CN1106383C - 雌性激素剂 - Google Patents

雌性激素剂 Download PDF

Info

Publication number: CN1106383C
Authority: CN; China
Prior art keywords: compound; benzyl; indoles; alcohol; methyl
Prior art date: 1996-04-19
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 - Lifetime

Application number

CN97113496A

Other languages

English (en)

Chinese (zh)

Other versions

CN1170719A (zh

Inventor

C·P·米勒

M·D·科林尼

B·D·特兰

A·A·沙特利

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.)

Wyeth LLC

Original Assignee

American Home Products Corp

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.)

1996-04-19

Filing date

1997-04-18

Publication date

2003-04-23

Family has litigation

First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=27092026&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=CN1106383(C) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.

1997-04-04 Priority claimed from US08/833,271 external-priority patent/US5998402A/en

1997-04-18 Application filed by American Home Products Corp filed Critical American Home Products Corp

1998-01-21 Publication of CN1170719A publication Critical patent/CN1170719A/zh

2003-04-23 Application granted granted Critical

2003-04-23 Publication of CN1106383C publication Critical patent/CN1106383C/zh

2017-04-18 Anticipated expiration legal-status Critical

Status Expired - Lifetime legal-status Critical Current

Links

239000000262 estrogen Substances 0.000 title abstract description 5
150000001875 compounds Chemical class 0.000 claims abstract description 167
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 3
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 125
150000003839 salts Chemical class 0.000 claims description 60
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 49
229940088597 hormone Drugs 0.000 claims description 41
239000005556 hormone Substances 0.000 claims description 41
229910052736 halogen Inorganic materials 0.000 claims description 31
150000002367 halogens Chemical class 0.000 claims description 23
-1 methylene-dioxy Chemical group 0.000 claims description 23
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 20
208000035217 Ring chromosome 1 syndrome Diseases 0.000 claims description 20
125000004093 cyano group Chemical group *C#N 0.000 claims description 20
230000000694 effects Effects 0.000 claims description 20
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims description 19
229910052739 hydrogen Inorganic materials 0.000 claims description 18
229910052799 carbon Inorganic materials 0.000 claims description 14
239000000203 mixture Substances 0.000 claims description 13
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 11
125000000217 alkyl group Chemical group 0.000 claims description 10
229910052801 chlorine Inorganic materials 0.000 claims description 10
239000001257 hydrogen Substances 0.000 claims description 9
201000010099 disease Diseases 0.000 claims description 7
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 7
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 7
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 6
238000011161 development Methods 0.000 claims description 6
230000018109 developmental process Effects 0.000 claims description 6
125000000623 heterocyclic group Chemical group 0.000 claims description 6
206010065687 Bone loss Diseases 0.000 claims description 5
125000001743 benzylic group Chemical group 0.000 claims description 5
210000004696 endometrium Anatomy 0.000 claims description 5
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 claims description 5
238000004519 manufacturing process Methods 0.000 claims description 5
239000003937 drug carrier Substances 0.000 claims description 3
WZEOZJQLTRFNCU-UHFFFAOYSA-N trifluoro(trifluoromethoxy)methane Chemical class FC(F)(F)OC(F)(F)F WZEOZJQLTRFNCU-UHFFFAOYSA-N 0.000 claims description 3
208000024172 Cardiovascular disease Diseases 0.000 claims description 2
125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 2
125000004432 carbon atom Chemical group C* 0.000 claims description 2
125000005842 heteroatom Chemical group 0.000 claims description 2
206010020718 hyperplasia Diseases 0.000 claims description 2
229950010765 pivalate Drugs 0.000 claims description 2
125000005547 pivalate group Chemical group 0.000 claims description 2
208000011580 syndromic disease Diseases 0.000 claims description 2
125000004122 cyclic group Chemical group 0.000 claims 2
ISWSIDIOOBJBQZ-UHFFFAOYSA-M phenolate Chemical compound [O-]C1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-M 0.000 claims 2
229940031826 phenolate Drugs 0.000 claims 2
239000003814 drug Substances 0.000 claims 1
238000000034 method Methods 0.000 abstract description 62
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 304
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical group CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 111
238000005160 1H NMR spectroscopy Methods 0.000 description 104
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 50
235000019439 ethyl acetate Nutrition 0.000 description 45
239000000243 solution Substances 0.000 description 44
238000010586 diagram Methods 0.000 description 40
239000002585 base Substances 0.000 description 35
238000006243 chemical reaction Methods 0.000 description 35
150000002475 indoles Chemical class 0.000 description 33
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 33
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 26
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
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239000007787 solid Substances 0.000 description 24
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125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 21
ZFRKQXVRDFCRJG-UHFFFAOYSA-N skatole Chemical class C1=CC=C2C(C)=CNC2=C1 ZFRKQXVRDFCRJG-UHFFFAOYSA-N 0.000 description 21
238000005406 washing Methods 0.000 description 21
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 20
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ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 16
229940074386 skatole Drugs 0.000 description 16
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
210000000988 bone and bone Anatomy 0.000 description 15
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 15
229910052794 bromium Inorganic materials 0.000 description 15
239000011541 reaction mixture Substances 0.000 description 14
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical class C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 13
238000012545 processing Methods 0.000 description 13
HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 12
239000002994 raw material Substances 0.000 description 12
238000003756 stirring Methods 0.000 description 12
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 10
229960005309 estradiol Drugs 0.000 description 10
239000006260 foam Substances 0.000 description 10
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 9
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 9
239000002253 acid Substances 0.000 description 9
239000003610 charcoal Substances 0.000 description 9
238000002474 experimental method Methods 0.000 description 9
150000003053 piperidines Chemical class 0.000 description 9
238000002360 preparation method Methods 0.000 description 9
239000000741 silica gel Substances 0.000 description 9
229910002027 silica gel Inorganic materials 0.000 description 9
150000001412 amines Chemical class 0.000 description 8
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 7
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 7
239000003981 vehicle Substances 0.000 description 7
UFZKWTITXBRSPK-UHFFFAOYSA-N (4-phenylmethoxyphenyl)hydrazine Chemical compound C1=CC(NN)=CC=C1OCC1=CC=CC=C1 UFZKWTITXBRSPK-UHFFFAOYSA-N 0.000 description 6
WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 description 6
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
102000002260 Alkaline Phosphatase Human genes 0.000 description 6
108020004774 Alkaline Phosphatase Proteins 0.000 description 6
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical group O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 6
108091008039 hormone receptors Proteins 0.000 description 6
239000007788 liquid Substances 0.000 description 6
239000000463 material Substances 0.000 description 6
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 6
239000002904 solvent Substances 0.000 description 6
CHIFTAQVXHNVRW-UHFFFAOYSA-N 1h-indole-3-carbonitrile Chemical compound C1=CC=C2C(C#N)=CNC2=C1 CHIFTAQVXHNVRW-UHFFFAOYSA-N 0.000 description 5
229920002307 Dextran Polymers 0.000 description 5
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108060001084 Luciferase Proteins 0.000 description 5
239000003513 alkali Substances 0.000 description 5
KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 5
230000008859 change Effects 0.000 description 5
239000003795 chemical substances by application Substances 0.000 description 5
235000012000 cholesterol Nutrition 0.000 description 5
239000012141 concentrate Substances 0.000 description 5
210000000172 cytosol Anatomy 0.000 description 5
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150000002576 ketones Chemical class 0.000 description 5
239000002243 precursor Substances 0.000 description 5
238000011160 research Methods 0.000 description 5
239000012266 salt solution Substances 0.000 description 5
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229960001603 tamoxifen Drugs 0.000 description 5
238000004809 thin layer chromatography Methods 0.000 description 5
210000001519 tissue Anatomy 0.000 description 5
MKYMYZJJFMPDOA-UHFFFAOYSA-N 1-(4-phenylmethoxyphenyl)ethanone Chemical compound C1=CC(C(=O)C)=CC=C1OCC1=CC=CC=C1 MKYMYZJJFMPDOA-UHFFFAOYSA-N 0.000 description 4
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 4
DNXHEGUUPJUMQT-CBZIJGRNSA-N Estrone Chemical compound OC1=CC=C2[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1 DNXHEGUUPJUMQT-CBZIJGRNSA-N 0.000 description 4
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
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241001465754 Metazoa Species 0.000 description 4
JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 4
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
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125000003282 alkyl amino group Chemical group 0.000 description 4
230000015572 biosynthetic process Effects 0.000 description 4
125000001309 chloro group Chemical group Cl* 0.000 description 4
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MGNZXYYWBUKAII-UHFFFAOYSA-N cyclohexa-1,3-diene Chemical compound C1CC=CC=C1 MGNZXYYWBUKAII-UHFFFAOYSA-N 0.000 description 4
238000003810 ethyl acetate extraction Methods 0.000 description 4
238000001914 filtration Methods 0.000 description 4
238000010438 heat treatment Methods 0.000 description 4
VKYKSIONXSXAKP-UHFFFAOYSA-N hexamethylenetetramine Chemical compound C1N(C2)CN3CN1CN2C3 VKYKSIONXSXAKP-UHFFFAOYSA-N 0.000 description 4
230000003054 hormonal effect Effects 0.000 description 4
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
GZUITABIAKMVPG-UHFFFAOYSA-N raloxifene Chemical compound C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 GZUITABIAKMVPG-UHFFFAOYSA-N 0.000 description 4
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Classifications

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- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
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- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
- A61P5/32—Antioestrogens
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/12—Radicals substituted by oxygen atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links

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Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Bioinformatics & Cheminformatics (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Engineering & Computer Science (AREA)
Endocrinology (AREA)
Physical Education & Sports Medicine (AREA)
Diabetes (AREA)
Urology & Nephrology (AREA)
Reproductive Health (AREA)
Orthopedic Medicine & Surgery (AREA)
Heart & Thoracic Surgery (AREA)
Rheumatology (AREA)
Cardiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Indole Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

CN97113496A 1996-04-19 1997-04-18 雌性激素剂 Expired - Lifetime CN1106383C (zh)

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
US63397496A	1996-04-19	1996-04-19
US633974		1996-04-19
US08/833,271 US5998402A (en)	1996-04-19	1997-04-04	2-phenyl-1-[4-(2-aminoethoxy)-benzyl]-indoles as estrogenic agents
US833271		1997-04-04

Publications (2)

Publication Number	Publication Date
CN1170719A CN1170719A (zh)	1998-01-21
CN1106383C true CN1106383C (zh)	2003-04-23

Family

ID=27092026

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CN97113496A Expired - Lifetime CN1106383C (zh)	1996-04-19	1997-04-18	雌性激素剂

Country Status (26)

Country	Link
EP (1)	EP0802183B1 (2)
JP (1)	JP4093611B2 (2)
KR (1)	KR100480193B1 (2)
CN (1)	CN1106383C (2)
AR (1)	AR011503A1 (2)
AT (1)	ATE206701T1 (2)
AU (1)	AU710149B2 (2)
BR (1)	BRPI9715334B8 (2)
CO (1)	CO4900051A1 (2)
CY (2)	CY2325B1 (2)
CZ (1)	CZ291701B6 (2)
DE (2)	DE69707189T2 (2)
DK (1)	DK0802183T3 (2)
EA (1)	EA001448B1 (2)
ES (1)	ES2162198T3 (2)
FR (1)	FR09C0048I2 (2)
HU (1)	HU227077B1 (2)
IL (1)	IL120701A (2)
LU (1)	LU91608I2 (2)
MX (1)	MX9702865A (2)
NL (1)	NL300416I2 (2)
NO (2)	NO309564B1 (2)
NZ (1)	NZ314601A (2)
PT (1)	PT802183E (2)
SK (1)	SK281737B6 (2)
UA (1)	UA48148C2 (2)

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1997
- 1997-04-15 DE DE69707189T patent/DE69707189T2/de not_active Expired - Lifetime
- 1997-04-15 NZ NZ314601A patent/NZ314601A/en not_active IP Right Cessation
- 1997-04-15 AT AT97302576T patent/ATE206701T1/de active
- 1997-04-15 DE DE122009000061C patent/DE122009000061I1/de active Pending
- 1997-04-15 ES ES97302576T patent/ES2162198T3/es not_active Expired - Lifetime
- 1997-04-15 EP EP97302576A patent/EP0802183B1/en not_active Expired - Lifetime
- 1997-04-15 DK DK97302576T patent/DK0802183T3/da active
- 1997-04-15 PT PT97302576T patent/PT802183E/pt unknown
- 1997-04-15 SK SK472-97A patent/SK281737B6/sk not_active IP Right Cessation
- 1997-04-17 AU AU18920/97A patent/AU710149B2/en not_active Expired
- 1997-04-17 UA UA97041833A patent/UA48148C2/uk unknown
- 1997-04-17 CZ CZ19971175A patent/CZ291701B6/cs not_active IP Right Cessation
- 1997-04-18 AR ARP970101580A patent/AR011503A1/es active IP Right Grant
- 1997-04-18 HU HU9700777A patent/HU227077B1/hu active Protection Beyond IP Right Term
- 1997-04-18 MX MX9702865A patent/MX9702865A/es unknown
- 1997-04-18 CN CN97113496A patent/CN1106383C/zh not_active Expired - Lifetime
- 1997-04-18 JP JP10156397A patent/JP4093611B2/ja not_active Expired - Lifetime
- 1997-04-18 IL IL12070197A patent/IL120701A/xx active Protection Beyond IP Right Term
- 1997-04-18 EA EA199700044A patent/EA001448B1/ru not_active IP Right Cessation
- 1997-04-18 KR KR1019970014894A patent/KR100480193B1/ko not_active Expired - Lifetime
- 1997-04-18 NO NO971815A patent/NO309564B1/no not_active IP Right Cessation
- 1997-04-18 CO CO97020584A patent/CO4900051A1/es unknown
- 1997-04-22 BR BRPI9715334A patent/BRPI9715334B8/pt not_active IP Right Cessation
2003
- 2003-04-08 CY CY0300038A patent/CY2325B1/xx unknown
2009
- 2009-09-23 LU LU91608C patent/LU91608I2/fr unknown
- 2009-09-28 NL NL300416C patent/NL300416I2/nl unknown
- 2009-09-30 CY CY2009016C patent/CY2009016I2/el unknown
- 2009-09-30 FR FR09C0048C patent/FR09C0048I2/fr active Active
- 2009-11-09 NO NO2009025C patent/NO2009025I2/no unknown

Also Published As

Publication number	Publication date
AU1892097A (en)	1997-10-23
FR09C0048I2 (2)	2010-06-11
CN1170719A (zh)	1998-01-21
CY2325B1 (en)	2003-11-14
DE69707189D1 (de)	2001-11-15
SK47297A3 (en)	1997-11-05
DE69707189T2 (de)	2002-06-20
MX9702865A (es)	1998-05-31
HUP9700777A2 (hu)	1999-06-28
AR011503A1 (es)	2000-08-30
SK281737B6 (sk)	2001-07-10
ES2162198T3 (es)	2001-12-16
IL120701A (en)	2005-09-25
NL300416I1 (nl)	2009-12-01
BRPI9715334B8 (pt)	2021-05-25
EA001448B1 (ru)	2001-04-23
NO971815L (no)	1997-10-20
JP4093611B2 (ja)	2008-06-04
IL120701A0 (en)	1997-09-30
AU710149B2 (en)	1999-09-16
NO2009025I2 (no)	2010-11-22
EP0802183B1 (en)	2001-10-10
CO4900051A1 (es)	2000-03-27
NO2009025I1 (no)	2009-11-30
CY2009016I1 (el)	2010-07-28
FR09C0048I1 (2)	2009-06-11
ATE206701T1 (de)	2001-10-15
DK0802183T3 (da)	2002-02-04
EP0802183A1 (en)	1997-10-22
UA48148C2 (uk)	2002-08-15
JPH1036346A (ja)	1998-02-10
PT802183E (pt)	2002-03-28
KR970069037A (ko)	1997-11-07
HU227077B1 (en)	2010-06-28
LU91608I2 (fr)	2009-11-23
HU9700777D0 (en)	1997-06-30
NZ314601A (en)	1999-09-29
HUP9700777A3 (en)	2000-04-28
NO309564B1 (no)	2001-02-19
NL300416I2 (nl)	2010-02-01
CY2009016I2 (el)	2010-07-28
DE122009000061I1 (de)	2009-12-31
NO971815D0 (no)	1997-04-18
BR9715334B1 (pt)	2012-09-04
CZ291701B6 (cs)	2003-05-14
KR100480193B1 (ko)	2005-08-30
HK1002863A1 (en)	1998-09-25
CZ117597A3 (en)	1997-11-12
EA199700044A1 (ru)	1997-12-30

Legal Events

Date	Code	Title	Description
1998-01-21	C06	Publication
1998-01-21	PB01	Publication
1999-05-05	C10	Entry into substantive examination
1999-05-05	SE01	Entry into force of request for substantive examination
2003-04-23	C14	Grant of patent or utility model
2003-04-23	GR01	Patent grant
2003-08-20	C56	Change in the name or address of the patentee	Owner name: WYETH CORP. Free format text: FORMER NAME OR ADDRESS: AMERICAN HOME PRODUCTS CORP.
2003-08-20	CP01	Change in the name or title of a patent holder	Patentee after: Wyeth Corp. Patentee before: American Home Products Corp.
2017-05-24	CX01	Expiry of patent term
2017-05-24	CX01	Expiry of patent term	Granted publication date: 20030423

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