AU2009246348B2 - Tetrahydrocyclopenta[b]indole androgen receptor modulators - Google Patents
Tetrahydrocyclopenta[b]indole androgen receptor modulators Download PDFInfo
- Publication number
- AU2009246348B2 AU2009246348B2 AU2009246348A AU2009246348A AU2009246348B2 AU 2009246348 B2 AU2009246348 B2 AU 2009246348B2 AU 2009246348 A AU2009246348 A AU 2009246348A AU 2009246348 A AU2009246348 A AU 2009246348A AU 2009246348 B2 AU2009246348 B2 AU 2009246348B2
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- IAZKTAKWBHQCGF-UHFFFAOYSA-N 1,2,3,3a-tetrahydrocyclopenta[b]indole Chemical compound N1=C2C=CC=CC2=C2C1CCC2 IAZKTAKWBHQCGF-UHFFFAOYSA-N 0.000 title description 11
- 239000000849 selective androgen receptor modulator Substances 0.000 title description 8
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- FBCDRHDULQYRTB-UHFFFAOYSA-N 2-[2-ethoxy-5-(4-ethylpiperazin-1-yl)sulfonylphenyl]-5-methyl-7-propyl-1h-imidazo[5,1-f][1,2,4]triazin-4-one;trihydrate;hydrochloride Chemical compound O.O.O.Cl.CCCC1=NC(C)=C(C(N=2)=O)N1NC=2C(C(=CC=1)OCC)=CC=1S(=O)(=O)N1CCN(CC)CC1 FBCDRHDULQYRTB-UHFFFAOYSA-N 0.000 claims description 5
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- HNKVROGLZCBJBV-KRWDZBQOSA-N propan-2-yl n-[(2s)-7-cyano-4-[(2-hydroxyphenyl)methyl]-2,3-dihydro-1h-cyclopenta[b]indol-2-yl]carbamate Chemical compound C([C@H](C1)NC(=O)OC(C)C)C2=C1C1=CC(C#N)=CC=C1N2CC1=CC=CC=C1O HNKVROGLZCBJBV-KRWDZBQOSA-N 0.000 claims description 3
- RUXJDAYOICLRHH-INIZCTEOSA-N propan-2-yl n-[(2s)-7-cyano-4-[(3-fluoro-2-hydroxyphenyl)methyl]-2,3-dihydro-1h-cyclopenta[b]indol-2-yl]carbamate Chemical compound C([C@H](C1)NC(=O)OC(C)C)C2=C1C1=CC(C#N)=CC=C1N2CC1=CC=CC(F)=C1O RUXJDAYOICLRHH-INIZCTEOSA-N 0.000 claims description 2
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- PFYFLKXRXBSBLG-UHFFFAOYSA-N pyrrolidin-1-yl 2-chloroacetate Chemical compound ClCC(=O)ON1CCCC1 PFYFLKXRXBSBLG-UHFFFAOYSA-N 0.000 description 1
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- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 1
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- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
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- 239000011780 sodium chloride Substances 0.000 description 1
- 239000011684 sodium molybdate Substances 0.000 description 1
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- TVXXNOYZHKPKGW-UHFFFAOYSA-N sodium molybdate (anhydrous) Chemical compound [Na+].[Na+].[O-][Mo]([O-])(=O)=O TVXXNOYZHKPKGW-UHFFFAOYSA-N 0.000 description 1
- 241000894007 species Species 0.000 description 1
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- 238000004808 supercritical fluid chromatography Methods 0.000 description 1
- 238000004885 tandem mass spectrometry Methods 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- LAZGNUQPARJCNT-NTUVXCKYSA-N tert-butyl (2r,3r)-3-(2-chloroacetyl)oxy-2-[[(2s)-7-cyano-2-(propan-2-yloxycarbonylamino)-2,3-dihydro-1h-cyclopenta[b]indol-4-yl]methyl]pyrrolidine-1-carboxylate Chemical compound C([C@H](C1)NC(=O)OC(C)C)C2=C1C1=CC(C#N)=CC=C1N2C[C@@H]1[C@H](OC(=O)CCl)CCN1C(=O)OC(C)(C)C LAZGNUQPARJCNT-NTUVXCKYSA-N 0.000 description 1
- JQXFBJIDTLTFNU-UHFFFAOYSA-N tert-butyl 3-methylpyrrolidine-1-carboxylate Chemical compound CC1CCN(C(=O)OC(C)(C)C)C1 JQXFBJIDTLTFNU-UHFFFAOYSA-N 0.000 description 1
- UOUFRTFWWBCVPV-UHFFFAOYSA-N tert-butyl 4-(2,4-dioxo-1H-thieno[3,2-d]pyrimidin-3-yl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(CC1)n1c(=O)[nH]c2ccsc2c1=O UOUFRTFWWBCVPV-UHFFFAOYSA-N 0.000 description 1
- LPQZERIRKRYGGM-UHFFFAOYSA-N tert-butyl pyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCC1 LPQZERIRKRYGGM-UHFFFAOYSA-N 0.000 description 1
- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 1
- SKWXBTTYZWGUGQ-UHFFFAOYSA-N tert-butyl-(4-fluoro-2-methylphenoxy)-dimethylsilane Chemical compound CC1=CC(F)=CC=C1O[Si](C)(C)C(C)(C)C SKWXBTTYZWGUGQ-UHFFFAOYSA-N 0.000 description 1
- PFBFNQGTNWUPHQ-UHFFFAOYSA-N tert-butyl-[(4-fluoro-2-methylphenyl)methyl]-dimethylsilane Chemical compound CC1=CC(F)=CC=C1C[Si](C)(C)C(C)(C)C PFBFNQGTNWUPHQ-UHFFFAOYSA-N 0.000 description 1
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- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 1
- 239000012096 transfection reagent Substances 0.000 description 1
- 229940094720 viagra Drugs 0.000 description 1
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- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
- SRWMQSFFRFWREA-UHFFFAOYSA-M zinc formate Chemical compound [Zn+2].[O-]C=O SRWMQSFFRFWREA-UHFFFAOYSA-M 0.000 description 1
Classifications
-
- 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
- C07D209/56—Ring systems containing three or more rings
- C07D209/80—[b, c]- or [b, d]-condensed
- C07D209/94—[b, c]- or [b, d]-condensed containing carbocyclic rings other than six-membered
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/06—Anabolic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
- A61P5/26—Androgens
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
- C07D403/06—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 carbon chain containing only aliphatic carbon atoms
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (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)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Physical Education & Sports Medicine (AREA)
- Endocrinology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- Diabetes (AREA)
- Neurology (AREA)
- Reproductive Health (AREA)
- Gynecology & Obstetrics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US5372208P | 2008-05-16 | 2008-05-16 | |
| US61/053,722 | 2008-05-16 | ||
| PCT/US2009/043875 WO2009140448A1 (en) | 2008-05-16 | 2009-05-14 | Tetrahydrocyclopenta[b]indole androgen receptor modulators |
Publications (3)
| Publication Number | Publication Date |
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| AU2009246348A1 AU2009246348A1 (en) | 2009-11-19 |
| AU2009246348A8 AU2009246348A8 (en) | 2010-12-16 |
| AU2009246348B2 true AU2009246348B2 (en) | 2012-04-12 |
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| AU2009246348A Ceased AU2009246348B2 (en) | 2008-05-16 | 2009-05-14 | Tetrahydrocyclopenta[b]indole androgen receptor modulators |
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| BR (1) | BRPI0912394A2 (enExample) |
| CA (1) | CA2724629C (enExample) |
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| HR (1) | HRP20120917T1 (enExample) |
| MX (1) | MX2010012436A (enExample) |
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| PT (1) | PT2297100E (enExample) |
| SI (1) | SI2297100T1 (enExample) |
| WO (1) | WO2009140448A1 (enExample) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| UA98777C2 (en) | 2006-11-20 | 2012-06-25 | Эли Лилли Энд Компани | Tetrahydrocyclopenta[b]indole compounds as androgen receptor modulators |
| US8268872B2 (en) | 2008-02-22 | 2012-09-18 | Radius Health, Inc. | Selective androgen receptor modulators |
| BRPI0907844B8 (pt) | 2008-02-22 | 2021-05-25 | Radius Health Inc | compostos e método para modular um receptor de andrógeno, processos de preparação e composição farmacêutica dos mesmos e seus usos |
| US8987319B2 (en) | 2010-02-04 | 2015-03-24 | Radius Health, Inc. | Selective androgen receptor modulators |
| PT2568806T (pt) | 2010-05-12 | 2016-08-05 | Radius Health Inc | Regimes terapêuticos |
| US8642632B2 (en) | 2010-07-02 | 2014-02-04 | Radius Health, Inc. | Selective androgen receptor modulators |
| WO2012047617A1 (en) | 2010-09-28 | 2012-04-12 | Radius Health, Inc. | Selective androgen receptor modulators |
| US9421264B2 (en) | 2014-03-28 | 2016-08-23 | Duke University | Method of treating cancer using selective estrogen receptor modulators |
| PL3122426T3 (pl) | 2014-03-28 | 2023-05-15 | Duke University | Leczenie raka sutka z zastosowaniem selektywnych modulatorów receptora estrogenowego |
| JOP20180072A1 (ar) * | 2014-09-11 | 2019-01-30 | Lilly Co Eli | علاج الأعراض المرتبطة بالعلاج بالحرمان من الأندروجين |
| SMT202200199T1 (it) | 2016-06-22 | 2022-07-21 | Ellipses Pharma Ltd | Metodi di trattamento del cancro del seno ar+. |
| US20180185347A1 (en) * | 2016-11-16 | 2018-07-05 | Transition Therapeutics (Ireland 2) Limited | Tetrahydrocyclopenta[b]indole compounds and phosphodiesterase inhibitors for the treatment of the signs and symptoms of bhp |
| EP4374925A3 (en) | 2017-01-05 | 2025-01-15 | Radius Pharmaceuticals, Inc. | Polymorphic forms of rad1901-2hcl |
| CN112423844B (zh) | 2018-07-04 | 2024-08-13 | 雷迪厄斯制药公司 | Rad1901-2hcl的多晶型形式 |
| CN119390714A (zh) | 2019-02-12 | 2025-02-07 | 雷迪厄斯制药公司 | 方法和化合物 |
| EP4096660A1 (en) * | 2020-01-27 | 2022-12-07 | EirGen Pharma Ltd. | Tetrahydrocyclopenta[b]indole compounds for the treatment of renal disease |
| EP4175647A4 (en) * | 2020-07-06 | 2024-08-07 | Crescenta Biosciences | ANTIVIRAL USE OF COMPOUNDS MODULATING FABP4 |
Citations (1)
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| WO2008063867A2 (en) * | 2006-11-20 | 2008-05-29 | Eli Lilly And Company | Tetrahydrocyclopenta[b] indole compounds as androgen receptor modulators |
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| US4988820A (en) | 1986-02-21 | 1991-01-29 | Bayer Aktiengesellschaft | Cycloalkano(1,2-B) indole-sulponamides |
| GB8924392D0 (en) | 1989-10-30 | 1989-12-20 | Bayer Ag | Substituted cycloalkano/b/dihydroindole-and-indolesulphonamides |
| GB9008108D0 (en) | 1990-04-10 | 1990-06-06 | Bayer Ag | Cycloalkano(b)dihydroindoles and-indolesulphonamides substituted by heterocycles |
| DE4027278A1 (de) | 1990-08-29 | 1992-03-05 | Bayer Ag | Heterocyclisch substituierte indolsulfonamide |
| DE4131346A1 (de) | 1991-09-20 | 1993-03-25 | Bayer Ag | Indolsulfonamid substituierte dihydropyridine, verfahren zu ihrer herstellung und ihre verwendung in arzneimitteln |
| US7160909B2 (en) | 2001-08-09 | 2007-01-09 | Eli Lilly And Company | Cyclopenta[b]indole derivatives as sPLA2 inhibitors |
| DE10164564B4 (de) | 2001-12-14 | 2007-05-16 | Zentaris Gmbh | Tetrahydrocarbazolderivate als Liganden für G-Protein gekoppelte Rezeptoren (GPCR) |
| US7534897B2 (en) | 2002-05-16 | 2009-05-19 | Shionogi & Co., Ltd. | Indole arylsulfonaimide compounds exhibiting PGD 2 receptor antagonism |
| US20060074124A1 (en) | 2003-09-12 | 2006-04-06 | Andrew Napper | Methods of treating a disorder |
| US7019022B2 (en) | 2003-12-15 | 2006-03-28 | Merck Frosst Canada & Co. | Substituted tetrahydrocarbazole and cyclopentanoindole derivatives |
| EP1723105B1 (en) | 2004-03-03 | 2013-05-15 | Eli Lilly And Company | Bicyclic substituted indole-derivative steroid hormone nuclear receptor modulators |
| JP2008520742A (ja) | 2004-11-23 | 2008-06-19 | ピーティーシー セラピューティクス， インコーポレイテッド | Ｖｅｇｆ産生の阻害に有用なカルバゾール誘導体、カルボリン誘導体およびインドール誘導体 |
| EP1856126A2 (en) * | 2005-02-17 | 2007-11-21 | Wyeth a Corporation of the State of Delaware | Cycloalkylfused indole, benzothiophene, benzofuran and indene derivatives |
| JP5204650B2 (ja) | 2005-06-24 | 2013-06-05 | イーライ リリー アンド カンパニー | アンドロゲン受容体調節物質として有用なテトラヒドロカルバゾール誘導体 |
| US20090022694A1 (en) | 2005-10-18 | 2009-01-22 | Distefano Peter | Sirt1 inhibition |
| WO2008019825A1 (en) | 2006-08-14 | 2008-02-21 | Santhera Pharmaceuticals (Schweiz) Ag | Use of tricyclic indole derivatives for the treatment of muscular diseases |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2008063867A2 (en) * | 2006-11-20 | 2008-05-29 | Eli Lilly And Company | Tetrahydrocyclopenta[b] indole compounds as androgen receptor modulators |
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| JP2011520903A (ja) | 2011-07-21 |
| HRP20120917T1 (hr) | 2012-12-31 |
| AU2009246348A8 (en) | 2010-12-16 |
| EP2297100A1 (en) | 2011-03-23 |
| WO2009140448A1 (en) | 2009-11-19 |
| CN102026974A (zh) | 2011-04-20 |
| SI2297100T1 (sl) | 2013-02-28 |
| CA2724629A1 (en) | 2009-11-19 |
| ES2396612T3 (es) | 2013-02-22 |
| EP2297100B1 (en) | 2012-10-31 |
| AU2009246348A1 (en) | 2009-11-19 |
| KR20100132551A (ko) | 2010-12-17 |
| JP5603327B2 (ja) | 2014-10-08 |
| US8486943B2 (en) | 2013-07-16 |
| PL2297100T3 (pl) | 2013-03-29 |
| CA2724629C (en) | 2014-08-19 |
| MX2010012436A (es) | 2010-12-06 |
| PT2297100E (pt) | 2013-01-24 |
| CY1113341T1 (el) | 2016-06-22 |
| KR101278788B1 (ko) | 2013-06-25 |
| EA201071317A1 (ru) | 2011-06-30 |
| BRPI0912394A2 (pt) | 2016-07-26 |
| CN102026974B (zh) | 2013-08-28 |
| DK2297100T3 (da) | 2012-12-17 |
| WO2009140448A8 (en) | 2010-01-07 |
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Free format text: IN VOL 24, NO 46, PAGE(S) 5274 UNDER THE HEADING PCT APPLICATIONS THAT HAVE ENTERED THE NATIONAL PHASE - NAME INDEX UNDER THE NAME ELI LILLY AND COMPANY, APPLICATION NO. 2009246348, UNDER INID (54) CORRECT THE TITLE TO READ TETRAHYDROCYCLOPENTA¢B!INDOLE ANDROGEN RECEPTOR MODULATORS. |
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| MK14 | Patent ceased section 143(a) (annual fees not paid) or expired |