FI107925B - Menetelmä aromataasi- ja 19-hydroksylaasi-inhibiittoreina käyttökelpoisten 2,19-metyleenioksi- ja 2,19-metyleenitiosilloitettujen steroidien valmistamiseksi - Google Patents
Menetelmä aromataasi- ja 19-hydroksylaasi-inhibiittoreina käyttökelpoisten 2,19-metyleenioksi- ja 2,19-metyleenitiosilloitettujen steroidien valmistamiseksi Download PDFInfo
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- FI107925B FI107925B FI906269A FI906269A FI107925B FI 107925 B FI107925 B FI 107925B FI 906269 A FI906269 A FI 906269A FI 906269 A FI906269 A FI 906269A FI 107925 B FI107925 B FI 107925B
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- 238000010521 absorption reaction Methods 0.000 description 1
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- 229920000615 alginic acid Polymers 0.000 description 1
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- 150000004781 alginic acids Chemical class 0.000 description 1
- CWNKMHIETKEBCA-UHFFFAOYSA-N alpha-Ethylaminohexanophenone Chemical compound CCCCC(NCC)C(=O)C1=CC=CC=C1 CWNKMHIETKEBCA-UHFFFAOYSA-N 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
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- 239000012223 aqueous fraction Substances 0.000 description 1
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- 239000000969 carrier Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
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- 239000002024 ethyl acetate extract Substances 0.000 description 1
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- 238000004811 liquid chromatography Methods 0.000 description 1
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- 229910052744 lithium Inorganic materials 0.000 description 1
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- KFOPKOFKGJJEBW-ZSSYTAEJSA-N methyl 2-[(1s,7r,8s,9s,10r,13r,14s,17r)-1,7-dihydroxy-10,13-dimethyl-3-oxo-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl]acetate Chemical compound C([C@H]1O)C2=CC(=O)C[C@H](O)[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](CC(=O)OC)[C@@]1(C)CC2 KFOPKOFKGJJEBW-ZSSYTAEJSA-N 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
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- 230000002107 myocardial effect Effects 0.000 description 1
- 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 description 1
- 229910052754 neon Inorganic materials 0.000 description 1
- GKAOGPIIYCISHV-UHFFFAOYSA-N neon atom Chemical compound [Ne] GKAOGPIIYCISHV-UHFFFAOYSA-N 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
- 239000010502 orange oil Substances 0.000 description 1
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- 229940037129 plain mineralocorticoids for systemic use Drugs 0.000 description 1
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- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
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- 229920001592 potato starch Polymers 0.000 description 1
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- 238000011533 pre-incubation Methods 0.000 description 1
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- 108090000623 proteins and genes Proteins 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
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- 230000003637 steroidlike Effects 0.000 description 1
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- 150000003464 sulfur compounds Chemical class 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J53/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton has been modified by condensation with a carbocyclic rings or by formation of an additional ring by means of a direct link between two ring carbon atoms, including carboxyclic rings fused to the cyclopenta(a)hydrophenanthrene skeleton are included in this class
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J71/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton is condensed with a heterocyclic ring
- C07J71/0073—Sulfur-containing hetero ring
- C07J71/0078—Sulfur-containing hetero ring containing only sulfur
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Steroid Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US45344189A | 1989-12-20 | 1989-12-20 | |
| US45344189 | 1989-12-20 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI906269A0 FI906269A0 (fi) | 1990-12-19 |
| FI906269L FI906269L (fi) | 1991-06-21 |
| FI107925B true FI107925B (fi) | 2001-10-31 |
Family
ID=23800602
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI906269A FI107925B (fi) | 1989-12-20 | 1990-12-19 | Menetelmä aromataasi- ja 19-hydroksylaasi-inhibiittoreina käyttökelpoisten 2,19-metyleenioksi- ja 2,19-metyleenitiosilloitettujen steroidien valmistamiseksi |
Country Status (20)
| Country | Link |
|---|---|
| EP (1) | EP0434020B1 (da) |
| JP (1) | JP2922653B2 (da) |
| KR (1) | KR100187781B1 (da) |
| CN (1) | CN1035768C (da) |
| AR (1) | AR248410A1 (da) |
| AT (1) | ATE124417T1 (da) |
| AU (1) | AU630008B2 (da) |
| CA (1) | CA2032311C (da) |
| DE (1) | DE69020520T2 (da) |
| DK (1) | DK0434020T3 (da) |
| ES (1) | ES2076286T3 (da) |
| FI (1) | FI107925B (da) |
| GR (1) | GR3017136T3 (da) |
| HU (1) | HU208024B (da) |
| IE (1) | IE67557B1 (da) |
| IL (1) | IL96695A (da) |
| NO (1) | NO177676C (da) |
| NZ (1) | NZ236473A (da) |
| PT (1) | PT96258B (da) |
| ZA (1) | ZA9010082B (da) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5491136A (en) * | 1989-12-20 | 1996-02-13 | Merrell Dow Pharmaceuticals Inc. | 2,19-methyleneoxy and 2,19-methylenethio bridged steroids as aromatase, 19-hydroxylaser inhibitors and methods of their use in the treatment of estrogen mediated disorders |
| US5126488A (en) * | 1990-11-30 | 1992-06-30 | Merrell Dow Pharmaceuticals Inc. | 2β,19-methyleneamino bridged steroids as aromatase inhibitors |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3627756A (en) * | 1970-04-23 | 1971-12-14 | Searle & Co | N-dialkylaminoalkyl-n-(2{62 ,19-epoxy-5{60 -androstan-17{62 -yl)amines/formamides and 3{60 -halo derivatives thereof |
| US3954980A (en) * | 1971-10-19 | 1976-05-04 | Derek Harold Richard Barton | Chemical compounds |
| US4814324A (en) * | 1987-03-06 | 1989-03-21 | Merck & Co., Inc. | Sterol inhibitors of testosterone 5α-reductase |
-
1990
- 1990-12-14 ZA ZA9010082A patent/ZA9010082B/xx unknown
- 1990-12-14 CA CA002032311A patent/CA2032311C/en not_active Expired - Fee Related
- 1990-12-14 NZ NZ236473A patent/NZ236473A/xx unknown
- 1990-12-14 AU AU68083/90A patent/AU630008B2/en not_active Ceased
- 1990-12-17 IL IL9669590A patent/IL96695A/en not_active IP Right Cessation
- 1990-12-17 HU HU908299A patent/HU208024B/hu not_active IP Right Cessation
- 1990-12-18 KR KR1019900020871A patent/KR100187781B1/ko not_active Expired - Fee Related
- 1990-12-19 JP JP2411707A patent/JP2922653B2/ja not_active Expired - Fee Related
- 1990-12-19 EP EP90124739A patent/EP0434020B1/en not_active Expired - Lifetime
- 1990-12-19 IE IE459790A patent/IE67557B1/en not_active IP Right Cessation
- 1990-12-19 CN CN90110133A patent/CN1035768C/zh not_active Expired - Fee Related
- 1990-12-19 DE DE69020520T patent/DE69020520T2/de not_active Expired - Fee Related
- 1990-12-19 DK DK90124739.5T patent/DK0434020T3/da active
- 1990-12-19 PT PT96258A patent/PT96258B/pt not_active IP Right Cessation
- 1990-12-19 ES ES90124739T patent/ES2076286T3/es not_active Expired - Lifetime
- 1990-12-19 AT AT90124739T patent/ATE124417T1/de not_active IP Right Cessation
- 1990-12-19 NO NO905494A patent/NO177676C/no not_active IP Right Cessation
- 1990-12-19 FI FI906269A patent/FI107925B/fi not_active IP Right Cessation
- 1990-12-20 AR AR90318689A patent/AR248410A1/es active
-
1995
- 1995-08-16 GR GR950402256T patent/GR3017136T3/el unknown
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM | Patent lapsed |
Owner name: MERRELL PHARMACEUTICALS, INC. |