MA38961A1 - Composés 3-phenyl-1h-pyrazolo[3,4-d]pyrimidin-4-ylamine substitués inhibiteurs de la tyrosine kinase de bruton utilisés pour traiter par exemple les maladies auto-immunes, respiratoires et inflammatoires, cancer, mastocytose et osteoporose - Google Patents
Composés 3-phenyl-1h-pyrazolo[3,4-d]pyrimidin-4-ylamine substitués inhibiteurs de la tyrosine kinase de bruton utilisés pour traiter par exemple les maladies auto-immunes, respiratoires et inflammatoires, cancer, mastocytose et osteoporoseInfo
- Publication number
- MA38961A1 MA38961A1 MA38961A MA38961A MA38961A1 MA 38961 A1 MA38961 A1 MA 38961A1 MA 38961 A MA38961 A MA 38961A MA 38961 A MA38961 A MA 38961A MA 38961 A1 MA38961 A1 MA 38961A1
- Authority
- MA
- Morocco
- Prior art keywords
- cancer
- autoimmune
- tyrosine kinase
- inflammatory diseases
- mastocytosis
- Prior art date
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
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- 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
- A61K31/495—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
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/20—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
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- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0031—Rectum, anus
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K9/0048—Eye, e.g. artificial tears
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/007—Pulmonary tract; Aromatherapy
- A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
- A61K9/0078—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a nebulizer such as a jet nebulizer, ultrasonic nebulizer, e.g. in the form of aqueous drug solutions or dispersions
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
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- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4866—Organic macromolecular compounds
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
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- A—HUMAN NECESSITIES
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P35/04—Antineoplastic agents specific for metastasis
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
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- 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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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Dermatology (AREA)
- Immunology (AREA)
- Physical Education & Sports Medicine (AREA)
- Rheumatology (AREA)
- Pulmonology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Dispersion Chemistry (AREA)
- Oncology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Otolaryngology (AREA)
- Zoology (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Ophthalmology & Optometry (AREA)
- Pain & Pain Management (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
La présente invention concerne des composés qui forment des liaisons covalentes avec la tyrosine kinase de bruton (btk). L'invention concerne également des inhibiteurs irréversibles de btk. De plus, des inhibiteurs réversibles de btk sont également décrits. L'invention concerne également des compositions pharmaceutiques qui comprennent les composés. L'invention concerne de plus des procédés d'utilisation des inhibiteurs de btk, seuls ou en combinaison avec d'autres agents thérapeutiques, pour le traitement de maladies ou d'états auto-immuns, de maladies ou d'états hétéro-immuns, du cancer, comprenant un lymphome, et de maladies ou d'états inflammatoires.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201361884888P | 2013-09-30 | 2013-09-30 | |
PCT/US2014/058132 WO2015048689A1 (fr) | 2013-09-30 | 2014-09-29 | Inhibiteurs de la tyrosine kinase de bruton |
Publications (1)
Publication Number | Publication Date |
---|---|
MA38961A1 true MA38961A1 (fr) | 2018-05-31 |
Family
ID=52740746
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
MA38961A MA38961A1 (fr) | 2013-09-30 | 2014-09-29 | Composés 3-phenyl-1h-pyrazolo[3,4-d]pyrimidin-4-ylamine substitués inhibiteurs de la tyrosine kinase de bruton utilisés pour traiter par exemple les maladies auto-immunes, respiratoires et inflammatoires, cancer, mastocytose et osteoporose |
Country Status (20)
Country | Link |
---|---|
US (2) | US9624224B2 (fr) |
EP (1) | EP3052486A1 (fr) |
JP (1) | JP2016531941A (fr) |
KR (1) | KR20160062103A (fr) |
CN (1) | CN105764896A (fr) |
AR (1) | AR097862A1 (fr) |
AU (1) | AU2014324532A1 (fr) |
BR (1) | BR112016006978A2 (fr) |
CA (1) | CA2925124A1 (fr) |
CR (1) | CR20160203A (fr) |
DO (1) | DOP2016000071A (fr) |
EA (1) | EA201690618A1 (fr) |
IL (1) | IL244492A0 (fr) |
MA (1) | MA38961A1 (fr) |
PE (1) | PE20160560A1 (fr) |
PH (1) | PH12016500575A1 (fr) |
SG (1) | SG11201602421VA (fr) |
TN (1) | TN2016000094A1 (fr) |
TW (1) | TW201546061A (fr) |
WO (1) | WO2015048689A1 (fr) |
Families Citing this family (39)
Publication number | Priority date | Publication date | Assignee | Title |
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CA3113343A1 (fr) | 2010-06-03 | 2011-12-08 | Pharmacyclics Llc | Utilisation d'inhibiteurs de la tyrosine-kinase de bruton dans le traitement du lymphome folliculaire |
AU2012283775A1 (en) | 2011-07-13 | 2014-01-23 | Pharmacyclics Llc | Inhibitors of Bruton's tyrosine kinase |
WO2013013188A1 (fr) | 2011-07-21 | 2013-01-24 | Tolero Pharmaceuticals, Inc. | Inhibiteurs de protéine kinase hétérocycliques |
EP3550031A1 (fr) | 2012-07-24 | 2019-10-09 | Pharmacyclics, LLC | Mutations associées à la résistance aux inhibiteurs de la tyrosine kinase de bruton (btk) |
TR201911151T4 (tr) | 2013-03-14 | 2019-08-21 | Tolero Pharmaceuticals Inc | Jak2 ve alk2 inhibitörleri ve bunların kullanım yöntemleri. |
US9637487B2 (en) | 2013-07-02 | 2017-05-02 | Pharmacyclics Llc | Purinone compounds as kinase inhibitors |
WO2015143400A1 (fr) | 2014-03-20 | 2015-09-24 | Pharmacyclics, Inc. | Mutations de phospholipase c gamma 2 et associées aux résistances |
CN107021963A (zh) * | 2016-01-29 | 2017-08-08 | 北京诺诚健华医药科技有限公司 | 吡唑稠环类衍生物、其制备方法及其在治疗癌症、炎症和免疫性疾病上的应用 |
WO2017133630A1 (fr) * | 2016-02-05 | 2017-08-10 | 北京盛诺基医药科技有限公司 | Inhibiteur de la tyrosine kinase de bruton |
MA46995A (fr) | 2016-12-03 | 2019-10-09 | Acerta Pharma Bv | Méthodes et compositions pour l'utilisation de lymphocytes t thérapeutiques en association avec des inhibiteurs de kinase |
KR101956815B1 (ko) | 2017-02-14 | 2019-03-12 | 한국화학연구원 | 트리아졸로피리다진 유도체, 이의 제조방법 및 이를 유효성분으로 포함하는 브루톤티로신 키나제 활성 관련 질환의 예방 또는 치료용 약학적 조성물 |
JP2020508326A (ja) | 2017-02-24 | 2020-03-19 | ギリアド サイエンシズ, インコーポレイテッド | ブルトン型チロシンキナーゼの阻害剤 |
AR110998A1 (es) | 2017-02-24 | 2019-05-22 | Gilead Sciences Inc | Inhibidores de la tirosina cinasa de bruton |
CN108570036A (zh) * | 2017-03-09 | 2018-09-25 | 北京赛林泰医药技术有限公司 | 一种btk抑制剂的多晶型物及其制备方法 |
KR102128018B1 (ko) | 2017-05-12 | 2020-06-30 | 한국화학연구원 | 피라졸로 피리미딘 유도체, 이의 제조방법 및 이를 유효성분으로 함유하는 암, 자가면역질환 및 뇌질환의 예방 또는 치료용 약학적 조성물 |
WO2018208132A1 (fr) * | 2017-05-12 | 2018-11-15 | Korea Research Institute Of Chemical Technology | Dérivés de pyrazolopyrimidine, leur procédé de préparation et composition pharmaceutique pour utilisation dans la prévention ou le traitement du cancer, d'une maladie auto-immune et d'une maladie du cerveau contenant ceux-ci en tant que principe actif |
KR102032418B1 (ko) | 2017-06-15 | 2019-10-16 | 한국화학연구원 | 접합 피리미딘 유도체, 이의 제조방법 및 이를 유효성분으로 포함하는 브루톤티로신 키나제 활성 관련 질환의 예방 또는 치료용 약학적 조성물 |
CN109748929A (zh) * | 2017-11-06 | 2019-05-14 | 苏州鹏旭医药科技有限公司 | 一种化合物的制备方法 |
EP3706740A4 (fr) * | 2017-11-06 | 2021-07-28 | Suzhou Pengxu Pharmatech Co., Ltd. | Processus de production de l'acalabrutinib |
CN112533602A (zh) | 2018-04-05 | 2021-03-19 | 大日本住友制药肿瘤公司 | Axl激酶抑制剂及其用途 |
MX2020010556A (es) | 2018-04-13 | 2021-03-02 | Sumitomo Pharma Oncology Inc | Inhibidores de cinasa de insercion proviral en linfomas murinos (pim) para el tratamiento de neoplasias mieloproliferativas y fibrosis asociadas con cancer. |
CA3103995A1 (fr) | 2018-07-26 | 2020-01-30 | Sumitomo Dainippon Pharma Oncology, Inc. | Procedes de traitement de maladies associees a l'expression anormale d'acvr1 et inhibiteurs d'acvr1 destines a etre utilises dans ceux-ci |
CN110964016B (zh) * | 2018-09-29 | 2021-05-28 | 南京药捷安康生物科技有限公司 | 氨基降茨烷衍生物及其制备方法与应用 |
MX2021009371A (es) | 2019-02-12 | 2021-09-10 | Sumitomo Pharma Oncology Inc | Formulaciones que comprenden inhibidores de proteina cinasa heterociclicos. |
CN114364798A (zh) | 2019-03-21 | 2022-04-15 | 欧恩科斯欧公司 | 用于治疗癌症的Dbait分子与激酶抑制剂的组合 |
WO2020252397A1 (fr) * | 2019-06-12 | 2020-12-17 | Baylor College Of Medicine | Chimères ciblant la protéolyse à petites molécules et leurs méthodes d'utilisation |
CN111018865B (zh) * | 2019-10-17 | 2021-01-15 | 山东大学 | 1-取代苄基吡唑并嘧啶衍生物及其制备方法与应用 |
WO2021089791A1 (fr) | 2019-11-08 | 2021-05-14 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Méthodes pour le traitement de cancers qui ont acquis une résistance aux inhibiteurs de kinase |
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KR102637915B1 (ko) | 2021-06-25 | 2024-02-19 | 한국화학연구원 | 유비퀴틴 프로테오좀 경로를 통해 비티케이 분해작용을 가지는 신규한 이작용성 헤테로사이클릭 화합물과 이의 용도 |
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CN114213416B (zh) * | 2021-11-05 | 2023-06-06 | 杭州医学院 | 一种恶唑并[4,5-b]吡啶结构的不可逆BTK抑制剂及其应用 |
KR20240093556A (ko) | 2021-11-05 | 2024-06-24 | 주식회사 유빅스테라퓨틱스 | Btk 단백질 분해 활성을 갖는 화합물 및 이들의 의약 용도 |
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WO2024097653A1 (fr) | 2022-10-31 | 2024-05-10 | Sumitomo Pharma America, Inc. | Inhibiteur de pim-1 pour le traitement de néoplasmes myéloprolifératifs |
Family Cites Families (96)
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-
2014
- 2014-09-29 EA EA201690618A patent/EA201690618A1/ru unknown
- 2014-09-29 MA MA38961A patent/MA38961A1/fr unknown
- 2014-09-29 JP JP2016545269A patent/JP2016531941A/ja active Pending
- 2014-09-29 AU AU2014324532A patent/AU2014324532A1/en not_active Abandoned
- 2014-09-29 CA CA2925124A patent/CA2925124A1/fr not_active Abandoned
- 2014-09-29 CR CR20160203A patent/CR20160203A/es unknown
- 2014-09-29 US US14/500,897 patent/US9624224B2/en active Active
- 2014-09-29 CN CN201480065396.6A patent/CN105764896A/zh active Pending
- 2014-09-29 BR BR112016006978A patent/BR112016006978A2/pt not_active Application Discontinuation
- 2014-09-29 SG SG11201602421VA patent/SG11201602421VA/en unknown
- 2014-09-29 PE PE2016000427A patent/PE20160560A1/es not_active Application Discontinuation
- 2014-09-29 KR KR1020167010963A patent/KR20160062103A/ko not_active Application Discontinuation
- 2014-09-29 TN TN2016000094A patent/TN2016000094A1/en unknown
- 2014-09-29 WO PCT/US2014/058132 patent/WO2015048689A1/fr active Application Filing
- 2014-09-29 EP EP14848332.4A patent/EP3052486A1/fr not_active Withdrawn
- 2014-09-30 TW TW103134098A patent/TW201546061A/zh unknown
- 2014-09-30 AR ARP140103633A patent/AR097862A1/es unknown
-
2016
- 2016-03-08 IL IL244492A patent/IL244492A0/en unknown
- 2016-03-29 PH PH12016500575A patent/PH12016500575A1/en unknown
- 2016-03-29 DO DO2016000071A patent/DOP2016000071A/es unknown
- 2016-10-19 US US15/297,898 patent/US20170050970A1/en not_active Abandoned
Also Published As
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CA2925124A1 (fr) | 2015-04-02 |
JP2016531941A (ja) | 2016-10-13 |
US20170050970A1 (en) | 2017-02-23 |
DOP2016000071A (es) | 2016-09-15 |
BR112016006978A2 (pt) | 2017-08-01 |
PH12016500575A1 (en) | 2016-07-25 |
AU2014324532A1 (en) | 2016-04-21 |
IL244492A0 (en) | 2016-04-21 |
SG11201602421VA (en) | 2016-04-28 |
WO2015048689A1 (fr) | 2015-04-02 |
WO2015048689A8 (fr) | 2015-05-07 |
CR20160203A (es) | 2016-08-31 |
KR20160062103A (ko) | 2016-06-01 |
TN2016000094A1 (en) | 2017-07-05 |
US20150094319A1 (en) | 2015-04-02 |
CN105764896A (zh) | 2016-07-13 |
EP3052486A1 (fr) | 2016-08-10 |
TW201546061A (zh) | 2015-12-16 |
US9624224B2 (en) | 2017-04-18 |
EA201690618A1 (ru) | 2016-09-30 |
PE20160560A1 (es) | 2016-06-09 |
AR097862A1 (es) | 2016-04-20 |
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