BRPI0710181A2 - compostos orgánicos - Google Patents
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- BRPI0710181A2 BRPI0710181A2 BRPI0710181-3A BRPI0710181A BRPI0710181A2 BR PI0710181 A2 BRPI0710181 A2 BR PI0710181A2 BR PI0710181 A BRPI0710181 A BR PI0710181A BR PI0710181 A2 BRPI0710181 A2 BR PI0710181A2
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Classifications
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- 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
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- 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
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
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- A—HUMAN NECESSITIES
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- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A—HUMAN NECESSITIES
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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- A—HUMAN NECESSITIES
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- 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
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- 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
Landscapes
- Health & Medical Sciences (AREA)
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- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Hall/Mr Elements (AREA)
- Mram Or Spin Memory Techniques (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
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| US78317506P | 2006-03-16 | 2006-03-16 | |
| US60/783,175 | 2006-03-16 | ||
| PCT/US2007/006424 WO2007109045A1 (en) | 2006-03-16 | 2007-03-14 | Heterocyclic organic compounds for the treatment of in particular melanoma |
Publications (1)
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| BRPI0710181A2 true BRPI0710181A2 (pt) | 2011-08-09 |
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| BRPI0710181-3A BRPI0710181A2 (pt) | 2006-03-16 | 2007-03-14 | compostos orgánicos |
Country Status (11)
| Country | Link |
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| US (2) | US20090069360A1 (enExample) |
| EP (1) | EP2001864A1 (enExample) |
| JP (1) | JP2009530288A (enExample) |
| KR (1) | KR20090052301A (enExample) |
| CN (1) | CN101563336A (enExample) |
| AU (1) | AU2007227602A1 (enExample) |
| BR (1) | BRPI0710181A2 (enExample) |
| CA (1) | CA2644356A1 (enExample) |
| MX (1) | MX2008011661A (enExample) |
| RU (1) | RU2008140382A (enExample) |
| WO (1) | WO2007109045A1 (enExample) |
Families Citing this family (171)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US8193206B2 (en) | 2005-06-14 | 2012-06-05 | Taigen Biotechnology Co., Ltd. | Pyrimidine compounds |
| EP1890703B1 (en) * | 2005-06-14 | 2016-05-11 | Taigen Biotechnology | Pyrimidine compounds as chemokine receptors inhibitors |
| US7879683B2 (en) * | 2007-10-09 | 2011-02-01 | Applied Materials, Inc. | Methods and apparatus of creating airgap in dielectric layers for the reduction of RC delay |
| PL2268635T3 (pl) | 2008-04-21 | 2015-11-30 | Taigen Biotechnology Co Ltd | Związki heterocykliczne |
| AU2009322346B2 (en) | 2008-12-03 | 2015-07-02 | The Scripps Research Institute | Stem cell cultures |
| WO2010085246A1 (en) * | 2009-01-21 | 2010-07-29 | Praecis Pharmaceuticals Inc | 2,4-diamino-1,3,5-triazine and 4, 6-diamino-pyrimidine derivatives and their use as aggrecanase inhibitors |
| TW201113269A (en) | 2009-06-24 | 2011-04-16 | Boehringer Ingelheim Int | New compounds, pharmaceutical composition and methods relating thereto |
| BR112012000831A2 (pt) | 2009-06-24 | 2019-09-24 | Boehringer Ingelheim Int | compostos, composições farmacêuticas e métodos relacionados |
| EP2918588B1 (en) | 2010-05-20 | 2017-05-03 | Array Biopharma, Inc. | Macrocyclic compounds as TRK kinase inhibitors |
| US9324576B2 (en) | 2010-05-27 | 2016-04-26 | Applied Materials, Inc. | Selective etch for silicon films |
| KR20120058113A (ko) * | 2010-11-29 | 2012-06-07 | 삼성전자주식회사 | 자기 터널 접합 구조체의 제조 방법 및 이를 이용하는 자기 메모리 소자의 제조 방법 |
| US10283321B2 (en) | 2011-01-18 | 2019-05-07 | Applied Materials, Inc. | Semiconductor processing system and methods using capacitively coupled plasma |
| EP2681193B1 (en) | 2011-03-02 | 2016-01-06 | Lead Discovery Center GmbH | Pharmaceutically active disubstituted pyridine derivatives |
| US9226929B2 (en) | 2011-03-02 | 2016-01-05 | Bayer Intellectual Property Gmbh | Pharmaceutically active disubstituted triazine derivatives |
| US9064815B2 (en) | 2011-03-14 | 2015-06-23 | Applied Materials, Inc. | Methods for etch of metal and metal-oxide films |
| US8999856B2 (en) | 2011-03-14 | 2015-04-07 | Applied Materials, Inc. | Methods for etch of sin films |
| US9082695B2 (en) | 2011-06-06 | 2015-07-14 | Avalanche Technology, Inc. | Vialess memory structure and method of manufacturing same |
| US8419953B1 (en) * | 2011-06-28 | 2013-04-16 | Western Digital (Fremont), Llc | Method and system for removing an antiferromagnetic seed structure |
| US8796795B2 (en) | 2011-08-01 | 2014-08-05 | Avalanche Technology Inc. | MRAM with sidewall protection and method of fabrication |
| US8709956B2 (en) | 2011-08-01 | 2014-04-29 | Avalanche Technology Inc. | MRAM with sidewall protection and method of fabrication |
| US8536063B2 (en) | 2011-08-30 | 2013-09-17 | Avalanche Technology Inc. | MRAM etching processes |
| KR20130034260A (ko) * | 2011-09-28 | 2013-04-05 | 에스케이하이닉스 주식회사 | 반도체 장치의 제조방법 |
| US8808563B2 (en) | 2011-10-07 | 2014-08-19 | Applied Materials, Inc. | Selective etch of silicon by way of metastable hydrogen termination |
| KR101881932B1 (ko) * | 2011-12-07 | 2018-07-27 | 삼성전자주식회사 | 자기 소자 및 그 제조 방법 |
| BR112014015720B1 (pt) * | 2011-12-30 | 2020-03-17 | Hanmi Pharm. Co., Ltd. | Derivados de tieno[3,2-d]pirimidina, composição farmacêutica e uso dos mesmos para a prevenção ou tratamento de uma doença causada por ativação anormal de uma proteína quinase |
| US8574928B2 (en) | 2012-04-10 | 2013-11-05 | Avalanche Technology Inc. | MRAM fabrication method with sidewall cleaning |
| CN102786512A (zh) | 2012-05-31 | 2012-11-21 | 中国人民解放军军事医学科学院毒物药物研究所 | N-芳基不饱和稠环叔胺类化合物及其制备方法和抗肿瘤应用 |
| US8883520B2 (en) | 2012-06-22 | 2014-11-11 | Avalanche Technology, Inc. | Redeposition control in MRAM fabrication process |
| US9267739B2 (en) | 2012-07-18 | 2016-02-23 | Applied Materials, Inc. | Pedestal with multi-zone temperature control and multiple purge capabilities |
| US9373517B2 (en) | 2012-08-02 | 2016-06-21 | Applied Materials, Inc. | Semiconductor processing with DC assisted RF power for improved control |
| US9023734B2 (en) | 2012-09-18 | 2015-05-05 | Applied Materials, Inc. | Radical-component oxide etch |
| US9390937B2 (en) | 2012-09-20 | 2016-07-12 | Applied Materials, Inc. | Silicon-carbon-nitride selective etch |
| US9132436B2 (en) | 2012-09-21 | 2015-09-15 | Applied Materials, Inc. | Chemical control features in wafer process equipment |
| US8969212B2 (en) | 2012-11-20 | 2015-03-03 | Applied Materials, Inc. | Dry-etch selectivity |
| US8980763B2 (en) | 2012-11-30 | 2015-03-17 | Applied Materials, Inc. | Dry-etch for selective tungsten removal |
| US9166154B2 (en) | 2012-12-07 | 2015-10-20 | Avalance Technology, Inc. | MTJ stack and bottom electrode patterning process with ion beam etching using a single mask |
| US8921234B2 (en) | 2012-12-21 | 2014-12-30 | Applied Materials, Inc. | Selective titanium nitride etching |
| US10256079B2 (en) | 2013-02-08 | 2019-04-09 | Applied Materials, Inc. | Semiconductor processing systems having multiple plasma configurations |
| US9362130B2 (en) | 2013-03-01 | 2016-06-07 | Applied Materials, Inc. | Enhanced etching processes using remote plasma sources |
| US9040422B2 (en) | 2013-03-05 | 2015-05-26 | Applied Materials, Inc. | Selective titanium nitride removal |
| CN103113349B (zh) * | 2013-03-15 | 2014-11-12 | 中国药科大学 | 4-咪唑基喹啉类及喹唑啉酮类芳香化酶抑制剂、制备方法和医药用途 |
| US20140271097A1 (en) | 2013-03-15 | 2014-09-18 | Applied Materials, Inc. | Processing systems and methods for halide scavenging |
| WO2014172639A1 (en) * | 2013-04-19 | 2014-10-23 | Ruga Corporation | Raf kinase inhibitors |
| US9493879B2 (en) * | 2013-07-12 | 2016-11-15 | Applied Materials, Inc. | Selective sputtering for pattern transfer |
| US9773648B2 (en) | 2013-08-30 | 2017-09-26 | Applied Materials, Inc. | Dual discharge modes operation for remote plasma |
| US9556170B2 (en) | 2013-08-30 | 2017-01-31 | University Of Utah Research Foundation | Substituted-1H-benzo[d]imidazole series compounds as lysine-specific demethylase 1 (LSD1) inhibitors |
| US9576809B2 (en) | 2013-11-04 | 2017-02-21 | Applied Materials, Inc. | Etch suppression with germanium |
| KR102101954B1 (ko) | 2013-11-05 | 2020-05-29 | 삼성전자주식회사 | 자기터널접합을 포함하는 자기 기억 소자 |
| US9520303B2 (en) | 2013-11-12 | 2016-12-13 | Applied Materials, Inc. | Aluminum selective etch |
| US9245762B2 (en) | 2013-12-02 | 2016-01-26 | Applied Materials, Inc. | Procedure for etch rate consistency |
| CN103738914B (zh) * | 2014-01-09 | 2016-01-20 | 上海华虹宏力半导体制造有限公司 | Mems器件的制造方法 |
| US9396989B2 (en) | 2014-01-27 | 2016-07-19 | Applied Materials, Inc. | Air gaps between copper lines |
| US9385028B2 (en) | 2014-02-03 | 2016-07-05 | Applied Materials, Inc. | Air gap process |
| US9499898B2 (en) | 2014-03-03 | 2016-11-22 | Applied Materials, Inc. | Layered thin film heater and method of fabrication |
| US9299537B2 (en) | 2014-03-20 | 2016-03-29 | Applied Materials, Inc. | Radial waveguide systems and methods for post-match control of microwaves |
| US9903020B2 (en) | 2014-03-31 | 2018-02-27 | Applied Materials, Inc. | Generation of compact alumina passivation layers on aluminum plasma equipment components |
| KR102105702B1 (ko) | 2014-04-04 | 2020-04-29 | 삼성전자주식회사 | 자기 기억 소자 |
| US9309598B2 (en) | 2014-05-28 | 2016-04-12 | Applied Materials, Inc. | Oxide and metal removal |
| US9378969B2 (en) | 2014-06-19 | 2016-06-28 | Applied Materials, Inc. | Low temperature gas-phase carbon removal |
| US9406523B2 (en) | 2014-06-19 | 2016-08-02 | Applied Materials, Inc. | Highly selective doped oxide removal method |
| US10003014B2 (en) | 2014-06-20 | 2018-06-19 | International Business Machines Corporation | Method of forming an on-pitch self-aligned hard mask for contact to a tunnel junction using ion beam etching |
| US9425058B2 (en) | 2014-07-24 | 2016-08-23 | Applied Materials, Inc. | Simplified litho-etch-litho-etch process |
| US9496167B2 (en) | 2014-07-31 | 2016-11-15 | Applied Materials, Inc. | Integrated bit-line airgap formation and gate stack post clean |
| US9378978B2 (en) | 2014-07-31 | 2016-06-28 | Applied Materials, Inc. | Integrated oxide recess and floating gate fin trimming |
| US9659753B2 (en) | 2014-08-07 | 2017-05-23 | Applied Materials, Inc. | Grooved insulator to reduce leakage current |
| US9553102B2 (en) | 2014-08-19 | 2017-01-24 | Applied Materials, Inc. | Tungsten separation |
| US9368364B2 (en) | 2014-09-24 | 2016-06-14 | Applied Materials, Inc. | Silicon etch process with tunable selectivity to SiO2 and other materials |
| US9478434B2 (en) | 2014-09-24 | 2016-10-25 | Applied Materials, Inc. | Chlorine-based hardmask removal |
| US9613822B2 (en) | 2014-09-25 | 2017-04-04 | Applied Materials, Inc. | Oxide etch selectivity enhancement |
| US9355922B2 (en) | 2014-10-14 | 2016-05-31 | Applied Materials, Inc. | Systems and methods for internal surface conditioning in plasma processing equipment |
| US9966240B2 (en) | 2014-10-14 | 2018-05-08 | Applied Materials, Inc. | Systems and methods for internal surface conditioning assessment in plasma processing equipment |
| US11637002B2 (en) | 2014-11-26 | 2023-04-25 | Applied Materials, Inc. | Methods and systems to enhance process uniformity |
| US10573496B2 (en) | 2014-12-09 | 2020-02-25 | Applied Materials, Inc. | Direct outlet toroidal plasma source |
| US10224210B2 (en) | 2014-12-09 | 2019-03-05 | Applied Materials, Inc. | Plasma processing system with direct outlet toroidal plasma source |
| US9502258B2 (en) | 2014-12-23 | 2016-11-22 | Applied Materials, Inc. | Anisotropic gap etch |
| US11257693B2 (en) | 2015-01-09 | 2022-02-22 | Applied Materials, Inc. | Methods and systems to improve pedestal temperature control |
| US9373522B1 (en) | 2015-01-22 | 2016-06-21 | Applied Mateials, Inc. | Titanium nitride removal |
| US9449846B2 (en) | 2015-01-28 | 2016-09-20 | Applied Materials, Inc. | Vertical gate separation |
| US9728437B2 (en) | 2015-02-03 | 2017-08-08 | Applied Materials, Inc. | High temperature chuck for plasma processing systems |
| US20160225652A1 (en) | 2015-02-03 | 2016-08-04 | Applied Materials, Inc. | Low temperature chuck for plasma processing systems |
| US9881805B2 (en) | 2015-03-02 | 2018-01-30 | Applied Materials, Inc. | Silicon selective removal |
| US20160260889A1 (en) | 2015-03-03 | 2016-09-08 | International Business Machines Corporation | Magnetic Tunnel Junction Patterning Using Low Atomic Weight Ion Sputtering |
| DK3322706T3 (da) | 2015-07-16 | 2021-02-01 | Array Biopharma Inc | Substituerede pyrazolo[1,5-a]pyridin-forbindelser som ret-kinaseinhibitorer |
| US9741593B2 (en) | 2015-08-06 | 2017-08-22 | Applied Materials, Inc. | Thermal management systems and methods for wafer processing systems |
| US9691645B2 (en) | 2015-08-06 | 2017-06-27 | Applied Materials, Inc. | Bolted wafer chuck thermal management systems and methods for wafer processing systems |
| US9349605B1 (en) | 2015-08-07 | 2016-05-24 | Applied Materials, Inc. | Oxide etch selectivity systems and methods |
| US10504700B2 (en) | 2015-08-27 | 2019-12-10 | Applied Materials, Inc. | Plasma etching systems and methods with secondary plasma injection |
| US9685604B2 (en) * | 2015-08-31 | 2017-06-20 | Taiwan Semiconductor Manufacturing Company, Ltd. | Magnetoresistive random access memory cell and fabricating the same |
| KR102323252B1 (ko) | 2015-10-07 | 2021-11-08 | 삼성전자주식회사 | 식각 부산물 검사 방법 및 이를 이용한 반도체 소자 제조 방법 |
| US9905751B2 (en) * | 2015-10-20 | 2018-02-27 | Taiwan Semiconductor Manufacturing Company, Ltd. | Magnetic tunnel junction with reduced damage |
| CN106676532B (zh) * | 2015-11-10 | 2019-04-05 | 江苏鲁汶仪器有限公司 | 金属刻蚀装置及方法 |
| US10522371B2 (en) | 2016-05-19 | 2019-12-31 | Applied Materials, Inc. | Systems and methods for improved semiconductor etching and component protection |
| US10504754B2 (en) | 2016-05-19 | 2019-12-10 | Applied Materials, Inc. | Systems and methods for improved semiconductor etching and component protection |
| US9865484B1 (en) | 2016-06-29 | 2018-01-09 | Applied Materials, Inc. | Selective etch using material modification and RF pulsing |
| US10872760B2 (en) * | 2016-07-26 | 2020-12-22 | Taiwan Semiconductor Manufacturing Co., Ltd. | Cluster tool and manufacuturing method of semiconductor structure using the same |
| US10629473B2 (en) | 2016-09-09 | 2020-04-21 | Applied Materials, Inc. | Footing removal for nitride spacer |
| US10062575B2 (en) | 2016-09-09 | 2018-08-28 | Applied Materials, Inc. | Poly directional etch by oxidation |
| US10062585B2 (en) | 2016-10-04 | 2018-08-28 | Applied Materials, Inc. | Oxygen compatible plasma source |
| US9721789B1 (en) | 2016-10-04 | 2017-08-01 | Applied Materials, Inc. | Saving ion-damaged spacers |
| US10546729B2 (en) | 2016-10-04 | 2020-01-28 | Applied Materials, Inc. | Dual-channel showerhead with improved profile |
| US9934942B1 (en) | 2016-10-04 | 2018-04-03 | Applied Materials, Inc. | Chamber with flow-through source |
| US10062579B2 (en) | 2016-10-07 | 2018-08-28 | Applied Materials, Inc. | Selective SiN lateral recess |
| JOP20190077A1 (ar) | 2016-10-10 | 2019-04-09 | Array Biopharma Inc | مركبات بيرازولو [1، 5-a]بيريدين بها استبدال كمثبطات كيناز ret |
| TWI704148B (zh) | 2016-10-10 | 2020-09-11 | 美商亞雷生物製藥股份有限公司 | 作為ret激酶抑制劑之經取代吡唑并[1,5-a]吡啶化合物 |
| US9947549B1 (en) | 2016-10-10 | 2018-04-17 | Applied Materials, Inc. | Cobalt-containing material removal |
| US9768034B1 (en) | 2016-11-11 | 2017-09-19 | Applied Materials, Inc. | Removal methods for high aspect ratio structures |
| US10163696B2 (en) | 2016-11-11 | 2018-12-25 | Applied Materials, Inc. | Selective cobalt removal for bottom up gapfill |
| US10242908B2 (en) | 2016-11-14 | 2019-03-26 | Applied Materials, Inc. | Airgap formation with damage-free copper |
| US10026621B2 (en) | 2016-11-14 | 2018-07-17 | Applied Materials, Inc. | SiN spacer profile patterning |
| US10566206B2 (en) | 2016-12-27 | 2020-02-18 | Applied Materials, Inc. | Systems and methods for anisotropic material breakthrough |
| WO2018136663A1 (en) | 2017-01-18 | 2018-07-26 | Array Biopharma, Inc. | Ret inhibitors |
| CA3049136C (en) | 2017-01-18 | 2022-06-14 | Array Biopharma Inc. | Substituted pyrazolo[1,5-a]pyrazine compounds as ret kinase inhibitors |
| US10431429B2 (en) | 2017-02-03 | 2019-10-01 | Applied Materials, Inc. | Systems and methods for radial and azimuthal control of plasma uniformity |
| US10403507B2 (en) | 2017-02-03 | 2019-09-03 | Applied Materials, Inc. | Shaped etch profile with oxidation |
| US10043684B1 (en) | 2017-02-06 | 2018-08-07 | Applied Materials, Inc. | Self-limiting atomic thermal etching systems and methods |
| US10319739B2 (en) | 2017-02-08 | 2019-06-11 | Applied Materials, Inc. | Accommodating imperfectly aligned memory holes |
| US10943834B2 (en) | 2017-03-13 | 2021-03-09 | Applied Materials, Inc. | Replacement contact process |
| JOP20190213A1 (ar) | 2017-03-16 | 2019-09-16 | Array Biopharma Inc | مركبات حلقية ضخمة كمثبطات لكيناز ros1 |
| US10319649B2 (en) | 2017-04-11 | 2019-06-11 | Applied Materials, Inc. | Optical emission spectroscopy (OES) for remote plasma monitoring |
| JP7176860B6 (ja) | 2017-05-17 | 2022-12-16 | アプライド マテリアルズ インコーポレイテッド | 前駆体の流れを改善する半導体処理チャンバ |
| US11276559B2 (en) | 2017-05-17 | 2022-03-15 | Applied Materials, Inc. | Semiconductor processing chamber for multiple precursor flow |
| US11276590B2 (en) | 2017-05-17 | 2022-03-15 | Applied Materials, Inc. | Multi-zone semiconductor substrate supports |
| US10497579B2 (en) | 2017-05-31 | 2019-12-03 | Applied Materials, Inc. | Water-free etching methods |
| US10049891B1 (en) | 2017-05-31 | 2018-08-14 | Applied Materials, Inc. | Selective in situ cobalt residue removal |
| US10920320B2 (en) | 2017-06-16 | 2021-02-16 | Applied Materials, Inc. | Plasma health determination in semiconductor substrate processing reactors |
| US10541246B2 (en) | 2017-06-26 | 2020-01-21 | Applied Materials, Inc. | 3D flash memory cells which discourage cross-cell electrical tunneling |
| US10727080B2 (en) | 2017-07-07 | 2020-07-28 | Applied Materials, Inc. | Tantalum-containing material removal |
| US10541184B2 (en) | 2017-07-11 | 2020-01-21 | Applied Materials, Inc. | Optical emission spectroscopic techniques for monitoring etching |
| US10354889B2 (en) | 2017-07-17 | 2019-07-16 | Applied Materials, Inc. | Non-halogen etching of silicon-containing materials |
| US10170336B1 (en) | 2017-08-04 | 2019-01-01 | Applied Materials, Inc. | Methods for anisotropic control of selective silicon removal |
| US10043674B1 (en) | 2017-08-04 | 2018-08-07 | Applied Materials, Inc. | Germanium etching systems and methods |
| US10297458B2 (en) | 2017-08-07 | 2019-05-21 | Applied Materials, Inc. | Process window widening using coated parts in plasma etch processes |
| TWI791053B (zh) | 2017-10-10 | 2023-02-01 | 美商亞雷生物製藥股份有限公司 | 6-(2-羥基-2-甲基丙氧基)-4-(6-(6-((6-甲氧基吡啶-3-基)甲基)-3,6-二氮雜雙環[3.1.1]庚-3-基)吡啶-3-基)吡唑并[1,5-a]吡啶-3-甲腈之結晶形式及其醫藥組合物 |
| TWI812649B (zh) | 2017-10-10 | 2023-08-21 | 美商絡速藥業公司 | 6-(2-羥基-2-甲基丙氧基)-4-(6-(6-((6-甲氧基吡啶-3-基)甲基)-3,6-二氮雜雙環[3.1.1]庚-3-基)吡啶-3-基)吡唑并[1,5-a]吡啶-3-甲腈之調配物 |
| US10128086B1 (en) | 2017-10-24 | 2018-11-13 | Applied Materials, Inc. | Silicon pretreatment for nitride removal |
| US10283324B1 (en) | 2017-10-24 | 2019-05-07 | Applied Materials, Inc. | Oxygen treatment for nitride etching |
| US10256112B1 (en) | 2017-12-08 | 2019-04-09 | Applied Materials, Inc. | Selective tungsten removal |
| US10903054B2 (en) | 2017-12-19 | 2021-01-26 | Applied Materials, Inc. | Multi-zone gas distribution systems and methods |
| US11328909B2 (en) | 2017-12-22 | 2022-05-10 | Applied Materials, Inc. | Chamber conditioning and removal processes |
| US10854426B2 (en) | 2018-01-08 | 2020-12-01 | Applied Materials, Inc. | Metal recess for semiconductor structures |
| WO2019143994A1 (en) | 2018-01-18 | 2019-07-25 | Array Biopharma Inc. | Substituted pyrazolyl[4,3-c]pyridinecompounds as ret kinase inhibitors |
| CA3087578C (en) | 2018-01-18 | 2023-08-08 | Array Biopharma Inc. | Substituted pyrazolo[3,4-d]pyrimidine compounds as ret kinase inhibitors |
| CA3087354C (en) | 2018-01-18 | 2023-01-03 | Array Biopharma Inc. | Substituted pyrrolo[2,3-d]pyrimidines compounds as ret kinase inhibitors |
| US10964512B2 (en) | 2018-02-15 | 2021-03-30 | Applied Materials, Inc. | Semiconductor processing chamber multistage mixing apparatus and methods |
| US10679870B2 (en) | 2018-02-15 | 2020-06-09 | Applied Materials, Inc. | Semiconductor processing chamber multistage mixing apparatus |
| TWI766433B (zh) | 2018-02-28 | 2022-06-01 | 美商應用材料股份有限公司 | 形成氣隙的系統及方法 |
| US10593560B2 (en) | 2018-03-01 | 2020-03-17 | Applied Materials, Inc. | Magnetic induction plasma source for semiconductor processes and equipment |
| US10319600B1 (en) | 2018-03-12 | 2019-06-11 | Applied Materials, Inc. | Thermal silicon etch |
| US10497573B2 (en) | 2018-03-13 | 2019-12-03 | Applied Materials, Inc. | Selective atomic layer etching of semiconductor materials |
| US10573527B2 (en) | 2018-04-06 | 2020-02-25 | Applied Materials, Inc. | Gas-phase selective etching systems and methods |
| US10490406B2 (en) | 2018-04-10 | 2019-11-26 | Appled Materials, Inc. | Systems and methods for material breakthrough |
| US10699879B2 (en) | 2018-04-17 | 2020-06-30 | Applied Materials, Inc. | Two piece electrode assembly with gap for plasma control |
| US10886137B2 (en) | 2018-04-30 | 2021-01-05 | Applied Materials, Inc. | Selective nitride removal |
| US10755941B2 (en) | 2018-07-06 | 2020-08-25 | Applied Materials, Inc. | Self-limiting selective etching systems and methods |
| US10872778B2 (en) | 2018-07-06 | 2020-12-22 | Applied Materials, Inc. | Systems and methods utilizing solid-phase etchants |
| US10672642B2 (en) | 2018-07-24 | 2020-06-02 | Applied Materials, Inc. | Systems and methods for pedestal configuration |
| CN112996794A (zh) | 2018-09-10 | 2021-06-18 | 阿雷生物药品公司 | 作为ret激酶抑制剂的稠合杂环化合物 |
| US10892198B2 (en) | 2018-09-14 | 2021-01-12 | Applied Materials, Inc. | Systems and methods for improved performance in semiconductor processing |
| US11049755B2 (en) | 2018-09-14 | 2021-06-29 | Applied Materials, Inc. | Semiconductor substrate supports with embedded RF shield |
| US11062887B2 (en) | 2018-09-17 | 2021-07-13 | Applied Materials, Inc. | High temperature RF heater pedestals |
| US11417534B2 (en) | 2018-09-21 | 2022-08-16 | Applied Materials, Inc. | Selective material removal |
| US11682560B2 (en) | 2018-10-11 | 2023-06-20 | Applied Materials, Inc. | Systems and methods for hafnium-containing film removal |
| US11121002B2 (en) | 2018-10-24 | 2021-09-14 | Applied Materials, Inc. | Systems and methods for etching metals and metal derivatives |
| US11437242B2 (en) | 2018-11-27 | 2022-09-06 | Applied Materials, Inc. | Selective removal of silicon-containing materials |
| US11721527B2 (en) | 2019-01-07 | 2023-08-08 | Applied Materials, Inc. | Processing chamber mixing systems |
| US10920319B2 (en) | 2019-01-11 | 2021-02-16 | Applied Materials, Inc. | Ceramic showerheads with conductive electrodes |
| US11121173B2 (en) | 2019-10-24 | 2021-09-14 | International Business Machines Corporation | Preserving underlying dielectric layer during MRAM device formation |
| US11271036B2 (en) | 2020-06-24 | 2022-03-08 | Sandisk Technologies Llc | Memory device containing dual etch stop layers for selector elements and method of making the same |
| US11849647B2 (en) | 2021-03-04 | 2023-12-19 | International Business Machines Corporation | Nonmetallic liner around a magnetic tunnel junction |
| US12207477B2 (en) | 2021-03-18 | 2025-01-21 | International Business Machines Corporation | Same level MRAM stacks having different configurations |
| WO2023107705A1 (en) | 2021-12-10 | 2023-06-15 | Incyte Corporation | Bicyclic amines as cdk12 inhibitors |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3233604A1 (de) * | 1982-09-10 | 1984-03-22 | Hoechst Ag, 6230 Frankfurt | Quartaere pyrimido(4,5-b)chinoliniumsalze und verfahren zu ihrer herstellung |
| US5854116A (en) * | 1987-01-20 | 1998-12-29 | Ohmi; Tadahiro | Semiconductor apparatus |
| HU206337B (en) * | 1988-12-29 | 1992-10-28 | Mitsui Petrochemical Ind | Process for producing pyrimidine derivatives and pharmaceutical compositions |
| DE4029648A1 (de) * | 1990-09-19 | 1992-03-26 | Hoechst Ag | 4-anilino-pyrimidine, verfahren zu ihrer herstellung, sie enthaltende mittel und ihre verwendung als fungizide |
| JP3103380B2 (ja) * | 1995-09-22 | 2000-10-30 | 湧永製薬株式会社 | 新規ピリドンカルボン酸誘導体又はその塩並びに該物質を有効成分とする抗菌剤 |
| GB9905075D0 (en) * | 1999-03-06 | 1999-04-28 | Zeneca Ltd | Chemical compounds |
| ES2306671T3 (es) * | 1999-10-07 | 2008-11-16 | Amgen Inc. | Inhibidores de triazina quinasa. |
| US7101869B2 (en) * | 1999-11-30 | 2006-09-05 | Pfizer Inc. | 2,4-diaminopyrimidine compounds useful as immunosuppressants |
| TR200201431T2 (tr) * | 1999-11-30 | 2002-09-23 | Pfizer Products Inc. | İmünosupresanlar olarak faydalı 2,4-diaminopirimidin bileşikleri |
| AU2001237041B9 (en) * | 2000-02-17 | 2005-07-28 | Amgen Inc. | Kinase inhibitors |
| JP4605554B2 (ja) * | 2000-07-25 | 2011-01-05 | 独立行政法人物質・材料研究機構 | ドライエッチング用マスク材 |
| US20020132823A1 (en) * | 2001-01-17 | 2002-09-19 | Jiahuai Han | Assay method |
| US6815248B2 (en) * | 2002-04-18 | 2004-11-09 | Infineon Technologies Ag | Material combinations for tunnel junction cap layer, tunnel junction hard mask and tunnel junction stack seed layer in MRAM processing |
| CA2538413A1 (en) * | 2003-09-18 | 2005-03-24 | Novartis Ag | 2,4-di (phenylamino) pyrimidines useful in the treatment of proliferative disorders |
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- 2007-03-14 EP EP07753076A patent/EP2001864A1/en not_active Withdrawn
- 2007-03-14 KR KR1020087022399A patent/KR20090052301A/ko not_active Withdrawn
- 2007-03-14 CA CA002644356A patent/CA2644356A1/en not_active Abandoned
- 2007-03-14 CN CNA2007800081401A patent/CN101563336A/zh active Pending
- 2007-03-14 MX MX2008011661A patent/MX2008011661A/es not_active Application Discontinuation
- 2007-03-14 WO PCT/US2007/006424 patent/WO2007109045A1/en not_active Ceased
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| AU2007227602A1 (en) | 2007-09-27 |
| US20090069360A1 (en) | 2009-03-12 |
| JP2009530288A (ja) | 2009-08-27 |
| CA2644356A1 (en) | 2007-09-27 |
| CN101563336A (zh) | 2009-10-21 |
| MX2008011661A (es) | 2008-09-22 |
| KR20090052301A (ko) | 2009-05-25 |
| US20100022030A1 (en) | 2010-01-28 |
| EP2001864A1 (en) | 2008-12-17 |
| WO2007109045A8 (en) | 2009-07-02 |
| US7955870B2 (en) | 2011-06-07 |
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