HK1074592A1 - 17 beta-hydroxysteroid dehydrogenase type 3 inhibitors for the treatment of androgen dependent diseases - Google Patents
17 beta-hydroxysteroid dehydrogenase type 3 inhibitors for the treatment of androgen dependent diseasesInfo
- Publication number
- HK1074592A1 HK1074592A1 HK05108331A HK05108331A HK1074592A1 HK 1074592 A1 HK1074592 A1 HK 1074592A1 HK 05108331 A HK05108331 A HK 05108331A HK 05108331 A HK05108331 A HK 05108331A HK 1074592 A1 HK1074592 A1 HK 1074592A1
- Authority
- HK
- Hong Kong
- Prior art keywords
- hydroxysteroid dehydrogenase
- inhibitors
- treatment
- beta
- compounds
- Prior art date
Links
Classifications
-
- 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
- C07D401/14—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 three or more hetero rings
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/08—Drugs for disorders of the urinary system of the prostate
-
- 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
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/08—Antiseborrheics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/10—Anti-acne agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/14—Drugs for dermatological disorders for baldness or alopecia
-
- 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
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- 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
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
- A61P5/28—Antiandrogens
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/10—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms
- C07D211/16—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms with acylated ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/04—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/06—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having one or two double bonds between ring members or between ring members and non-ring members
- C07D241/08—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having one or two double bonds between ring members or between ring members and non-ring members with oxygen atoms directly attached to ring carbon atoms
-
- 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
- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Dermatology (AREA)
- Reproductive Health (AREA)
- Endocrinology (AREA)
- Oncology (AREA)
- Diabetes (AREA)
- Urology & Nephrology (AREA)
- Gynecology & Obstetrics (AREA)
- Pregnancy & Childbirth (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Steroid Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US43410102P | 2002-12-17 | 2002-12-17 | |
| PCT/US2003/039863 WO2004060488A1 (en) | 2002-12-17 | 2003-12-15 | 17 beta-hydroxysteroid dehydrogenase type 3 inhibitors for the treatment of androgen dependent diseases |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HK1074592A1 true HK1074592A1 (en) | 2005-11-18 |
Family
ID=32713010
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HK05108331A HK1074592A1 (en) | 2002-12-17 | 2005-09-22 | 17 beta-hydroxysteroid dehydrogenase type 3 inhibitors for the treatment of androgen dependent diseases |
Country Status (12)
| Country | Link |
|---|---|
| US (3) | US7053091B2 (xx) |
| EP (1) | EP1572299B1 (xx) |
| JP (1) | JP4585320B2 (xx) |
| CN (1) | CN1744930A (xx) |
| AT (1) | ATE409065T1 (xx) |
| AU (1) | AU2003293555A1 (xx) |
| CA (1) | CA2509758A1 (xx) |
| DE (1) | DE60323765D1 (xx) |
| ES (1) | ES2312845T3 (xx) |
| HK (1) | HK1074592A1 (xx) |
| MX (1) | MXPA05006485A (xx) |
| WO (1) | WO2004060488A1 (xx) |
Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2509758A1 (en) * | 2002-12-17 | 2004-07-22 | Schering Corporation | 17 beta-hydroxysteroid dehydrogenase type 3 inhibitors for the treatment of androgen dependent diseases |
| BRPI0509803A (pt) * | 2004-04-13 | 2007-09-18 | Incyte Corp | derivados de piperazinilpiperidina como antagonistas de receptor de quimiocina |
| US7598259B2 (en) * | 2004-06-15 | 2009-10-06 | Schering Corporation | mGluR1 antagonists as therapeutic agents |
| JP4091095B2 (ja) * | 2004-08-06 | 2008-05-28 | シャープ株式会社 | 送信機、受信機、通信システム、通信方法、通信プログラム |
| JP2008537940A (ja) | 2005-03-29 | 2008-10-02 | ザ・トラスティーズ・オブ・ザ・ユニバーシティ・オブ・ペンシルバニア | 新しい毛包の形成、はげ頭症の治療、及び除毛をするための方法 |
| GB0513702D0 (en) * | 2005-07-04 | 2005-08-10 | Sterix Ltd | Compound |
| US20070197590A1 (en) * | 2006-01-31 | 2007-08-23 | Demong Duane E | Substituted dipiperidine ccr2 antagonists |
| US20080051380A1 (en) | 2006-08-25 | 2008-02-28 | Auerbach Alan H | Methods and compositions for treating cancer |
| US8080540B2 (en) | 2006-09-19 | 2011-12-20 | Abbott Products Gmbh | Therapeutically active triazoles and their use |
| US8288367B2 (en) | 2006-11-30 | 2012-10-16 | Solvay Pharmaceuticals Gmbh | Substituted estratriene derivatives as 17BETA HSD inhibitors |
| KR20120027177A (ko) * | 2009-04-02 | 2012-03-21 | 메르크 파텐트 게엠베하 | 오토탁신 저해제로서의 피페리딘 및 피라진 유도체 |
| BR112013014021A8 (pt) | 2010-12-06 | 2017-10-03 | Follica Inc | Métodos para tratamento de calvície e promoção de crescimento de cabelos |
| WO2014207309A1 (en) | 2013-06-25 | 2014-12-31 | Forendo Pharma Ltd | Therapeutically active estratrienthiazole derivatives as inhibitors of 17 b-hydroxysteroid dehydrogenase, type 1 |
| CN105518015B (zh) | 2013-06-25 | 2017-09-15 | 佛恩多制药有限公司 | 治疗活性的作为17β‑羟基类固醇脱氢酶抑制剂的17‑氮取代雌三烯噻唑衍生物 |
| TW201522359A (zh) | 2013-06-25 | 2015-06-16 | Forendo Pharma Ltd | 治療用活性雌三烯噻唑衍生物 |
| DE102014005129A1 (de) | 2014-04-08 | 2014-11-06 | Daimler Ag | Verfahren und Fahrerassistenzvorrichtung zur Unterstützung eines Fahrers beim Führen eines Fahrzeugs |
| JP6523461B2 (ja) | 2014-12-23 | 2019-06-05 | フォレンド ファーマ リミテッド | １７β−ＨＳＤ１−阻害剤のプロドラッグ |
| US10626140B2 (en) | 2014-12-23 | 2020-04-21 | Forendo Pharma Ltd | Prodrugs of 17β-HSD1-inhibitors |
| CN105461705B (zh) * | 2015-11-30 | 2018-04-10 | 中国医科大学 | 二苯并氮杂卓二酮类抗肿瘤化合物及其制备方法 |
| JP2019522032A (ja) | 2016-07-29 | 2019-08-08 | ヤンセン ファーマシューティカ エヌ．ベー． | 前立腺癌の治療方法 |
| HUE066375T2 (hu) | 2017-06-08 | 2024-07-28 | Organon R&D Finland Ltd | A 15.béta.-[3-propanamido]-szubsztituált estra-1,3,5(10)-trien-17-one 17-oximjai a 17.béta.-hidroxiszteroid-dehidrogenázok gátlásában való felhasználásra |
| CA3122049C (en) | 2018-12-05 | 2023-10-17 | Forendo Pharma Ltd | Estra-1,3,5(10)-triene compounds condensed in position 16(17) with a pyrazole ring as inhibitors of 17-hsd1 |
| CN112321515A (zh) * | 2020-10-21 | 2021-02-05 | 上海馨远医药科技有限公司 | 一种手性1-叔丁基-3-甲基-6-甲基哌嗪-1,3-二甲酸酯的制备方法 |
| CN112321538A (zh) * | 2020-10-28 | 2021-02-05 | 都创(上海)医药开发有限公司 | 一种合成单胺保护的哌嗪-（r/s）2-甲酸酯的方法 |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IE58836B1 (en) | 1984-08-02 | 1993-11-17 | Labrie Fernand | Pharmaceutical composition for combination therapy of hormone dependent cancers |
| WO1990010462A1 (en) | 1989-03-10 | 1990-09-20 | Endorecherche Inc. | Combination therapy for treatment of estrogen sensitive diseases |
| DK0943328T3 (da) | 1989-07-07 | 2004-10-18 | Endorech Inc | Kombinationsterapi til profylakse og/eller behandling af godartet prostatahyperplasi |
| ES2189784T3 (es) | 1989-07-07 | 2003-07-16 | Endorech Inc | Procedimiento para el tratamiento de enfermedades relacionadas con adrogenos. |
| US6060503A (en) | 1991-12-02 | 2000-05-09 | Endorecherche, Inc. | Benzopyran-containing compounds and method for their use |
| PL307333A1 (en) | 1993-05-17 | 1995-05-15 | Endorecherche Inc | Improved antiandrogens |
| US6124115A (en) | 1995-09-22 | 2000-09-26 | Endorecherche Inc. | Production and use of isolated type 5 17β-hydroxysteroid dehydrogenase |
| US6162804A (en) * | 1997-09-26 | 2000-12-19 | Merck & Co., Inc. | Tyrosine kinase inhibitors |
| CN1429104A (zh) | 1998-03-11 | 2003-07-09 | 内部研究股份有限公司 | 5型和3型17β－羟基类固醇脱氢酶的抑制剂及其用法 |
| AU754529B2 (en) | 1998-09-22 | 2002-11-21 | Yamanouchi Pharmaceutical Co., Ltd. | Cyanophenyl derivatives |
| JP2002533335A (ja) * | 1998-12-18 | 2002-10-08 | シェーリング コーポレイション | ファルネシルタンパク質トランスフェラーゼインヒビター |
| US6362188B1 (en) * | 1998-12-18 | 2002-03-26 | Schering Corporation | Farnesyl protein transferase inhibitors |
| PE20030703A1 (es) * | 2001-09-06 | 2003-08-21 | Schering Corp | Inhibidores de la 17b-hidroxiesteroide deshidrogenasa tipo 3 |
| CA2463626C (en) * | 2001-10-17 | 2011-05-24 | Schering Corporation | Piperidine- and piperazineacetamines as 17beta-hydroxysteroid dehydrogenase type 3 inhibitors for the treatment of androgen dependent diseases |
| ATE469886T1 (de) | 2002-11-18 | 2010-06-15 | Schering Corp | 17beta-hydroxysteroid dehydrogenase typ-3 hemmer zur behandlung von androgen abhängigen erkrankungen |
| CA2509758A1 (en) * | 2002-12-17 | 2004-07-22 | Schering Corporation | 17 beta-hydroxysteroid dehydrogenase type 3 inhibitors for the treatment of androgen dependent diseases |
-
2003
- 2003-12-15 CA CA002509758A patent/CA2509758A1/en not_active Abandoned
- 2003-12-15 JP JP2004565490A patent/JP4585320B2/ja not_active Expired - Fee Related
- 2003-12-15 US US10/735,983 patent/US7053091B2/en not_active Expired - Fee Related
- 2003-12-15 EP EP03790505A patent/EP1572299B1/en not_active Expired - Lifetime
- 2003-12-15 WO PCT/US2003/039863 patent/WO2004060488A1/en active Application Filing
- 2003-12-15 AU AU2003293555A patent/AU2003293555A1/en not_active Abandoned
- 2003-12-15 ES ES03790505T patent/ES2312845T3/es not_active Expired - Lifetime
- 2003-12-15 CN CNA2003801094364A patent/CN1744930A/zh active Pending
- 2003-12-15 DE DE60323765T patent/DE60323765D1/de not_active Expired - Lifetime
- 2003-12-15 MX MXPA05006485A patent/MXPA05006485A/es active IP Right Grant
- 2003-12-15 AT AT03790505T patent/ATE409065T1/de not_active IP Right Cessation
-
2005
- 2005-09-22 HK HK05108331A patent/HK1074592A1/xx not_active IP Right Cessation
-
2006
- 2006-02-23 US US11/360,711 patent/US7271175B2/en not_active Expired - Fee Related
-
2007
- 2007-08-09 US US11/836,530 patent/US7485645B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CN1744930A (zh) | 2006-03-08 |
| US20060142338A1 (en) | 2006-06-29 |
| US7485645B2 (en) | 2009-02-03 |
| EP1572299B1 (en) | 2008-09-24 |
| US7271175B2 (en) | 2007-09-18 |
| MXPA05006485A (es) | 2005-08-26 |
| US20080004248A1 (en) | 2008-01-03 |
| JP4585320B2 (ja) | 2010-11-24 |
| US20040138226A1 (en) | 2004-07-15 |
| ATE409065T1 (de) | 2008-10-15 |
| AU2003293555A1 (en) | 2004-07-29 |
| ES2312845T3 (es) | 2009-03-01 |
| CA2509758A1 (en) | 2004-07-22 |
| WO2004060488A1 (en) | 2004-07-22 |
| EP1572299A1 (en) | 2005-09-14 |
| US7053091B2 (en) | 2006-05-30 |
| JP2006514054A (ja) | 2006-04-27 |
| DE60323765D1 (de) | 2008-11-06 |
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Effective date: 20121215 |