JP2013512899A5 - - Google Patents

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JP2013512899A5
JP2013512899A5 JP2012541997A JP2012541997A JP2013512899A5 JP 2013512899 A5 JP2013512899 A5 JP 2013512899A5 JP 2012541997 A JP2012541997 A JP 2012541997A JP 2012541997 A JP2012541997 A JP 2012541997A JP 2013512899 A5 JP2013512899 A5 JP 2013512899A5
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methyl
amino
piperazin
chlorophenyl
oxy
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JP2012541997A
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JP2013512899A (ja
JP5589090B2 (ja
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JP2012541997A 2009-12-04 2010-06-01 癌ならびに免疫疾患および自己免疫疾患の治療用のアポトーシス誘発剤 Active JP5589090B2 (ja)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US12/631,367 US20100160322A1 (en) 2008-12-04 2009-12-04 Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases
US12/631,367 2009-12-04
PCT/US2010/036844 WO2011068560A1 (en) 2009-12-04 2010-06-01 Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases

Publications (3)

Publication Number Publication Date
JP2013512899A JP2013512899A (ja) 2013-04-18
JP2013512899A5 true JP2013512899A5 (enExample) 2013-07-11
JP5589090B2 JP5589090B2 (ja) 2014-09-10

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JP2012541997A Active JP5589090B2 (ja) 2009-12-04 2010-06-01 癌ならびに免疫疾患および自己免疫疾患の治療用のアポトーシス誘発剤

Country Status (30)

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US (5) US20100160322A1 (enExample)
EP (1) EP2507211B1 (enExample)
JP (1) JP5589090B2 (enExample)
CN (2) CN106397418A (enExample)
AR (1) AR076946A1 (enExample)
AU (1) AU2010326727B2 (enExample)
BR (1) BR112012012918A8 (enExample)
CA (1) CA2781521A1 (enExample)
CL (1) CL2012001421A1 (enExample)
CO (1) CO6571908A2 (enExample)
CR (1) CR20120347A (enExample)
CY (1) CY1115502T1 (enExample)
DK (1) DK2507211T3 (enExample)
DO (1) DOP2012000154A (enExample)
EC (1) ECSP12012020A (enExample)
ES (1) ES2487617T3 (enExample)
IL (1) IL219991A (enExample)
MX (1) MX2012006391A (enExample)
MY (1) MY161340A (enExample)
NZ (1) NZ600084A (enExample)
PE (1) PE20121496A1 (enExample)
PH (1) PH12012501071A1 (enExample)
PL (1) PL2507211T3 (enExample)
PT (1) PT2507211E (enExample)
RU (1) RU2535203C2 (enExample)
SG (1) SG181506A1 (enExample)
SI (1) SI2507211T1 (enExample)
TW (1) TWI473801B (enExample)
UA (1) UA106403C2 (enExample)
WO (1) WO2011068560A1 (enExample)

Families Citing this family (51)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009061345A2 (en) 2007-11-07 2009-05-14 Cornell Research Foundation, Inc. Targeting cdk4 and cdk6 in cancer therapy
US20100160322A1 (en) 2008-12-04 2010-06-24 Abbott Laboratories Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases
US8557983B2 (en) * 2008-12-04 2013-10-15 Abbvie Inc. Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases
US8586754B2 (en) * 2008-12-05 2013-11-19 Abbvie Inc. BCL-2-selective apoptosis-inducing agents for the treatment of cancer and immune diseases
US8563735B2 (en) 2008-12-05 2013-10-22 Abbvie Inc. Bcl-2-selective apoptosis-inducing agents for the treatment of cancer and immune diseases
HUE025527T2 (en) * 2009-01-19 2016-04-28 Abbvie Inc Apoptosis inducers for the treatment of cancer, immune and autoimmune diseases
CN102282128B (zh) 2009-01-19 2015-06-17 Abbvie公司 用于治疗癌症和免疫和自身免疫疾病的细胞程序死亡诱导药剂
US9034875B2 (en) 2009-05-26 2015-05-19 Abbvie Inc. Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases
US8546399B2 (en) 2009-05-26 2013-10-01 Abbvie Inc. Apoptosis inducing agents for the treatment of cancer and immune and autoimmune diseases
CN102448959B (zh) * 2009-05-26 2015-06-17 艾伯维巴哈马有限公司 用于治疗癌症和免疫和自身免疫疾病的细胞程序死亡诱导药剂
US20220315555A1 (en) 2009-05-26 2022-10-06 Abbvie Inc. Apoptosis inducing agents for the treatment of cancer and immune and autoimmune diseases
RU2568611C2 (ru) 2010-03-25 2015-11-20 Эббви Инк. Средства, индуцирующие апоптоз, для лечения рака, иммунных и аутоиммунных заболеваний
TWI520960B (zh) * 2010-05-26 2016-02-11 艾伯維有限公司 用於治療癌症及免疫及自體免疫疾病之細胞凋亡誘導劑
CA3007787C (en) 2010-06-03 2020-03-10 Pharmacyclics Llc The use of inhibitors of bruton's tyrosine kinase (btk)
UA113500C2 (xx) * 2010-10-29 2017-02-10 Одержані екструзією розплаву тверді дисперсії, що містять індукуючий апоптоз засіб
CA2811805A1 (en) * 2010-10-29 2012-05-03 Abbvie Inc. Solid dispersions containing an apoptosis-inducing agent
SG190399A1 (en) 2010-11-23 2013-06-28 Abbvie Inc Methods of treatment using selective bcl-2 inhibitors
CN107266435A (zh) 2010-11-23 2017-10-20 Abbvie 公司 细胞凋亡诱导剂的盐和晶形
US8940737B2 (en) 2011-10-14 2015-01-27 Abbvie Inc. Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases
KR20250086805A (ko) * 2011-10-19 2025-06-13 파마싸이클릭스 엘엘씨 브루톤 티로신 인산화효소(btk)의 억제제의 용도
CA2879570A1 (en) 2012-07-24 2014-01-30 Pharmacyclics, Inc. Mutations associated with resistance to inhibitors of bruton's tyrosine kinase (btk)
EP3293185A1 (en) * 2013-03-13 2018-03-14 AbbVie Inc. Processes for the preparation of an apoptosis-inducing agent
US20140275082A1 (en) 2013-03-14 2014-09-18 Abbvie Inc. Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases
EP3099380B1 (en) 2014-01-28 2021-08-11 Buck Institute for Research on Aging Methods and compositions for killing senescent cells and for treating senescence-associated diseases and disorders
US20190269675A1 (en) 2014-01-28 2019-09-05 Buck Institute for Research and Aging Treatment of parkinson's disease and other conditions caused or mediated by senescent astrocytes using small molecule senolytic agents
US20170216286A1 (en) 2014-01-28 2017-08-03 Mayo Foundation For Medical Education And Research Killing senescent cells and treating senescence-associated conditions using a src inhibitor and a flavonoid
US10328058B2 (en) 2014-01-28 2019-06-25 Mayo Foundation For Medical Education And Research Treating atherosclerosis by removing senescent foam cell macrophages from atherosclerotic plaques
EP3119910A4 (en) 2014-03-20 2018-02-21 Pharmacyclics LLC Phospholipase c gamma 2 and resistance associated mutations
CA2946538A1 (en) 2014-04-04 2015-10-08 Del Mar Pharmaceuticals Use of dianhydrogalactitol and analogs or derivatives thereof to treat non-small-cell carcinoma of the lung and ovarian cancer
EP3179991B1 (en) 2014-08-11 2021-10-06 Acerta Pharma B.V. Therapeutic combinations of a btk inhibitor and a bcl-2 inhibitor
EP3798214B1 (en) 2014-10-06 2022-09-14 Vertex Pharmaceuticals Incorporated Modulators of cystic fibrosis transmembrane conductance regulator
US10195213B2 (en) 2015-03-13 2019-02-05 Unity Biotechnology, Inc. Chemical entities that kill senescent cells for use in treating age-related disease
EP3436446B1 (en) 2016-03-31 2023-06-07 Vertex Pharmaceuticals Incorporated Modulators of cystic fibrosis transmembrane conductance regulator
SG10201913595YA (en) 2016-09-30 2020-02-27 Vertex Pharma Modulator of cystic fibrosis transmembrane conductance regulator, pharmaceutical compositions, methods of treatment, and process for making the modulator
MA49235B1 (fr) * 2016-12-09 2021-02-26 Vertex Pharma Modulateur de régulateur de conductance transmembranaire de fibrose kystique, compositions pharmaceutiques, procédés de traitement et procédé de fabrication du modulateur
EP3634402B1 (en) 2017-06-08 2026-01-21 Vertex Pharmaceuticals Incorporated Methods of treatment for cystic fibrosis
WO2019001383A1 (zh) * 2017-06-26 2019-01-03 深圳市塔吉瑞生物医药有限公司 用于抑制Bcl-2蛋白的N-苯磺酰基苯甲酰胺类化合物及其组合物及应用
BR112020000941A2 (pt) 2017-07-17 2020-07-21 Vertex Pharmaceuticals Incorporated métodos de tratamento para fibrose cística
TWI799435B (zh) 2017-08-02 2023-04-21 美商維泰克斯製藥公司 製備化合物之製程
MX2020002033A (es) 2017-08-23 2020-08-20 Guangzhou Lupeng Pharmaceutical Company Ltd Derivados heterociclicos condensados como inhibidores de bcl-2 para el tratamiento de enfermedades neoplasticas.
IL273831B2 (en) 2017-10-19 2024-10-01 Vertex Pharma Crystalline forms and compositions of cftr modulators
CN111757874B (zh) 2017-12-08 2024-03-08 弗特克斯药品有限公司 用于制备囊性纤维化跨膜传导调节因子的调节剂的方法
CA3087262A1 (en) 2018-01-10 2019-07-18 Recurium Ip Holdings, Llc Benzamide compounds
TWI810243B (zh) 2018-02-05 2023-08-01 美商維泰克斯製藥公司 用於治療囊腫纖化症之醫藥組合物
US11414439B2 (en) 2018-04-13 2022-08-16 Vertex Pharmaceuticals Incorporated Modulators of cystic fibrosis transmembrane conductance regulator, pharmaceutical compositions, methods of treatment, and process for making the modulator
WO2020041405A1 (en) 2018-08-22 2020-02-27 Newave Pharmaceutical Inc. Bcl-2 inhibitors
CN109851535A (zh) * 2019-01-30 2019-06-07 天津现代职业技术学院 一种制备4-氟-3-(三氟甲磺酰基)苯磺酰胺的方法
US12552784B2 (en) 2019-12-27 2026-02-17 Newave Pharmaceutical Inc. 1H-pyrrolo[2,3-b]pyridine derivatives as BCL-2 inhibitors for the treatment of neoplastic and autoimmune diseases
CN113444078B (zh) * 2020-03-25 2023-07-07 中国科学院上海有机化学研究所 抗凋亡蛋白Bcl-2抑制剂及其制备方法和应用
CN111978246A (zh) * 2020-09-26 2020-11-24 安徽金禾实业股份有限公司 一种2-甲基-3-甲氧基-4-氯吡啶的纯化合成方法
WO2022218311A1 (en) * 2021-04-13 2022-10-20 Appicine Therapeutics (Hk) Limited Modulators of bcl-2 or bcl-2/bcl-xl and uses thereof

Family Cites Families (67)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE4126937A1 (de) 1991-08-10 1993-02-11 Basf Ag Salicyl(thio)etherderivate, verfahren und zwischenprodukte zu ihrer herstellung
JPH06510763A (ja) 1991-08-19 1994-12-01 イー・アイ・デュポン・ドゥ・ヌムール・アンド・カンパニー アンジオテンシン2受容体遮断イミダゾリノン誘導体
GB9203798D0 (en) 1992-02-21 1992-04-08 Fujisawa Pharmaceutical Co Quinolylbenzofuran derivatives,processes for preparation thereof and pharmaceutical composition comprising the same
MY115155A (en) 1993-09-09 2003-04-30 Upjohn Co Substituted oxazine and thiazine oxazolidinone antimicrobials.
EP1019385B1 (en) 1995-09-15 2004-01-14 PHARMACIA & UPJOHN COMPANY Aminoaryl oxazolidinone n-oxides
HUP0004529A3 (en) 1997-07-31 2001-05-28 American Home Prod Sulfonilated dipeptide-compounds which inhibit leukocyte adhesion mediated by vla-4, pharmaceutical compositions comprising thereof and their use
US20030220234A1 (en) * 1998-11-02 2003-11-27 Selvaraj Naicker Deuterated cyclosporine analogs and their use as immunodulating agents
US6410584B1 (en) 1998-01-14 2002-06-25 Cell Pathways, Inc. Method for inhibiting neoplastic cells with indole derivatives
JP4750272B2 (ja) 1998-02-04 2011-08-17 ノバルティス アーゲー マトリックス分解メタロプロテイナーゼを阻害するスルホニルアミノ誘導体
ATE416772T1 (de) 1998-07-06 2008-12-15 Bristol Myers Squibb Co Biphenylsulfonamide als zweifach aktive rezeptor antagonisten von angiotensin und endothelin
DE19830430A1 (de) * 1998-07-08 2000-01-13 Hoechst Marion Roussel De Gmbh Schwefelsubstituierte Sulfonylamino-carbonsäure-N-arylamide, ihre Herstellung, ihre Verwendung und sie enthaltende pharmazeutische Präparate
EP1149072B1 (en) 1998-12-22 2004-06-30 F. Hoffmann-La Roche Ag Sulfonamide hydroxamates
GB9918037D0 (en) * 1999-07-30 1999-09-29 Biochemie Gmbh Organic compounds
GEP20053476B (en) 1999-08-12 2005-03-25 Upjohn Co 3(5)-Amino-Pyrazole Derivatives, Process for Their Preparation and Their Use as Antitumor Agents
JP2003528082A (ja) 2000-03-21 2003-09-24 ザ プロクター アンド ギャンブル カンパニー ニフッ化酪酸メタロプロテアーゼ阻害物質
EP1265864A1 (en) 2000-03-21 2002-12-18 The Procter & Gamble Company Heterocyclic side chain containing, n-substituted metalloprotease inhibitors
US20020055631A1 (en) * 2000-09-20 2002-05-09 Augeri David J. N-acylsulfonamide apoptosis promoters
UY26942A1 (es) * 2000-09-20 2002-04-26 Abbott Lab N-acilsulfonamidas promotoras de la apoptosis
US6720338B2 (en) * 2000-09-20 2004-04-13 Abbott Laboratories N-acylsulfonamide apoptosis promoters
US6995162B2 (en) 2001-01-12 2006-02-07 Amgen Inc. Substituted alkylamine derivatives and methods of use
ATE335722T1 (de) * 2001-06-06 2006-09-15 Lilly Co Eli Benzoylsulfonamide und sulfonylbenzamidine zur verwendung als antitumor-mittel
UY27450A1 (es) 2001-09-24 2003-04-30 Bayer Corp Preparación y uso de derivados de imidazol para el tratamiento de la obesidad
AR043059A1 (es) 2002-11-12 2005-07-13 Bayer Pharmaceuticals Corp Derivados de indolil pirazinona utiles para el tratamiento de trastornos hiper-proliferativos
AU2003290592A1 (en) 2002-11-22 2004-06-18 Eli Lilly And Company Antitumor benzoylsulfonamides
WO2005024636A1 (ja) 2003-09-04 2005-03-17 Hitachi Ulsi Systems Co., Ltd. 半導体装置
US7767684B2 (en) * 2003-11-13 2010-08-03 Abbott Laboratories Apoptosis promoters
US7973161B2 (en) * 2003-11-13 2011-07-05 Abbott Laboratories Apoptosis promoters
US8614318B2 (en) * 2003-11-13 2013-12-24 Abbvie Inc. Apoptosis promoters
US7642260B2 (en) * 2003-11-13 2010-01-05 Abbott Laboratories, Inc. Apoptosis promoters
WO2005049593A2 (en) * 2003-11-13 2005-06-02 Abbott Laboratories N-acylsulfonamide apoptosis promoters
EP1697738A1 (en) * 2003-11-20 2006-09-06 Freshpoint Holdings Sa Method and system for determining the condition of a time-temperature indicator
RU2263666C1 (ru) 2004-04-08 2005-11-10 Общество с ограниченной ответственностью "Исследовательский Институт Химического Разнообразия" (ООО "Исследовательский Институт Химического Разнообразия") Гетероциклилсульфиновые кислоты и их производные, фокусированная библиотека и фармацевтическая композиция
EP1737850B1 (en) 2004-04-19 2007-10-03 Symed Labs Limited A novel process for the preparation of linezolid and related compounds
EP1768966B1 (en) 2004-06-17 2012-03-07 Infinity Discovery, Inc. Coumpounds and methods for inhibiting the interaction of bcl proteins with binding partners
US7429661B2 (en) 2004-07-20 2008-09-30 Symed Labs Limited Intermediates for linezolid and related compounds
JP2008514702A (ja) * 2004-09-29 2008-05-08 エーエムアール テクノロジー インコーポレイテッド 新規シクロスポリン類似体およびそれらの薬学的使用
US8624027B2 (en) 2005-05-12 2014-01-07 Abbvie Inc. Combination therapy for treating cancer and diagnostic assays for use therein
PT1888550E (pt) 2005-05-12 2014-09-03 Abbvie Bahamas Ltd Promotores de apoptose
TW200716636A (en) 2005-05-31 2007-05-01 Speedel Experimenta Ag Heterocyclic spiro-compounds
US7514068B2 (en) * 2005-09-14 2009-04-07 Concert Pharmaceuticals Inc. Biphenyl-pyrazolecarboxamide compounds
EP2061560A2 (en) 2006-09-05 2009-05-27 Abbott Laboratories Bcl inhibitors for treating platelet excess
US8796267B2 (en) 2006-10-23 2014-08-05 Concert Pharmaceuticals, Inc. Oxazolidinone derivatives and methods of use
US20100087436A1 (en) 2006-11-16 2010-04-08 Abbott Laboratories Method of preventing or treating organ, hematopoietic stem cell or bone marrow transplant rejection
US20080182845A1 (en) 2006-11-16 2008-07-31 Abbott Laboratories Method of preventing or treating organ, hematopoietic stem cell or bone marrow transplant rejection
KR101222412B1 (ko) 2007-02-15 2013-01-15 에프. 호프만-라 로슈 아게 Taar1 리간드로서의 2-아미노옥사졸린
KR20100012031A (ko) * 2007-04-19 2010-02-04 콘서트 파마슈티컬즈, 인크. 중수소화된 모르폴리닐 화합물
US7531685B2 (en) * 2007-06-01 2009-05-12 Protia, Llc Deuterium-enriched oxybutynin
US20090131485A1 (en) 2007-09-10 2009-05-21 Concert Pharmaceuticals, Inc. Deuterated pirfenidone
US20090118238A1 (en) 2007-09-17 2009-05-07 Protia, Llc Deuterium-enriched alendronate
US20090088416A1 (en) 2007-09-26 2009-04-02 Protia, Llc Deuterium-enriched lapaquistat
US20090082471A1 (en) 2007-09-26 2009-03-26 Protia, Llc Deuterium-enriched fingolimod
WO2009045476A1 (en) 2007-10-02 2009-04-09 Concert Pharmaceuticals, Inc. Pyrimidinedione derivatives
US20090105338A1 (en) 2007-10-18 2009-04-23 Protia, Llc Deuterium-enriched gabexate mesylate
WO2009051782A1 (en) 2007-10-18 2009-04-23 Concert Pharmaceuticals Inc. Deuterated etravirine
US20090131363A1 (en) 2007-10-26 2009-05-21 Harbeson Scott L Deuterated darunavir
NZ601350A (en) 2007-11-16 2013-08-30 Abbvie Inc Method of treating arthritis
US20100160322A1 (en) 2008-12-04 2010-06-24 Abbott Laboratories Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases
US8557983B2 (en) * 2008-12-04 2013-10-15 Abbvie Inc. Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases
UA108193C2 (uk) * 2008-12-04 2015-04-10 Апоптозіндукуючий засіб для лікування раку і імунних і аутоімунних захворювань
US8586754B2 (en) * 2008-12-05 2013-11-19 Abbvie Inc. BCL-2-selective apoptosis-inducing agents for the treatment of cancer and immune diseases
NZ592801A (en) 2008-12-05 2013-08-30 Abbvie Inc Sulfonamide derivatives as bcl-2-selective apoptosis-inducing agents for the treatment of cancer and immune diseases
US8563735B2 (en) 2008-12-05 2013-10-22 Abbvie Inc. Bcl-2-selective apoptosis-inducing agents for the treatment of cancer and immune diseases
CN102282128B (zh) 2009-01-19 2015-06-17 Abbvie公司 用于治疗癌症和免疫和自身免疫疾病的细胞程序死亡诱导药剂
HUE025527T2 (en) 2009-01-19 2016-04-28 Abbvie Inc Apoptosis inducers for the treatment of cancer, immune and autoimmune diseases
CN102448959B (zh) 2009-05-26 2015-06-17 艾伯维巴哈马有限公司 用于治疗癌症和免疫和自身免疫疾病的细胞程序死亡诱导药剂
US8546399B2 (en) 2009-05-26 2013-10-01 Abbvie Inc. Apoptosis inducing agents for the treatment of cancer and immune and autoimmune diseases
US9034875B2 (en) 2009-05-26 2015-05-19 Abbvie Inc. Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases

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