ZA200200341B - Substituted isoquinoline derivatives and their use as anticonvulsants. - Google Patents
Substituted isoquinoline derivatives and their use as anticonvulsants. Download PDFInfo
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- ZA200200341B ZA200200341B ZA200200341A ZA200200341A ZA200200341B ZA 200200341 B ZA200200341 B ZA 200200341B ZA 200200341 A ZA200200341 A ZA 200200341A ZA 200200341 A ZA200200341 A ZA 200200341A ZA 200200341 B ZA200200341 B ZA 200200341B
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- ZA
- South Africa
- Prior art keywords
- disorders
- chloro
- compound
- tetrahydroisoquinolin
- disease
- Prior art date
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- 239000001961 anticonvulsive agent Substances 0.000 title claims description 14
- 229940125681 anticonvulsant agent Drugs 0.000 title description 3
- 125000002183 isoquinolinyl group Chemical class C1(=NC=CC2=CC=CC=C12)* 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 104
- 229910052739 hydrogen Inorganic materials 0.000 claims description 34
- 238000002360 preparation method Methods 0.000 claims description 34
- 239000001257 hydrogen Substances 0.000 claims description 33
- 238000000034 method Methods 0.000 claims description 33
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 27
- 150000003839 salts Chemical class 0.000 claims description 21
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 19
- 208000035475 disorder Diseases 0.000 claims description 19
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 claims description 16
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 16
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 claims description 16
- 201000006417 multiple sclerosis Diseases 0.000 claims description 16
- 230000001537 neural effect Effects 0.000 claims description 16
- 208000004296 neuralgia Diseases 0.000 claims description 16
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 14
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 10
- 230000000694 effects Effects 0.000 claims description 10
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- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 claims description 8
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- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- 238000011321 prophylaxis Methods 0.000 claims description 7
- 230000009529 traumatic brain injury Effects 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 6
- QLVXLDYLQRPQFH-UHFFFAOYSA-N 3-acetyl-n-(5,8-dichloro-1,2,3,4-tetrahydroisoquinolin-7-yl)-4-propan-2-yloxybenzamide Chemical compound C1=C(C(C)=O)C(OC(C)C)=CC=C1C(=O)NC1=CC(Cl)=C(CCNC2)C2=C1Cl QLVXLDYLQRPQFH-UHFFFAOYSA-N 0.000 claims description 4
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- 150000001557 benzodiazepines Chemical class 0.000 claims 3
- YKYIFUROKBDHCY-ONEGZZNKSA-N (e)-4-ethoxy-1,1,1-trifluorobut-3-en-2-one Chemical group CCO\C=C\C(=O)C(F)(F)F YKYIFUROKBDHCY-ONEGZZNKSA-N 0.000 claims 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 52
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- 239000000203 mixture Substances 0.000 description 29
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
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- 125000000217 alkyl group Chemical group 0.000 description 8
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 8
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- 238000001704 evaporation Methods 0.000 description 7
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- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 239000012267 brine Substances 0.000 description 6
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 5
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 5
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- UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 4
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- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
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- 125000001424 substituent group Chemical group 0.000 description 4
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- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
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- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
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- GPVDHNVGGIAOQT-UHFFFAOYSA-N 2,4-dimethoxybenzoic acid Chemical compound COC1=CC=C(C(O)=O)C(OC)=C1 GPVDHNVGGIAOQT-UHFFFAOYSA-N 0.000 description 2
- CSFDQFSRAYXLLC-UHFFFAOYSA-N 3-acetyl-n-(5,8-dichloro-1,2,3,4-tetrahydroisoquinolin-7-yl)-4-ethoxybenzamide Chemical compound C1=C(C(C)=O)C(OCC)=CC=C1C(=O)NC1=CC(Cl)=C(CCNC2)C2=C1Cl CSFDQFSRAYXLLC-UHFFFAOYSA-N 0.000 description 2
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- SJSINRIOAOMGCK-UHFFFAOYSA-N 3-bromo-n-(5-chloro-1,2,3,4-tetrahydroisoquinolin-7-yl)-4-methoxybenzamide Chemical compound C1=C(Br)C(OC)=CC=C1C(=O)NC1=CC(Cl)=C(CCNC2)C2=C1 SJSINRIOAOMGCK-UHFFFAOYSA-N 0.000 description 2
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- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/02—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/02—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines
- C07D217/04—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Neurology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Psychiatry (AREA)
- Addiction (AREA)
- Pain & Pain Management (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Psychology (AREA)
- Vascular Medicine (AREA)
- Anesthesiology (AREA)
- Urology & Nephrology (AREA)
- Hospice & Palliative Care (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GBGB9915589.7A GB9915589D0 (en) | 1999-07-02 | 1999-07-02 | Novel compounds |
Publications (1)
Publication Number | Publication Date |
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ZA200200341B true ZA200200341B (en) | 2004-01-28 |
Family
ID=10856577
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
ZA200200341A ZA200200341B (en) | 1999-07-02 | 2002-01-15 | Substituted isoquinoline derivatives and their use as anticonvulsants. |
Country Status (30)
Country | Link |
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US (3) | US6492388B1 (da) |
EP (2) | EP1200409B1 (da) |
JP (2) | JP4108977B2 (da) |
KR (1) | KR20020016879A (da) |
CN (1) | CN1192022C (da) |
AR (1) | AR029375A1 (da) |
AT (2) | ATE307115T1 (da) |
AU (1) | AU762716B2 (da) |
BR (1) | BR0011862A (da) |
CA (2) | CA2376495A1 (da) |
CO (1) | CO5200763A1 (da) |
CY (1) | CY1105373T1 (da) |
CZ (1) | CZ20014721A3 (da) |
DE (2) | DE60008539T2 (da) |
DK (2) | DK1367055T3 (da) |
ES (2) | ES2214287T3 (da) |
GB (1) | GB9915589D0 (da) |
GC (1) | GC0000195A (da) |
HK (2) | HK1047090B (da) |
HU (1) | HUP0203210A3 (da) |
IL (1) | IL147103A0 (da) |
MX (1) | MXPA02000064A (da) |
MY (1) | MY123639A (da) |
NO (2) | NO20016273L (da) |
NZ (2) | NZ534600A (da) |
PL (1) | PL355845A1 (da) |
PT (1) | PT1200409E (da) |
SI (2) | SI1367055T1 (da) |
WO (1) | WO2001002366A2 (da) |
ZA (1) | ZA200200341B (da) |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20010016657A1 (en) * | 1997-03-18 | 2001-08-23 | Smithkline Beecham P.L.C. | Substituted isoquinoline derivatives and their use as anticonvulsants |
GB9915589D0 (en) * | 1999-07-02 | 1999-09-01 | Smithkline Beecham Plc | Novel compounds |
CN100341163C (zh) * | 2004-03-29 | 2007-10-03 | 宏齐科技股份有限公司 | 白光发光二极管单元 |
GB0518237D0 (en) * | 2005-09-07 | 2005-10-19 | Angeletti P Ist Richerche Bio | Therapeutic compounds |
EP2927215A1 (en) | 2014-04-03 | 2015-10-07 | Farma-Derma S.R.L. | Copper chelators |
Family Cites Families (58)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4022900A (en) | 1970-09-09 | 1977-05-10 | Marion Laboratories, Inc. | Compositions containing 1,2,3,4-tetrahydroisoquinolines used as hypotensive agents |
US4666556A (en) | 1986-05-12 | 1987-05-19 | International Business Machines Corporation | Trench sidewall isolation by polysilicon oxidation |
KR920020676A (ko) | 1991-04-09 | 1992-11-21 | 김광호 | 반도체 장치의 소자분리 방법 |
US5254873A (en) * | 1991-12-09 | 1993-10-19 | Motorola, Inc. | Trench structure having a germanium silicate region |
US5266813A (en) * | 1992-01-24 | 1993-11-30 | International Business Machines Corporation | Isolation technique for silicon germanium devices |
DE59409300D1 (de) * | 1993-06-23 | 2000-05-31 | Siemens Ag | Verfahren zur Herstellung von einem Isolationsgraben in einem Substrat für Smart-Power-Technologien |
US5406111A (en) * | 1994-03-04 | 1995-04-11 | Motorola Inc. | Protection device for an intergrated circuit and method of formation |
JP3271453B2 (ja) * | 1994-12-28 | 2002-04-02 | 三菱電機株式会社 | 半導体装置における素子分離領域の形成方法 |
US5455194A (en) * | 1995-03-06 | 1995-10-03 | Motorola Inc. | Encapsulation method for localized oxidation of silicon with trench isolation |
US5719085A (en) * | 1995-09-29 | 1998-02-17 | Intel Corporation | Shallow trench isolation technique |
TR199802745T2 (xx) | 1996-06-17 | 1999-04-21 | Smithkline Beecham Plc | �kameli benzamid t�revleri ve bunlar�n ihtiya�lar� durdurucu veya engelleyici maddeler olarak kullan�lmas�. |
US5793090A (en) * | 1997-01-10 | 1998-08-11 | Advanced Micro Devices, Inc. | Integrated circuit having multiple LDD and/or source/drain implant steps to enhance circuit performance |
DZ2446A1 (fr) * | 1997-03-18 | 2003-01-11 | Smithkline Beecham Plc | Nouveaux composés |
BR9809047A (pt) | 1997-03-18 | 2000-08-01 | Smithkline Beecham Plc | Derivados de isoquinolina substituìda e o uso dos mesmos como anticonvulsivantes |
GB9726695D0 (en) * | 1997-12-17 | 1998-02-18 | Smithkline Beecham Plc | Novel compounds |
US5837612A (en) * | 1997-08-01 | 1998-11-17 | Motorola, Inc. | Silicon chemical mechanical polish etch (CMP) stop for reduced trench fill erosion and method for formation |
US6136664A (en) * | 1997-08-07 | 2000-10-24 | International Business Machines Corporation | Filling of high aspect ratio trench isolation |
US6306722B1 (en) * | 1999-05-03 | 2001-10-23 | United Microelectronics Corp. | Method for fabricating shallow trench isolation structure |
US6013937A (en) * | 1997-09-26 | 2000-01-11 | Siemens Aktiengesellshaft | Buffer layer for improving control of layer thickness |
CA2307030A1 (en) * | 1997-10-24 | 1999-05-06 | Mervyn Thompson | Substituted isoquinoline derivatives and their use as anticonvulsants |
US5882983A (en) * | 1997-12-19 | 1999-03-16 | Advanced Micro Devices, Inc. | Trench isolation structure partially bound between a pair of low K dielectric structures |
KR100248888B1 (ko) * | 1998-01-07 | 2000-03-15 | 윤종용 | 트랜치 격리의 형성 방법 |
KR100275908B1 (ko) * | 1998-03-02 | 2000-12-15 | 윤종용 | 집적 회로에 트렌치 아이솔레이션을 형성하는방법 |
US6080618A (en) * | 1998-03-31 | 2000-06-27 | Siemens Aktiengesellschaft | Controllability of a buried device layer |
US6214696B1 (en) * | 1998-04-22 | 2001-04-10 | Texas Instruments - Acer Incorporated | Method of fabricating deep-shallow trench isolation |
US6168961B1 (en) * | 1998-05-21 | 2001-01-02 | Memc Electronic Materials, Inc. | Process for the preparation of epitaxial wafers for resistivity measurements |
US6146970A (en) * | 1998-05-26 | 2000-11-14 | Motorola Inc. | Capped shallow trench isolation and method of formation |
US6265282B1 (en) * | 1998-08-17 | 2001-07-24 | Micron Technology, Inc. | Process for making an isolation structure |
US6074931A (en) * | 1998-11-05 | 2000-06-13 | Vanguard International Semiconductor Corporation | Process for recess-free planarization of shallow trench isolation |
US6080637A (en) * | 1998-12-07 | 2000-06-27 | Taiwan Semiconductor Manufacturing Company | Shallow trench isolation technology to eliminate a kink effect |
US6548261B1 (en) * | 1998-12-30 | 2003-04-15 | Case Western Reserve University | Alzheimer model for drug screening |
US6037238A (en) * | 1999-01-04 | 2000-03-14 | Vanguard International Semiconductor Corporation | Process to reduce defect formation occurring during shallow trench isolation formation |
US6271143B1 (en) * | 1999-05-06 | 2001-08-07 | Motorola, Inc. | Method for preventing trench fill erosion |
TW413887B (en) * | 1999-06-09 | 2000-12-01 | Mosel Vitelic Inc | Method for forming trench-type power metal oxide semiconductor field effect transistor |
GB9915589D0 (en) * | 1999-07-02 | 1999-09-01 | Smithkline Beecham Plc | Novel compounds |
US6207531B1 (en) * | 1999-07-02 | 2001-03-27 | Promos Technologies, Inc. | Shallow trench isolation using UV/O3 passivation prior to trench fill |
US6524931B1 (en) * | 1999-07-20 | 2003-02-25 | Motorola, Inc. | Method for forming a trench isolation structure in an integrated circuit |
US6150212A (en) * | 1999-07-22 | 2000-11-21 | International Business Machines Corporation | Shallow trench isolation method utilizing combination of spacer and fill |
US6426278B1 (en) * | 1999-10-07 | 2002-07-30 | International Business Machines Corporation | Projection gas immersion laser dopant process (PGILD) fabrication of diffusion halos |
US6399512B1 (en) * | 2000-06-15 | 2002-06-04 | Cypress Semiconductor Corporation | Method of making metallization and contact structures in an integrated circuit comprising an etch stop layer |
US6365446B1 (en) * | 2000-07-03 | 2002-04-02 | Chartered Semiconductor Manufacturing Ltd. | Formation of silicided ultra-shallow junctions using implant through metal technology and laser annealing process |
US6468853B1 (en) * | 2000-08-18 | 2002-10-22 | Chartered Semiconductor Manufacturing Ltd. | Method of fabricating a shallow trench isolation structure with reduced local oxide recess near corner |
US6943078B1 (en) * | 2000-08-31 | 2005-09-13 | Micron Technology, Inc. | Method and structure for reducing leakage current in capacitors |
US6391731B1 (en) * | 2001-02-15 | 2002-05-21 | Chartered Semiconductor Manufacturing Ltd. | Activating source and drain junctions and extensions using a single laser anneal |
US6646322B2 (en) * | 2001-03-02 | 2003-11-11 | Amberwave Systems Corporation | Relaxed silicon germanium platform for high speed CMOS electronics and high speed analog circuits |
US6456370B1 (en) * | 2001-03-29 | 2002-09-24 | Fitel Usa Corp. | Method of measuring bending loss with an optical time domain reflectometer |
US6498383B2 (en) * | 2001-05-23 | 2002-12-24 | International Business Machines Corporation | Oxynitride shallow trench isolation and method of formation |
US20030049893A1 (en) * | 2001-06-08 | 2003-03-13 | Matthew Currie | Method for isolating semiconductor devices |
US6548399B1 (en) * | 2001-11-20 | 2003-04-15 | Intel Corporation | Method of forming a semiconductor device using a carbon doped oxide layer to control the chemical mechanical polishing of a dielectric layer |
US6656749B1 (en) * | 2001-12-13 | 2003-12-02 | Advanced Micro Devices, Inc. | In-situ monitoring during laser thermal annealing |
US6566228B1 (en) * | 2002-02-26 | 2003-05-20 | International Business Machines Corporation | Trench isolation processes using polysilicon-assisted fill |
US6613646B1 (en) * | 2002-03-25 | 2003-09-02 | Advanced Micro Devices, Inc. | Methods for reduced trench isolation step height |
US6548361B1 (en) * | 2002-05-15 | 2003-04-15 | Advanced Micro Devices, Inc. | SOI MOSFET and method of fabrication |
US6759702B2 (en) * | 2002-09-30 | 2004-07-06 | International Business Machines Corporation | Memory cell with vertical transistor and trench capacitor with reduced burried strap |
US6706586B1 (en) * | 2002-10-23 | 2004-03-16 | International Business Machines Corporation | Method of trench sidewall enhancement |
US6706581B1 (en) | 2002-10-29 | 2004-03-16 | Taiwan Semiconductor Manufacturing Company | Dual gate dielectric scheme: SiON for high performance devices and high k for low power devices |
US6888214B2 (en) * | 2002-11-12 | 2005-05-03 | Micron Technology, Inc. | Isolation techniques for reducing dark current in CMOS image sensors |
US6673696B1 (en) | 2003-01-14 | 2004-01-06 | Advanced Micro Devices, Inc. | Post trench fill oxidation process for strained silicon processes |
-
1999
- 1999-07-02 GB GBGB9915589.7A patent/GB9915589D0/en not_active Ceased
-
2000
- 2000-06-29 NZ NZ534600A patent/NZ534600A/xx unknown
- 2000-06-29 US US10/019,104 patent/US6492388B1/en not_active Expired - Fee Related
- 2000-06-29 DE DE60008539T patent/DE60008539T2/de not_active Expired - Lifetime
- 2000-06-29 BR BR0011862-1A patent/BR0011862A/pt not_active IP Right Cessation
- 2000-06-29 CN CNB008124183A patent/CN1192022C/zh not_active Expired - Fee Related
- 2000-06-29 AT AT03076336T patent/ATE307115T1/de not_active IP Right Cessation
- 2000-06-29 AU AU56928/00A patent/AU762716B2/en not_active Ceased
- 2000-06-29 CA CA002376495A patent/CA2376495A1/en not_active Abandoned
- 2000-06-29 WO PCT/GB2000/002500 patent/WO2001002366A2/en active IP Right Grant
- 2000-06-29 DE DE60023362T patent/DE60023362T2/de not_active Expired - Lifetime
- 2000-06-29 SI SI200030777T patent/SI1367055T1/sl unknown
- 2000-06-29 ES ES00942223T patent/ES2214287T3/es not_active Expired - Lifetime
- 2000-06-29 SI SI200030374T patent/SI1200409T1/xx unknown
- 2000-06-29 JP JP2001507806A patent/JP4108977B2/ja not_active Expired - Fee Related
- 2000-06-29 ES ES03076336T patent/ES2251665T3/es not_active Expired - Lifetime
- 2000-06-29 IL IL14710300A patent/IL147103A0/xx unknown
- 2000-06-29 NZ NZ516130A patent/NZ516130A/en unknown
- 2000-06-29 AT AT00942223T patent/ATE260259T1/de not_active IP Right Cessation
- 2000-06-29 MX MXPA02000064A patent/MXPA02000064A/es active IP Right Grant
- 2000-06-29 EP EP00942223A patent/EP1200409B1/en not_active Expired - Lifetime
- 2000-06-29 CZ CZ20014721A patent/CZ20014721A3/cs unknown
- 2000-06-29 DK DK03076336T patent/DK1367055T3/da active
- 2000-06-29 KR KR1020017016975A patent/KR20020016879A/ko not_active Application Discontinuation
- 2000-06-29 DK DK00942223T patent/DK1200409T3/da active
- 2000-06-29 HU HU0203210A patent/HUP0203210A3/hu unknown
- 2000-06-29 PT PT00942223T patent/PT1200409E/pt unknown
- 2000-06-29 EP EP03076336A patent/EP1367055B1/en not_active Expired - Lifetime
- 2000-06-29 CA CA002527931A patent/CA2527931A1/en not_active Abandoned
- 2000-06-29 PL PL00355845A patent/PL355845A1/xx not_active Application Discontinuation
- 2000-06-30 MY MYPI20003014 patent/MY123639A/en unknown
- 2000-06-30 AR ARP000103344A patent/AR029375A1/es unknown
- 2000-06-30 CO CO00049344A patent/CO5200763A1/es not_active Application Discontinuation
- 2000-07-02 GC GCP2000747 patent/GC0000195A/en active
-
2001
- 2001-12-20 NO NO20016273A patent/NO20016273L/no not_active Application Discontinuation
-
2002
- 2002-01-15 ZA ZA200200341A patent/ZA200200341B/en unknown
- 2002-09-11 US US10/241,621 patent/US6770657B2/en not_active Expired - Fee Related
- 2002-09-27 HK HK02107175.0A patent/HK1047090B/zh unknown
- 2002-09-27 HK HK04103853A patent/HK1062436A1/xx not_active IP Right Cessation
-
2004
- 2004-01-12 US US10/755,748 patent/US7105536B2/en not_active Expired - Fee Related
-
2006
- 2006-01-10 CY CY20061100021T patent/CY1105373T1/el unknown
- 2006-03-07 NO NO20061099A patent/NO20061099L/no not_active Application Discontinuation
-
2007
- 2007-02-28 JP JP2007049789A patent/JP2007145862A/ja not_active Withdrawn
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