AU2008225753A1 - Tricyclic isoquinoline derivatives for treatment of obesity - Google Patents
Tricyclic isoquinoline derivatives for treatment of obesity Download PDFInfo
- Publication number
- AU2008225753A1 AU2008225753A1 AU2008225753A AU2008225753A AU2008225753A1 AU 2008225753 A1 AU2008225753 A1 AU 2008225753A1 AU 2008225753 A AU2008225753 A AU 2008225753A AU 2008225753 A AU2008225753 A AU 2008225753A AU 2008225753 A1 AU2008225753 A1 AU 2008225753A1
- Authority
- AU
- Australia
- Prior art keywords
- tetrahydro
- azepino
- indole
- alkyl
- sulfonyl
- Prior art date
- 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.)
- Abandoned
Links
- 238000011282 treatment Methods 0.000 title claims description 16
- 208000008589 Obesity Diseases 0.000 title description 8
- 235000020824 obesity Nutrition 0.000 title description 8
- 125000002183 isoquinolinyl group Chemical class C1(=NC=CC2=CC=CC=C12)* 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims description 197
- -1 imidazolyl-methyl Chemical group 0.000 claims description 134
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 109
- 238000000034 method Methods 0.000 claims description 77
- 239000000203 mixture Substances 0.000 claims description 63
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 38
- 125000003118 aryl group Chemical group 0.000 claims description 37
- 150000003839 salts Chemical class 0.000 claims description 35
- 229910052739 hydrogen Inorganic materials 0.000 claims description 33
- 108091005435 5-HT6 receptors Proteins 0.000 claims description 32
- 239000001257 hydrogen Substances 0.000 claims description 32
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 30
- 230000037396 body weight Effects 0.000 claims description 29
- 125000001072 heteroaryl group Chemical group 0.000 claims description 24
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 23
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 22
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 22
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 20
- 229910052736 halogen Inorganic materials 0.000 claims description 20
- 150000002367 halogens Chemical class 0.000 claims description 20
- 125000001424 substituent group Chemical group 0.000 claims description 20
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 19
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 19
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 17
- 230000009467 reduction Effects 0.000 claims description 15
- DXGYZOISMWKYNC-UHFFFAOYSA-N 1H-azepino[5,4,3-cd]indole Chemical compound C1=NC=CC2=CNC3=CC=CC1=C32 DXGYZOISMWKYNC-UHFFFAOYSA-N 0.000 claims description 14
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 11
- 229910052799 carbon Inorganic materials 0.000 claims description 10
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 claims description 10
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 9
- 230000000694 effects Effects 0.000 claims description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- 238000011321 prophylaxis Methods 0.000 claims description 9
- 125000004429 atom Chemical group 0.000 claims description 8
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 8
- 150000002431 hydrogen Chemical class 0.000 claims description 8
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims description 8
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 7
- 125000001153 fluoro group Chemical group F* 0.000 claims description 7
- 235000019786 weight gain Nutrition 0.000 claims description 7
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 6
- ZUSWDTWYONAOPH-UHFFFAOYSA-N [2-(trifluoromethyl)phenyl]hydrazine;hydrochloride Chemical group [Cl-].[NH3+]NC1=CC=CC=C1C(F)(F)F ZUSWDTWYONAOPH-UHFFFAOYSA-N 0.000 claims description 6
- 125000000623 heterocyclic group Chemical group 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 230000003287 optical effect Effects 0.000 claims description 6
- 239000004031 partial agonist Substances 0.000 claims description 6
- GTTLPYDKIIPQQI-UHFFFAOYSA-N 1-(phenylsulfonyl)-1,3,4,5-tetrahydropyrrolo[4,3,2-de]isoquinoline Chemical compound C1=C(C=23)CNCC3=CC=CC=2N1S(=O)(=O)C1=CC=CC=C1 GTTLPYDKIIPQQI-UHFFFAOYSA-N 0.000 claims description 5
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 5
- 125000002883 imidazolyl group Chemical group 0.000 claims description 5
- 238000002560 therapeutic procedure Methods 0.000 claims description 5
- 125000001544 thienyl group Chemical group 0.000 claims description 5
- 125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 claims description 4
- 101100440695 Dictyostelium discoideum corB gene Proteins 0.000 claims description 4
- 239000004480 active ingredient Substances 0.000 claims description 4
- 125000000723 dihydrobenzofuranyl group Chemical group O1C(CC2=C1C=CC=C2)* 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 4
- 125000002541 furyl group Chemical group 0.000 claims description 4
- 150000004677 hydrates Chemical class 0.000 claims description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 4
- 150000003951 lactams Chemical group 0.000 claims description 4
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- 239000012453 solvate Substances 0.000 claims description 4
- 125000000335 thiazolyl group Chemical group 0.000 claims description 4
- QOEYGXNMQBQLFB-UHFFFAOYSA-N 1-(phenylsulfonyl)-3,4,5,6-tetrahydro-1h-azepino[5,4,3-cd]indol Chemical compound C1=C(C=23)CCNCC3=CC=CC=2N1S(=O)(=O)C1=CC=CC=C1 QOEYGXNMQBQLFB-UHFFFAOYSA-N 0.000 claims description 3
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 3
- 125000004104 aryloxy group Chemical group 0.000 claims description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 3
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 3
- 239000003751 serotonin 6 antagonist Substances 0.000 claims description 3
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 claims description 3
- 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 claims description 2
- 125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#N 0.000 claims description 2
- 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 claims description 2
- OGHLQPHXJWUNCN-UHFFFAOYSA-N 3-(1,2-dimethylimidazol-4-yl)sulfonyl-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13)-tetraene Chemical compound CN1C(C)=NC(S(=O)(=O)N2C=3C=CC=C4CNCCC(C=34)=C2)=C1 OGHLQPHXJWUNCN-UHFFFAOYSA-N 0.000 claims description 2
- DGJITNDIQSSJAP-UHFFFAOYSA-N 3-(benzenesulfonyl)-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13)-tetraen-12-ol Chemical compound C1=C(C2=3)C(O)CNCC2=CC=CC=3N1S(=O)(=O)C1=CC=CC=C1 DGJITNDIQSSJAP-UHFFFAOYSA-N 0.000 claims description 2
- KBYIVTOFNUFVHS-UHFFFAOYSA-N 3-(benzenesulfonyl)-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13)-tetraen-12-one Chemical compound C1=C(C2=3)C(=O)CNCC2=CC=CC=3N1S(=O)(=O)C1=CC=CC=C1 KBYIVTOFNUFVHS-UHFFFAOYSA-N 0.000 claims description 2
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 2
- XXWHMIZCYYXHBP-UHFFFAOYSA-N 3-pyridin-3-ylsulfonyl-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13)-tetraene Chemical compound C1=C(C=23)CCNCC3=CC=CC=2N1S(=O)(=O)C1=CC=CN=C1 XXWHMIZCYYXHBP-UHFFFAOYSA-N 0.000 claims description 2
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 2
- 125000001246 bromo group Chemical group Br* 0.000 claims description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
- 239000002537 cosmetic Substances 0.000 claims description 2
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims 8
- 241000124008 Mammalia Species 0.000 claims 5
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 2
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims 1
- 125000006555 (C3-C5) cycloalkyl group Chemical group 0.000 claims 1
- VFULUTRECSYTSU-UHFFFAOYSA-N 3-(2,5-dimethylthiophen-3-yl)sulfonyl-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13)-tetraene Chemical compound S1C(C)=CC(S(=O)(=O)N2C=3C=CC=C4CNCCC(C=34)=C2)=C1C VFULUTRECSYTSU-UHFFFAOYSA-N 0.000 claims 1
- OLTLETMORSQJIZ-UHFFFAOYSA-N 3-(2-ethoxy-5-propan-2-ylphenyl)sulfonyl-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13)-tetraene Chemical compound CCOC1=CC=C(C(C)C)C=C1S(=O)(=O)N1C(C=CC=C2CNCC3)=C2C3=C1 OLTLETMORSQJIZ-UHFFFAOYSA-N 0.000 claims 1
- JPGKHXYTUDUDDO-UHFFFAOYSA-N 3-(2-methoxy-4-methylphenyl)sulfonyl-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13)-tetraene Chemical compound COC1=CC(C)=CC=C1S(=O)(=O)N1C(C=CC=C2CNCC3)=C2C3=C1 JPGKHXYTUDUDDO-UHFFFAOYSA-N 0.000 claims 1
- HDELXLQNDQWJBH-UHFFFAOYSA-N 3-(2-methoxy-5-methylphenyl)sulfonyl-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13)-tetraene Chemical compound COC1=CC=C(C)C=C1S(=O)(=O)N1C(C=CC=C2CNCC3)=C2C3=C1 HDELXLQNDQWJBH-UHFFFAOYSA-N 0.000 claims 1
- IQYOCENNLCSLCS-UHFFFAOYSA-N 3-(2-methoxy-6-methylphenyl)sulfonyl-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13)-tetraene Chemical compound COC1=CC=CC(C)=C1S(=O)(=O)N1C(C=CC=C2CNCC3)=C2C3=C1 IQYOCENNLCSLCS-UHFFFAOYSA-N 0.000 claims 1
- FBFUIFVARQJZSX-UHFFFAOYSA-N 3-(5-ethyl-2-methoxyphenyl)sulfonyl-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13)-tetraene Chemical compound CCC1=CC=C(OC)C(S(=O)(=O)N2C=3C=CC=C4CNCCC(C=34)=C2)=C1 FBFUIFVARQJZSX-UHFFFAOYSA-N 0.000 claims 1
- KPBYGOWJTXKKAM-UHFFFAOYSA-N 3-[4-fluoro-3-(trifluoromethyl)phenyl]sulfonyl-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13)-tetraene Chemical compound C1=C(C(F)(F)F)C(F)=CC=C1S(=O)(=O)N1C(C=CC=C2CNCC3)=C2C3=C1 KPBYGOWJTXKKAM-UHFFFAOYSA-N 0.000 claims 1
- 125000004861 4-isopropyl phenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims 1
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Classifications
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- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
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- C—CHEMISTRY; METALLURGY
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- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/06—Peri-condensed systems
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
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- Pharmacology & Pharmacy (AREA)
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- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Child & Adolescent Psychology (AREA)
- Hospice & Palliative Care (AREA)
- Anesthesiology (AREA)
- Nutrition Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE0700611 | 2007-03-13 | ||
| SE0700611-7 | 2007-03-13 | ||
| US202907P | 2007-11-05 | 2007-11-05 | |
| US61/002,029 | 2007-11-05 | ||
| PCT/EP2008/053002 WO2008110598A1 (en) | 2007-03-13 | 2008-03-13 | Tricyclic isoquinoline derivatives for treatment of obesity |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2008225753A1 true AU2008225753A1 (en) | 2008-09-18 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2008225753A Abandoned AU2008225753A1 (en) | 2007-03-13 | 2008-03-13 | Tricyclic isoquinoline derivatives for treatment of obesity |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US8138333B2 (enExample) |
| EP (1) | EP2134714A1 (enExample) |
| JP (1) | JP2010520917A (enExample) |
| CN (1) | CN101631787A (enExample) |
| AU (1) | AU2008225753A1 (enExample) |
| BR (1) | BRPI0808791A2 (enExample) |
| CA (1) | CA2679346A1 (enExample) |
| EA (1) | EA016592B1 (enExample) |
| NZ (1) | NZ579360A (enExample) |
| WO (1) | WO2008110598A1 (enExample) |
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| CA2724449C (en) | 2008-05-29 | 2017-05-30 | Albany Molecular Research, Inc. | 5-ht3 receptor modulators, methods of making, and use thereof |
| EP2575815A4 (en) | 2010-06-04 | 2013-12-25 | Albany Molecular Res Inc | GLYCIN TRANSPORTER 1 INHIBITORS, METHODS OF MAKING THE SAME, AND USES THEREOF |
| WO2012106448A1 (en) * | 2011-02-02 | 2012-08-09 | Biocryst Pharmaceuticals, Inc. | Heterocyclic compounds as janus kinase inhibitors |
| JP6198715B2 (ja) * | 2012-03-06 | 2017-09-20 | 武田薬品工業株式会社 | 三環性化合物 |
| US10675283B2 (en) | 2017-03-24 | 2020-06-09 | University Of South Florida | Compositions and methods for white to beige adipogenesis |
| CN109180687A (zh) * | 2018-08-31 | 2019-01-11 | 山东轩德医药科技有限公司 | 一种瑞卡帕步中间体的制备方法 |
| CN111961047A (zh) * | 2020-08-19 | 2020-11-20 | 南通大学 | 一种6-乙氧基-3,4-二氢-2,7-萘啶-1（2h）-酮及其合成方法 |
| CN115925658B (zh) * | 2022-11-21 | 2024-02-27 | 常州佳德医药科技有限公司 | 一种2-氨基乙基呋喃的制备方法 |
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| BE795451A (fr) * | 1972-02-23 | 1973-08-16 | Pfizer | Agents hypoglycemiants aza indoliques tricycliques |
| US3950343A (en) * | 1973-11-06 | 1976-04-13 | Ayerst, Mckenna And Harrison Ltd. | Pyrroloisoquinoline derivatives |
| MX9700693A (es) | 1994-07-26 | 1997-04-30 | Pfizer | Derivados del 4-indol. |
| US6133287A (en) * | 1998-03-24 | 2000-10-17 | Allelix Biopharmaceuticals Inc. | Piperidine-indole compounds having 5-HT6 affinity |
| GB9820113D0 (en) | 1998-09-15 | 1998-11-11 | Merck Sharp & Dohme | Therapeutic agents |
| MXPA01005905A (es) | 1998-12-11 | 2002-09-18 | Univ Virginia Commonwealth | Ligandos selectivos de receptores de 5-ht6. |
| WO2002032863A1 (en) | 2000-10-20 | 2002-04-25 | Biovitrum Ab | 2-, 3-, 4-, or 5-substituted-n1-(benzensulfonyl)indoles and their use in therapy |
| PL374401A1 (en) * | 2002-06-05 | 2005-10-17 | F.Hoffmann-La Roche Ag | 1-sulfonyl-4-aminoalkoxy indole derivatives as 5-ht6-receptor modulators for the treatment of cns-disorders |
-
2008
- 2008-03-13 BR BRPI0808791A patent/BRPI0808791A2/pt not_active IP Right Cessation
- 2008-03-13 EP EP08717746A patent/EP2134714A1/en not_active Withdrawn
- 2008-03-13 US US12/075,979 patent/US8138333B2/en not_active Expired - Fee Related
- 2008-03-13 JP JP2009553146A patent/JP2010520917A/ja not_active Withdrawn
- 2008-03-13 AU AU2008225753A patent/AU2008225753A1/en not_active Abandoned
- 2008-03-13 WO PCT/EP2008/053002 patent/WO2008110598A1/en not_active Ceased
- 2008-03-13 CN CN200880008061A patent/CN101631787A/zh active Pending
- 2008-03-13 EA EA200970849A patent/EA016592B1/ru not_active IP Right Cessation
- 2008-03-13 CA CA002679346A patent/CA2679346A1/en not_active Abandoned
- 2008-03-13 NZ NZ579360A patent/NZ579360A/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| CA2679346A1 (en) | 2008-09-18 |
| CN101631787A (zh) | 2010-01-20 |
| US20080293694A1 (en) | 2008-11-27 |
| BRPI0808791A2 (pt) | 2017-05-02 |
| WO2008110598A1 (en) | 2008-09-18 |
| EP2134714A1 (en) | 2009-12-23 |
| EA200970849A1 (ru) | 2010-04-30 |
| JP2010520917A (ja) | 2010-06-17 |
| NZ579360A (en) | 2011-06-30 |
| EA016592B1 (ru) | 2012-06-29 |
| US8138333B2 (en) | 2012-03-20 |
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