KR20140117457A - Rtk 억제제와 항에스트로겐의 조합물 및 암의 치료를 위한 그의 용도 - Google Patents

Rtk 억제제와 항에스트로겐의 조합물 및 암의 치료를 위한 그의 용도 Download PDF

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Publication number: KR20140117457A
Authority: KR; South Korea
Prior art keywords: substituted; group; unsubstituted; compound; pharmaceutically acceptable
Prior art date: 2012-01-31
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.): Ceased

Application number

KR1020147021140A

Other languages

English (en)

Korean (ko)

Inventor

알레한드로 요바인

매튜 스퀴어스

캐서린 레딕

용 장

Original Assignee

노파르티스 아게

Priority date (The priority date 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 date listed.)

2012-01-31

Filing date

2013-01-30

Publication date

2014-10-07

2013-01-30 Application filed by 노파르티스 아게 filed Critical 노파르티스 아게

2014-10-07 Publication of KR20140117457A publication Critical patent/KR20140117457A/ko

Status Ceased legal-status Critical Current

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- A—HUMAN NECESSITIES
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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
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- A61K31/138—Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4535—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a heterocyclic ring having sulfur as a ring hetero atom, e.g. pizotifen
- A—HUMAN NECESSITIES
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- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A—HUMAN NECESSITIES
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- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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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Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Epidemiology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Organic Chemistry (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

KR1020147021140A 2012-01-31 2013-01-30 Rtk 억제제와 항에스트로겐의 조합물 및 암의 치료를 위한 그의 용도 Ceased KR20140117457A (ko)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US201261593047P	2012-01-31	2012-01-31
US61/593,047		2012-01-31
PCT/US2013/023781 WO2013116293A1 (en)	2012-01-31	2013-01-30	Combination of a rtk inhibitor with an anti - estrogen and use thereof for the treatment of cancer

Publications (1)

Publication Number	Publication Date
KR20140117457A true KR20140117457A (ko)	2014-10-07

Family

ID=47679114

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
KR1020147021140A Ceased KR20140117457A (ko)	2012-01-31	2013-01-30	Rtk 억제제와 항에스트로겐의 조합물 및 암의 치료를 위한 그의 용도

Country Status (12)

Country	Link
US (1)	US20140378422A1 (2)
EP (1)	EP2809312A1 (2)
JP (1)	JP2015505562A (2)
KR (1)	KR20140117457A (2)
CN (1)	CN104093402A (2)
AU (1)	AU2013215251A1 (2)
BR (1)	BR112014017985A8 (2)
CA (1)	CA2861377A1 (2)
IN (1)	IN2014DN05869A (2)
MX (1)	MX2014009303A (2)
RU (1)	RU2014135436A (2)
WO (1)	WO2013116293A1 (2)

Families Citing this family (15)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
WO2015136016A2 (en) *	2014-03-13	2015-09-17	F. Hoffmann-La Roche Ag	Therapeutic combinations with estrogen receptor modulators
EP3275442B1 (en)	2015-03-25	2021-07-28	National Cancer Center	Therapeutic agent for bile duct cancer
LT3386500T (lt)	2015-12-09	2022-12-27	The Board Of Trustees Of The University Of Illinois	Selektyvūs estrogenų receptorių slopintojai benzotiofeno pagrindu
CN108367000A (zh)	2015-12-17	2018-08-03	卫材R&D管理有限公司	用于乳腺癌的治疗剂
US11883404B2 (en)	2016-03-04	2024-01-30	Taiho Pharmaceuticals Co., Ltd.	Preparation and composition for treatment of malignant tumors
EP3424505A4 (en)	2016-03-04	2019-10-16	Taiho Pharmaceutical Co., Ltd.	PREPARATION AND COMPOSITION FOR THE TREATMENT OF MALIGNANT TUMORS
MX2019008158A (es)	2017-01-06	2019-12-09	G1 Therapeutics Inc	Terapia de combinacion para el tratamiento del cancer.
KR20190117582A (ko)	2017-02-10	2019-10-16	쥐원 쎄라퓨틱스, 인크.	벤조티오펜 에스트로겐 수용체 조정제
MA51570A (fr) *	2018-01-10	2020-11-18	Eisai R&D Man Co Ltd	Polythérapies pour le traitement du carcinome hépatocellulaire
JP6918204B2 (ja)	2018-03-19	2021-08-11	大鵬薬品工業株式会社	アルキル硫酸ナトリウムを含む医薬組成物
US11219619B2 (en)	2018-03-28	2022-01-11	Eisai R&D Management Co., Ltd.	Therapeutic agent for hepatocellular carcinoma
TWI841598B (zh) *	2018-09-13	2024-05-11	大陸商恒翼生物醫藥（上海）股份有限公司	用於治療雌激素受體陽性乳癌之組合療法
WO2020110974A1 (ja) *	2018-11-26	2020-06-04	大鵬薬品工業株式会社	線維芽細胞増殖因子受容体阻害剤と内分泌療法との併用による内分泌療法が適用される腫瘍の治療及び予防方法
AU2021315234A1 (en) *	2020-07-31	2023-01-19	Eisai R&D Management Co., Ltd.	Therapeutic agent for breast cancer
CN116940363A (zh) *	2021-03-03	2023-10-24	正大天晴药业集团股份有限公司	Cdk4/6抑制剂的联用药物组合物及其用途

Family Cites Families (16)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
BE637389A (2)	1962-09-13
US4418068A (en)	1981-04-03	1983-11-29	Eli Lilly And Company	Antiestrogenic and antiandrugenic benzothiophenes
GB2126576B (en)	1982-06-25	1985-06-19	Farmos Group Limited	Alkane and alkene derivatives
GB8327256D0 (en)	1983-10-12	1983-11-16	Ici Plc	Steroid derivatives
PT1107964E (pt)	1998-08-11	2010-06-11	Novartis Ag	Derivados de isoquinolina com actividade inibidora da angiogénese
DE60115069T2 (de)	2000-09-11	2006-08-03	Chiron Corp., Emeryville	Chinolinonderivate als tyrosin-kinase inhibitoren
US20030028018A1 (en)	2000-09-11	2003-02-06	Chiron Coporation	Quinolinone derivatives
ITTV20030095A1 (it)	2003-07-14	2005-01-15	Asolo Spa	Calzatura con sottopiede composito.
US20050209247A1 (en)	2003-11-07	2005-09-22	Chiron Corporation	Pharmaceutically acceptable salts of quinolinone compounds having improved pharmaceutical properties
EP2301546B1 (en) *	2005-01-27	2014-09-10	Novartis AG	Treatment of metastasized tumors
EP1885187B1 (en) *	2005-05-13	2013-09-25	Novartis AG	Methods for treating drug resistant cancer
BRPI0611375A2 (pt)	2005-05-23	2010-08-31	Novartis Ag	formas cristalinas e outras de sais de ácido láctico de 4-amino-5-flúor-3-[6-(4-metilpiperazin-1-il)-1h-benzimid azol-2-il]-1h-quinolin-2-ona
NZ567550A (en)	2005-11-29	2011-08-26	Novartis Ag	Formulations of lactic acid salts of 4-amino-5-fluoro-3-[6-(4-methyl-piperazin-1-yl)-1 H-benzimidazol-2-yl]1H-quinolin-2-one
US20080206194A1 (en) *	2007-02-16	2008-08-28	Glazer Robert I	Method for the treatment of breast cancer
PE20091628A1 (es)	2008-03-19	2009-11-19	Novartis Ag	Formas cristalinas y dos formas solvatadas de sales de acido lactico de 4-amino-5-fluoro-3-[5-(4-metilpiperazin-1-il)-1h-benzimidazol-2-il]quinolin-2(1h)-ona
AR081776A1 (es)	2010-06-30	2012-10-17	Novartis Ag	Composiciones farmaceuticas que comprenden monohidrato de lactato de 4-amino-5-fluoro-3-[6-(4-metil-piperazin-1-il)-1h-bencimidazol-2-il]-1h-quinolin-2-ona, proceso para la produccion de la composicion

2013
- 2013-01-30 EP EP13703295.9A patent/EP2809312A1/en not_active Withdrawn
- 2013-01-30 MX MX2014009303A patent/MX2014009303A/es unknown
- 2013-01-30 AU AU2013215251A patent/AU2013215251A1/en not_active Abandoned
- 2013-01-30 KR KR1020147021140A patent/KR20140117457A/ko not_active Ceased
- 2013-01-30 CN CN201380006947.7A patent/CN104093402A/zh active Pending
- 2013-01-30 US US14/375,145 patent/US20140378422A1/en not_active Abandoned
- 2013-01-30 WO PCT/US2013/023781 patent/WO2013116293A1/en not_active Ceased
- 2013-01-30 CA CA2861377A patent/CA2861377A1/en not_active Abandoned
- 2013-01-30 BR BR112014017985A patent/BR112014017985A8/pt not_active Application Discontinuation
- 2013-01-30 RU RU2014135436A patent/RU2014135436A/ru unknown
- 2013-01-30 JP JP2014555661A patent/JP2015505562A/ja active Pending
- 2013-01-30 IN IN5869DEN2014 patent/IN2014DN05869A/en unknown

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Publication number	Publication date
BR112014017985A2 (2)	2017-06-20
RU2014135436A (ru)	2016-03-27
MX2014009303A (es)	2014-10-14
AU2013215251A1 (en)	2014-08-14
WO2013116293A1 (en)	2013-08-08
IN2014DN05869A (2)	2015-05-22
EP2809312A1 (en)	2014-12-10
US20140378422A1 (en)	2014-12-25
JP2015505562A (ja)	2015-02-23
BR112014017985A8 (pt)	2017-07-11
CN104093402A (zh)	2014-10-08
CA2861377A1 (en)	2013-08-08

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2014-07-28	PA0105	International application	Patent event date: 20140728 Patent event code: PA01051R01D Comment text: International Patent Application
2014-10-07	PG1501	Laying open of application
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Publication	Publication Date	Title
KR20140117457A (ko)	2014-10-07	Rtk 억제제와 항에스트로겐의 조합물 및 암의 치료를 위한 그의 용도
US9421208B2 (en)	2016-08-23	Methods for the treatment of solid tumors
JP6180420B2 (ja)	2017-08-16	増殖性疾患の治療のためのｈｓｐ９０阻害剤と組み合わせた２−カルボキサミドシクロアミノウレア誘導体
KR20190021355A (ko)	2019-03-05	Ar+ 유방암 치료 방법
US9682082B2 (en)	2017-06-20	Combinations of AKT and MEK inhibitor compounds, and methods of use
AU2018202898A1 (en)	2018-05-17	Therapeutics targeting truncated Adenomatous Polyposis Coli (APC) proteins
CA3103995A1 (en)	2020-01-30	Methods for treating diseases associated with abnormal acvr1 expression and acvr1 inhibitors for use in the same
CA2608171C (en)	2014-02-04	Use of quinolinone compounds for treating drug resistant cancers
CN106243096B (zh)	2019-11-29	三环类药物的新用途
US9669004B2 (en)	2017-06-06	Daidzein analogs as treatment for cancer
JP6212563B2 (ja)	2017-10-11	ホスファチジルイノシトール３−キナーゼ阻害剤およびアロマターゼ阻害剤を含む組合せ医薬
KR20230116950A (ko)	2023-08-04	불안 장애를 치료하기 위한 (2S)-1-[4-(3,4-디클로로페닐)피페리딘-1-일]-3-[2-(5-메틸-1,3,4-옥사디아졸-2-일)벤조[b]푸란-4-일옥시]프로판-2-올또는 그의 대사산물
TW201420102A (zh)	2014-06-01	組合療法
HK1110477B (en)	2014-03-14	Methods for treating drug resistant cancer
NZ617243B2 (en)	2016-05-27	Combinations of akt and mek inhibitor compounds, and methods of use