UA121021C2 - Терапевтично активні сполуки і способи їх застосування - Google Patents

Терапевтично активні сполуки і способи їх застосування Download PDF

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Publication number: UA121021C2
Authority: UA; Ukraine
Prior art keywords: compound; dose; profile; temperature; treatment
Prior art date: 2013-08-02

Application number

UAA201601999A

Other languages

English (en)

Ukrainian (uk)

Inventor

Семюел В. Агреста

Чун-Хой ГУ

Девід Шенкейн

Девид Шенкейн

Хуа ЯН

Літін Го

Литин Го

Чжень Тан

Цзяньмін Ван

Цзяньмин Ван

Яньфен Чжан

Янь ЧЖОУ

Original Assignee

Аджіос Фармасьютікалз, Інк.

Аджиос Фармасьютикалз, Инк.

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.)

2013-08-02

Filing date

2014-08-01

Publication date

2020-03-25

2013-08-09 Priority claimed from PCT/CN2013/081170 external-priority patent/WO2015018060A1/en

2014-08-01 Application filed by Аджіос Фармасьютікалз, Інк., Аджиос Фармасьютикалз, Инк. filed Critical Аджіос Фармасьютікалз, Інк.

2020-03-25 Publication of UA121021C2 publication Critical patent/UA121021C2/uk

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Classifications

- 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
- 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
- A61K31/435—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
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
- 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
- A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Animal Behavior & Ethology (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Medicinal Chemistry (AREA)
General Health & Medical Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Organic Chemistry (AREA)
Epidemiology (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Bioinformatics & Cheminformatics (AREA)
Physical Education & Sports Medicine (AREA)
Engineering & Computer Science (AREA)
Neurology (AREA)
Hematology (AREA)
Orthopedic Medicine & Surgery (AREA)
Oncology (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)
Plural Heterocyclic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Medicinal Preparation (AREA)

UAA201601999A 2013-08-02 2014-08-01 Терапевтично активні сполуки і способи їх застосування UA121021C2 (uk)

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US201361861884P	2013-08-02	2013-08-02
PCT/CN2013/081170 WO2015018060A1 (en)	2013-08-09	2013-08-09	Crystalline forms of therapeutically active compounds and use thereof
US201461939098P	2014-02-12	2014-02-12
US201461975448P	2014-04-04	2014-04-04
US201462011948P	2014-06-13	2014-06-13
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CN (3)	CN110372670B (2)
AU (2)	AU2014295938B2 (2)
BR (1)	BR112016002287A2 (2)
CA (1)	CA2919382A1 (2)
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IL (2)	IL243833A0 (2)
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WO2015003360A2 (en)	2013-07-11	2015-01-15	Agios Pharmaceuticals, Inc.	Therapeutically active compounds and their methods of use
AU2014295938B2 (en) *	2013-08-02	2018-07-19	Les Laboratoires Servier	Therapeutically active compounds and their methods of use
JP2017529382A (ja) *	2014-09-29	2017-10-05	アギオスファーマシューティカルス，インコーポレーテッド	治療活性を有する化合物及びその使用方法
JP7220986B6 (ja)	2015-02-04	2024-02-08	アジオスファーマシューティカルズ，インコーポレイテッド	治療効果のある化合物及びその使用方法
CN107922354B (zh) *	2015-05-07	2021-05-25	苏州韬略生物科技有限公司	作为idh2抑制剂的杂环化合物
DK3330258T3 (da) *	2015-07-30	2021-08-16	Chia Tai Tianqing Pharmaceutical Group Co Ltd	1, 3, 5-triazinderivat og fremgangsmåde til anvendelse af samme
US9751863B2 (en)	2015-08-05	2017-09-05	Agios Pharmaceuticals, Inc.	Therapeutically active compounds and their methods of use
US10695352B2 (en) *	2015-10-15	2020-06-30	Celgene Corporation	Combination therapy for treating malignancies
KR20180063125A (ko)	2015-10-15	2018-06-11	아지오스 파마슈티컬스 아이엔씨.	악성종양을 치료하기 위한 복합 요법
CA3002531C (en) *	2015-10-21	2020-08-18	NeuForm Pharmaceuticals, Inc.	Deuterated compounds for treating hematologic malignancies, and compositions and methods thereof
ES2905915T3 (es)	2015-12-04	2022-04-12	Servier Lab	Procedimientos de tratamiento de neoplasias malignas
WO2017140758A1 (en)	2016-02-19	2017-08-24	Debiopharm International S.A.	Derivatives of 2-amino-4-(2-oxazolidinon-3-yl)-pyrimidine fused with a five-membered heteroaromatic ring in 5,6-position which are useful for the treatment of various cancers
MA43640A (fr) *	2016-02-26	2018-11-28	Agios Pharmaceuticals Inc	Inhibiteurs de idh1 pour le traitement de cancers hématologiques et de tumeurs solides
EP3493809B1 (en)	2016-08-03	2023-08-23	Celgene Corporation	Enasidenib for treatment of myelodysplastic syndrome
JP7093764B2 (ja) *	2016-08-03	2022-06-30	セルジーンコーポレイション	骨髄異形成症候群の治療方法
MX392941B (es)	2016-09-07	2025-03-24	Celgene Corp	Composiciones para comprimidos.
ES2924500T3 (es) *	2017-01-22	2022-10-07	Chia Tai Tianqing Pharmaceutical Group Co Ltd	Sal de derivado de 1,3,5-triazina, cristal, método de preparación, composición farmacéutica y uso de la misma
WO2018204787A1 (en)	2017-05-05	2018-11-08	Memorial Sloan Kettering Cancer Center	Methods of treatment of myeloproliferative neoplasm
KR20200020899A (ko)	2017-06-30	2020-02-26	셀진 코포레이션	2-(4-클로로페닐)-n-((2-(2,6-디옥소피페리딘-3-일)-1-옥소이소인돌린-5-일)메틸)-2,2-디플루오로아세트아미드의 조성물 및 사용 방법
CN109467538A (zh)	2017-09-07	2019-03-15	和记黄埔医药（上海）有限公司	环烯烃取代的杂芳环类化合物及其用途
WO2020092894A1 (en)	2018-11-02	2020-05-07	Celgene Corporation	Solid forms of 2-methyl-1-[(4-[6-(trifluoromethyl) pyridin-2-yl]-6-{[2-(trifluoromethyl)pyridin-4-yl]amino}-1,3,5-triazin-2-yl) amino]propan-2-ol
US20220017489A1 (en)	2018-11-02	2022-01-20	Celgene Corporation	Solid dispersions for treatment of cancer
US20220017490A1 (en)	2018-11-02	2022-01-20	Celgene Corporation	Co-crystals of 2-methyl-1 -[(4-[6-(trifluoromethyl)pyridin-2-yl]-6-{[2-(trifluoromethyl) pyridin-4-yl]amino}-1,3,5-triazin-2-yl)amino]propan-2-ol, compositions and methods of use thereof
JP2023503842A (ja)	2019-11-14	2023-02-01	セルジーンコーポレーション	がんを処置するための小児用製剤
CN114773320A (zh) *	2022-05-29	2022-07-22	重庆医科大学	1,3,5-三嗪化合物及其制备方法和用途

Family Cites Families (19)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US2390529A (en)	1942-02-03	1945-12-11	Ernst A H Friedheim	Hydrazino-1,3,5-triazino derivatives of substituted phenylarsenic compounds
JPS58186682A (ja)	1982-04-27	1983-10-31	日本化薬株式会社	セルロ−ス又はセルロ−ス含有繊維材料の染色法
DE3512630A1 (de)	1985-04-06	1986-10-23	Hoechst Ag, 6230 Frankfurt	Verfahren zum faerben oder bedrucken von cellulosefasern oder cellulosemischfasern
DE59106971D1 (de)	1990-07-12	1996-01-11	Ciba Geigy Ag	Verfahren zur photochemischen und thermischen Stabilisierung von Polyamid-Fasermaterialien.
JPH11158073A (ja)	1997-09-26	1999-06-15	Takeda Chem Ind Ltd	アデノシンａ３拮抗剤
AU5379900A (en)	1999-06-07	2000-12-28	Shire Biochem Inc.	Thiophene integrin inhibitors
WO2003037346A1 (en) *	2001-10-31	2003-05-08	Cell Therapeutics, Inc.	6-phenyl-n-phenyl-(1,3,5) -triazine-2,4-diamine derivatives and related compounds with lysophphosphatidic acid acyltransferase beta (lpaat-beta) inhibitory activity for use in the treatment of cancer
EP2256108B1 (en)	2002-07-18	2016-03-23	Janssen Pharmaceutica NV	Substituted triazine kinase inhibitors
JP5450381B2 (ja) *	2007-04-30	2014-03-26	プロメティック・バイオサイエンスィズ・インコーポレーテッド	化合物、そのような化合物を含有する組成物、及びそのような化合物を用いるがん及び自己免疫疾患の治療法
GB0805477D0 (en)	2008-03-26	2008-04-30	Univ Nottingham	Pyrimidines triazines and their use as pharmaceutical agents
WO2010144338A1 (en)	2009-06-08	2010-12-16	Abraxis Bioscience, Llc	Triazine derivatives and their therapeutical applications
CA2767008C (en) *	2009-07-07	2018-01-30	Pathway Therapeutics, Inc.	Pyrimidinyl and 1,3,5-triazinyl benzimidazoles and their use in cancer therapy
PE20142098A1 (es) *	2012-01-06	2015-01-08	Agios Pharmaceuticals Inc	Compuestos terapeuticamente activos y sus metodos de uso
KR20140131955A (ko)	2012-03-09	2014-11-14	카나 바이오사이언스 인코포레이션	신규 트리아진 유도체
WO2015003360A2 (en)	2013-07-11	2015-01-15	Agios Pharmaceuticals, Inc.	Therapeutically active compounds and their methods of use
AU2014287122B9 (en)	2013-07-11	2018-11-01	Les Laboratoires Servier	N,6-bis(aryl or heteroaryl)-1,3,5-triazine-2,4-diamine compounds as IDH2 mutants inhibitors for the treatment of cancer
AU2014295938B2 (en) *	2013-08-02	2018-07-19	Les Laboratoires Servier	Therapeutically active compounds and their methods of use
JP2017529382A (ja)	2014-09-29	2017-10-05	アギオスファーマシューティカルス，インコーポレーテッド	治療活性を有する化合物及びその使用方法
JP7220986B6 (ja)	2015-02-04	2024-02-08	アジオスファーマシューティカルズ，インコーポレイテッド	治療効果のある化合物及びその使用方法

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CN110386922A (zh)	2019-10-29
NZ716226A (en)	2021-08-27
NI201600022A (es)	2016-03-16
US20240132474A1 (en)	2024-04-25
CN105916507A (zh)	2016-08-31
TW201524971A (zh)	2015-07-01
TWI666208B (zh)	2019-07-21
US20170305885A1 (en)	2017-10-26
IL270347B (en)	2021-08-31
AU2014295938B2 (en)	2018-07-19
PH12016500164A1 (en)	2016-04-25
US20160194305A1 (en)	2016-07-07
CL2017002240A1 (es)	2018-04-20
MX394658B (es)	2025-03-24
US20210155603A1 (en)	2021-05-27
CA2919382A1 (en)	2015-02-05
EA030428B1 (ru)	2018-08-31
JP2021176893A (ja)	2021-11-11
MY177994A (en)	2020-09-28
WO2015017821A2 (en)	2015-02-05
PE20160840A1 (es)	2016-09-22
CN110372670A (zh)	2019-10-25
EP3566706A1 (en)	2019-11-13
EP3932408A1 (en)	2022-01-05
ES2886211T3 (es)	2021-12-16
JP2016527279A (ja)	2016-09-08
MX2016001361A (es)	2016-06-14
MX389250B (es)	2025-03-20
AU2018247242A1 (en)	2018-11-01
AU2018247242B2 (en)	2020-03-12
US9738625B2 (en)	2017-08-22
BR112016002287A2 (pt)	2017-08-01
SG10201709187TA (en)	2017-12-28
TWI701242B (zh)	2020-08-11
CL2016000263A1 (es)	2016-08-19
SA516370523B1 (ar)	2019-01-10
IL243833A0 (en)	2016-04-21
CN110372670B (zh)	2023-04-07
EP3566706B1 (en)	2021-07-14
US20260085059A1 (en)	2026-03-26
EA201690322A1 (ru)	2016-07-29
EP3027193A2 (en)	2016-06-08
AU2014295938A1 (en)	2016-02-18
PH12016500164B1 (en)	2023-11-08
JP2019142930A (ja)	2019-08-29
TW201932455A (zh)	2019-08-16
US10730854B2 (en)	2020-08-04
SG11201600479WA (en)	2016-02-26
JP6742905B2 (ja)	2020-08-19
EP3027193A4 (en)	2017-04-26
US10093654B2 (en)	2018-10-09
MX2020011397A (es)	2022-08-05
WO2015017821A3 (en)	2015-04-09
US20180370951A1 (en)	2018-12-27

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UA121021C2 (uk)	2020-03-25	Терапевтично активні сполуки і способи їх застосування
JP2023011792A (ja)	2023-01-24	治療効果のある化合物及びその使用方法
JP2020147571A (ja)	2020-09-17	治療活性を有する化合物及びその使用方法
HK40016189B (en)	2023-06-23	Therapeutically active compounds and their methods of use
HK40016190A (en)	2020-09-11	Therapeutically active compounds and their methods of use
HK40016189A (en)	2020-09-11	Therapeutically active compounds and their methods of use
HK40016900B (en)	2022-04-29	Therapeutically active compounds and their methods of use
HK40016900A (en)	2020-09-18	Therapeutically active compounds and their methods of use
NZ716226B2 (en)	2021-11-30	Therapeutically active compounds and their methods of use