261123A patent/NZ261123A/en unknown
- 1994-02-14 US US08/195,205 patent/US5502044A/en not_active Expired - Fee Related
- 1994-02-14 IL IL108632A patent/IL108632A/en not_active IP Right Cessation
- 1994-02-15 MX MX9401172A patent/MX9401172A/es unknown
- 1994-02-17 MY MYPI94000373A patent/MY131544A/en unknown
- 1994-10-14 FI FI944842A patent/FI944842L/fi not_active Application Discontinuation

Also Published As

Publication number	Publication date
CA2118317A1 (en)	1994-09-01
FI944842A0 (fi)	1994-10-14
PL305757A1 (en)	1995-02-06
HUT68320A (en)	1995-06-28
IL108632A0 (en)	1994-05-30
JPH07506120A (ja)	1995-07-06
MX9401172A (es)	1994-08-31
NZ261123A (en)	1996-08-27
KR950701341A (ko)	1995-03-23
US5502044A (en)	1996-03-26
AU5972694A (en)	1994-09-14
AU666433B2 (en)	1996-02-08
EP0636138A1 (en)	1995-02-01
WO1994019365A1 (en)	1994-09-01
MY131544A (en)	2007-08-30
CN1102529A (zh)	1995-05-10
FI944842L (fi)	1994-10-14

Publication	Publication Date	Title
CA1319362C (en)	1993-06-22	4-substituted androstendione derivatives and process for their preparation
NL193616C (nl)	2000-04-04	Gesubstitueerde androsta-1,4-dieen-3,17-dionen, alsmede farmaceutische preparaten die dergelijke verbindingen bevatten.
US4824830A (en)	1989-04-25	6- or 7-methylenandrosta-1,4-diene-3,17-dione derivatives and process for their preparation
US5502044A (en)	1996-03-26	Fluorinated 4-aminoandrostadienone derivatives and process for their preparation
US4840943A (en)	1989-06-20	Androst-4-ene-3,17-diones and process for their preparation
US4808578A (en)	1989-02-28	6-Alkylidene 10 β-alkynylestrene derivatives and pharmaceutical methods for their use
HU197028B (en)	1989-02-28	Process for producing 6alpha-amino- and -azidosteroids and pharmaceuticals with aromatase inhibiting effect comprising the same
WO1995001366A1 (en)	1995-01-12	Fluorinated 6-methylenandrosta-1,4-dien-3-one derivatives and process for their preparation
US5457097A (en)	1995-10-10	Androst-4-eno[4,5-b]pyrrole derivatives
GB2191777A (en)	1987-12-23	Methylene derivatives of androst-4-ene-3,17-diones and process for their preparation
WO1993014105A1 (en)	1993-07-22	Difluoromethylenandrostenone derivatives and process for their preparation
GB2284605A (en)	1995-06-14	6-or 7-substituted 4-aminoandrostadienone derivatives
WO1994010190A1 (en)	1994-05-11	6,7α-DIFLUOROMETHYLENANDROSTA-1,4-DIEN-3-ONE DERIVATIVES AND PROCESS FOR THEIR PREPARATION
GB2195639A (en)	1988-04-13	Polyconjugated androstenediones and process for their preparation

Legal Events

Date	Code	Title	Description
1998-11-26	FF	Patent granted
2001-06-14	RH	Patent void