CA2379544A1 - New stilbenes with vascular damaging activity - Google Patents
New stilbenes with vascular damaging activity Download PDFInfo
- Publication number
- CA2379544A1 CA2379544A1 CA002379544A CA2379544A CA2379544A1 CA 2379544 A1 CA2379544 A1 CA 2379544A1 CA 002379544 A CA002379544 A CA 002379544A CA 2379544 A CA2379544 A CA 2379544A CA 2379544 A1 CA2379544 A1 CA 2379544A1
- Authority
- CA
- Canada
- Prior art keywords
- compounds
- cis
- stilbene
- formula
- alkyl
- 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
- 230000000254 damaging effect Effects 0.000 title abstract description 11
- 230000002792 vascular Effects 0.000 title description 11
- 235000021286 stilbenes Nutrition 0.000 title description 4
- 150000001629 stilbenes Chemical class 0.000 title description 3
- 238000011282 treatment Methods 0.000 claims abstract description 21
- 229940002612 prodrug Drugs 0.000 claims abstract description 20
- 239000000651 prodrug Substances 0.000 claims abstract description 20
- -1 phosphate ester Chemical class 0.000 claims abstract description 16
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 13
- 150000003839 salts Chemical class 0.000 claims abstract description 9
- 206010029113 Neovascularisation Diseases 0.000 claims abstract description 7
- 125000004414 alkyl thio group Chemical group 0.000 claims abstract description 6
- 239000001257 hydrogen Substances 0.000 claims abstract description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 6
- 229910019142 PO4 Inorganic materials 0.000 claims abstract description 4
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 4
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 4
- 125000000304 alkynyl group Chemical group 0.000 claims abstract description 4
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims abstract description 3
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims abstract description 3
- 125000001188 haloalkyl group Chemical group 0.000 claims abstract description 3
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims abstract description 3
- 125000001475 halogen functional group Chemical group 0.000 claims abstract 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract 3
- 239000010452 phosphate Substances 0.000 claims abstract 3
- PJANXHGTPQOBST-QXMHVHEDSA-N cis-stilbene Chemical compound C=1C=CC=CC=1/C=C\C1=CC=CC=C1 PJANXHGTPQOBST-QXMHVHEDSA-N 0.000 claims description 22
- 239000000203 mixture Substances 0.000 claims description 16
- 238000002360 preparation method Methods 0.000 claims description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 239000012453 solvate Substances 0.000 claims description 2
- ALIRNEGJDQQVHO-FPLPWBNLSA-N 2-methyl-5-[(z)-2-(3,4,5-trimethoxyphenyl)ethenyl]phenol Chemical compound COC1=C(OC)C(OC)=CC(\C=C/C=2C=C(O)C(C)=CC=2)=C1 ALIRNEGJDQQVHO-FPLPWBNLSA-N 0.000 claims 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims 1
- UAXYYNUZYVSJKT-FPLPWBNLSA-N [2-methyl-5-[(z)-2-(3,4,5-trimethoxyphenyl)ethenyl]phenyl] dihydrogen phosphate Chemical compound COC1=C(OC)C(OC)=CC(\C=C/C=2C=C(OP(O)(O)=O)C(C)=CC=2)=C1 UAXYYNUZYVSJKT-FPLPWBNLSA-N 0.000 claims 1
- 150000001733 carboxylic acid esters Chemical class 0.000 claims 1
- 229910021653 sulphate ion Inorganic materials 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 52
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- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 7
- 230000001225 therapeutic effect Effects 0.000 abstract description 2
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- 206010028980 Neoplasm Diseases 0.000 description 29
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
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- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- 239000000243 solution Substances 0.000 description 14
- 239000002904 solvent Substances 0.000 description 14
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 11
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- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 8
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- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
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- 229910052943 magnesium sulfate Inorganic materials 0.000 description 4
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- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 4
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- 206010012689 Diabetic retinopathy Diseases 0.000 description 3
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 201000004681 Psoriasis Diseases 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
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- 238000004587 chromatography analysis Methods 0.000 description 3
- NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 3
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- 238000003756 stirring Methods 0.000 description 3
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- 125000004665 trialkylsilyl group Chemical group 0.000 description 3
- KJUGUADJHNHALS-UHFFFAOYSA-N 1H-tetrazole Chemical compound C=1N=NNN=1 KJUGUADJHNHALS-UHFFFAOYSA-N 0.000 description 2
- NUXPCIRLSHZTNH-UHFFFAOYSA-N 3-[tert-butyl(dimethyl)silyl]oxy-4-methylbenzaldehyde Chemical compound CC1=CC=C(C=O)C=C1O[Si](C)(C)C(C)(C)C NUXPCIRLSHZTNH-UHFFFAOYSA-N 0.000 description 2
- LGZKGOGODCLQHG-CYBMUJFWSA-N 5-[(2r)-2-hydroxy-2-(3,4,5-trimethoxyphenyl)ethyl]-2-methoxyphenol Chemical compound C1=C(O)C(OC)=CC=C1C[C@@H](O)C1=CC(OC)=C(OC)C(OC)=C1 LGZKGOGODCLQHG-CYBMUJFWSA-N 0.000 description 2
- 208000037260 Atherosclerotic Plaque Diseases 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
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- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
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- UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 description 1
- 229960000303 topotecan Drugs 0.000 description 1
- XFCLJVABOIYOMF-QPLCGJKRSA-N toremifene Chemical compound C1=CC(OCCN(C)C)=CC=C1C(\C=1C=CC=CC=1)=C(\CCCl)C1=CC=CC=C1 XFCLJVABOIYOMF-QPLCGJKRSA-N 0.000 description 1
- 229960005026 toremifene Drugs 0.000 description 1
- PJANXHGTPQOBST-VAWYXSNFSA-N trans-stilbene Chemical compound C=1C=CC=CC=1/C=C/C1=CC=CC=C1 PJANXHGTPQOBST-VAWYXSNFSA-N 0.000 description 1
- 229960000575 trastuzumab Drugs 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 1
- 239000005483 tyrosine kinase inhibitor Substances 0.000 description 1
- 229960003048 vinblastine Drugs 0.000 description 1
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
- 229960004528 vincristine Drugs 0.000 description 1
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
- GBABOYUKABKIAF-GHYRFKGUSA-N vinorelbine Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC GBABOYUKABKIAF-GHYRFKGUSA-N 0.000 description 1
- 229960002066 vinorelbine Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C43/00—Ethers; Compounds having groups, groups or groups
- C07C43/02—Ethers
- C07C43/20—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring
- C07C43/23—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring containing hydroxy or O-metal groups
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/52—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an inorganic compound, e.g. an inorganic ion that is complexed with the active ingredient
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/06—Phosphorus compounds without P—C bonds
- C07F9/08—Esters of oxyacids of phosphorus
- C07F9/09—Esters of phosphoric acids
- C07F9/12—Esters of phosphoric acids with hydroxyaryl compounds
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Inorganic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9918912.8 | 1999-08-12 | ||
| GBGB9918912.8A GB9918912D0 (en) | 1999-08-12 | 1999-08-12 | New stilbenes with vascular damaging activity |
| PCT/GB2000/003067 WO2001012579A2 (en) | 1999-08-12 | 2000-08-09 | New stilbenes with vascular damaging activity |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2379544A1 true CA2379544A1 (en) | 2001-02-22 |
Family
ID=10858950
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002379544A Abandoned CA2379544A1 (en) | 1999-08-12 | 2000-08-09 | New stilbenes with vascular damaging activity |
Country Status (6)
| Country | Link |
|---|---|
| EP (1) | EP1206429A2 (it) |
| JP (1) | JP2003507356A (it) |
| CA (1) | CA2379544A1 (it) |
| GB (1) | GB9918912D0 (it) |
| NZ (1) | NZ517069A (it) |
| WO (1) | WO2001012579A2 (it) |
Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1068870B1 (en) | 1998-04-03 | 2006-06-07 | Ajinomoto Co., Inc. | Antitumor agents |
| GB0019944D0 (en) | 2000-08-15 | 2000-09-27 | Angiogene Pharm Ltd | Compositions with vascular damaging activity |
| AU2002216228A1 (en) | 2000-12-21 | 2002-07-01 | Cancer Research Ventures Limited | Substituted stilbenes, their reactions and anticancer activity |
| FR2838437B1 (fr) | 2002-04-11 | 2004-06-04 | Aventis Pharma Sa | Procedes de preparation de combretastatines |
| GB0306908D0 (en) * | 2003-03-26 | 2003-04-30 | Angiogene Pharm Ltd | Bioreductively activated stilbene prodrugs |
| TW200533636A (en) | 2003-12-16 | 2005-10-16 | Gtx Inc | Prodrugs of selective androgen receptor modulators and methods of use thereof |
| CN1723884A (zh) * | 2004-07-21 | 2006-01-25 | 中国人民解放军军事医学科学院放射医学研究所 | 顺式－1，2－取代的二苯乙烯衍生物用于制备治疗或预防糖尿病的药物的用途 |
| CN101085743B (zh) * | 2006-06-06 | 2012-02-15 | 浙江大德药业集团有限公司 | 含氟烷氧基康普立停衍生物及制法和用途 |
| JP5302328B2 (ja) | 2007-11-21 | 2013-10-02 | オキシジーン， インコーポレイテッド | 造血性新生物を治療するための方法 |
| JP2011016777A (ja) * | 2009-07-10 | 2011-01-27 | Nipro Corp | 新規システイン誘導体 |
| EP2609089A1 (en) | 2010-08-27 | 2013-07-03 | Universität des Saarlandes | Selective 17beta-hydroxysteroid dehydrogenase type 1 inhibitors |
| US9353150B2 (en) | 2012-12-04 | 2016-05-31 | Massachusetts Institute Of Technology | Substituted pyrazino[1′,2′:1 ,5]pyrrolo[2,3-b]-indole-1,4-diones for cancer treatment |
| US10201623B2 (en) | 2013-03-15 | 2019-02-12 | Memorial Sloan Kettering Cancer Center | HSP90-targeted cardiac imaging and therapy |
| EP3337495A4 (en) | 2015-08-18 | 2019-04-10 | Mateon Therapeutics, Inc. | USE OF VDA TO ENHANCE IMMUNOMODULATION THERAPIES AGAINST TUMORS |
| WO2017197045A1 (en) | 2016-05-11 | 2017-11-16 | Movassaghi Mohammad | Convergent and enantioselective total synthesis of communesin analogs |
| WO2018209239A1 (en) | 2017-05-11 | 2018-11-15 | Massachusetts Institute Of Technology | Potent agelastatin derivatives as modulators for cancer invasion and metastasis |
| US10640508B2 (en) | 2017-10-13 | 2020-05-05 | Massachusetts Institute Of Technology | Diazene directed modular synthesis of compounds with quaternary carbon centers |
| WO2020092134A1 (en) | 2018-10-29 | 2020-05-07 | Cepheid | Exponential base-3 nucleic acid amplification with reduced amplification time using nested overlapping primers |
| US11535634B2 (en) | 2019-06-05 | 2022-12-27 | Massachusetts Institute Of Technology | Compounds, conjugates, and compositions of epipolythiodiketopiperazines and polythiodiketopiperazines and uses thereof |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9106177D0 (en) * | 1991-03-22 | 1991-05-08 | Aston Molecules Ltd | Substituted diphenylethylenes and analogues or derivatives thereof |
| TW325458B (en) * | 1993-09-08 | 1998-01-21 | Ajinomoto Kk | Stilbene derivatives and pharmaceutical compositions comprising the same for anti-cancer |
| US5561122A (en) * | 1994-12-22 | 1996-10-01 | Arizona Board Of Regents Acting On Behalf Of Arizona State University | Combretastatin A-4 prodrug |
| GB9903403D0 (en) * | 1999-02-16 | 1999-04-07 | Angiogene Pharm Ltd | Substituted stilbene compounds with vascular damaging activity |
-
1999
- 1999-08-12 GB GBGB9918912.8A patent/GB9918912D0/en not_active Ceased
-
2000
- 2000-08-09 WO PCT/GB2000/003067 patent/WO2001012579A2/en not_active Application Discontinuation
- 2000-08-09 NZ NZ517069A patent/NZ517069A/en unknown
- 2000-08-09 JP JP2001516880A patent/JP2003507356A/ja active Pending
- 2000-08-09 EP EP00951727A patent/EP1206429A2/en not_active Withdrawn
- 2000-08-09 CA CA002379544A patent/CA2379544A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| EP1206429A2 (en) | 2002-05-22 |
| WO2001012579A2 (en) | 2001-02-22 |
| WO2001012579A3 (en) | 2001-10-11 |
| NZ517069A (en) | 2004-04-30 |
| GB9918912D0 (en) | 1999-10-13 |
| JP2003507356A (ja) | 2003-02-25 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Dead |