MA33614B1 - Composés de benzoxépine inhibiteurs de pi3k et leurs procédés d'utilisation - Google Patents

Composés de benzoxépine inhibiteurs de pi3k et leurs procédés d'utilisation

Info

Publication number
MA33614B1
MA33614B1 MA34727A MA34727A MA33614B1 MA 33614 B1 MA33614 B1 MA 33614B1 MA 34727 A MA34727 A MA 34727A MA 34727 A MA34727 A MA 34727A MA 33614 B1 MA33614 B1 MA 33614B1
Authority
MA
Morocco
Prior art keywords
methods
formula
benzoxin
combinations
pi3k inhibitors
Prior art date
Application number
MA34727A
Other languages
Arabic (ar)
English (en)
Inventor
Nicole Blaquiere
Steven Do
Danette Dudley
Adrian J Folkes
Richard A Goldsmith
Robert Heald
Tim Heffron
Aleksandr Kolesnikov
Chudi Ndubaku
Alan G Olivero
Stephen Price
Steven Staben
Binqing Wei
Original Assignee
Hoffmann La Roche
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.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=43125543&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=MA33614(B1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Hoffmann La Roche filed Critical Hoffmann La Roche
Publication of MA33614B1 publication Critical patent/MA33614B1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
    • C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
    • C07D513/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D495/04—Ortho-condensed systems
    • 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
    • A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
    • A61K31/381—Heterocyclic compounds having sulfur as a ring hetero atom having five-membered rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A—HUMAN NECESSITIES
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    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4196—1,2,4-Triazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4245—Oxadiazoles
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    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A61K31/429—Thiazoles condensed with heterocyclic ring systems
    • A—HUMAN NECESSITIES
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    • 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
    • A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/4365—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system having sulfur as a ring hetero atom, e.g. ticlopidine
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    • 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
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
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    • 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
    • A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
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    • 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
    • A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • 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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    • A61K31/33—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
    • A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • 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
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    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/54—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 sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/541—Non-condensed thiazines containing further heterocyclic rings
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    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
    • A—HUMAN NECESSITIES
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    • A—HUMAN NECESSITIES
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    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
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    • C—CHEMISTRY; METALLURGY
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    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
    • C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
    • C07D249/10—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D249/14—Nitrogen atoms
    • C—CHEMISTRY; METALLURGY
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    • C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
    • C07D495/14—Ortho-condensed systems
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    • C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
    • C07D513/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains three hetero rings
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    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
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  • Epidemiology (AREA)
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  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Oncology (AREA)
  • Virology (AREA)
  • Emergency Medicine (AREA)
  • Communicable Diseases (AREA)
  • Biochemistry (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Molecular Biology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Endocrinology (AREA)
  • Obesity (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

L'INVENTION PORTE SUR DES COMPOSÉS DE BENZOXÉPINE DE FORMULE I, Y COMPRIS LES STÉRÉOISOMÈRES, ISOMÈRES GÉOMÉTRIQUES, TAUTOMÈRES, SOLVATES, MÉTABOLITES ET SELS PHARMACEUTIQUEMENT ACCEPTABLES DE CEUX-CI, DANS LAQUELLE FORMULE : Z1 REPRÉSENTE CR1 OU N; Z2 REPRÉSENTE CR2 OU N; Z3 REPRÉSENTE CR3 OU N; Z4 REPRÉSENTE CR4 OU N; ET DANS LAQUELLE (I) X1 REPRÉSENTE N ET X2 REPRÉSENTE S, (II) X1 REPRÉSENTE S ET X2 REPRÉSENTE N, (III) X1 REPRÉSENTE CR7 ET X2 REPRÉSENTE S, (IV) X1 REPRÉSENTE S ET X2 REPRÉSENTE CR7; (V) X1 REPRÉSENTE NR8 ET X2 REPRÉSENTE N, (VI) X1 REPRÉSENTE N ET X2 REPRÉSENTE NR8, (VII) X1 REPRÉSENTE CR7 ET X2 REPRÉSENTE O, (VIII) X1 REPRÉSENTE O ET X2 REPRÉSENTE CR7, (IX) X1 REPRÉSENTE CR7 ET X2 REPRÉSENTE C(R7)2, (X) X1 REPRÉSENTE C(R7)2 ET X2 REPRÉSENTE CR7; (XI) X1 REPRÉSENTE N ET X2 REPRÉSENTE O OU (XII) X1 REPRÉSENTE O ET X2 REPRÉSENTE N, LESQUELS SONT UTILES POUR L'INHIBITION DE LIPIDE-KINASES, DONT LA P110-ALPHA ET D'AUTRES ISOFORMES DE PI3K, ET POUR LE TRAITEMENT DE TROUBLES TELS QU'UN CANCER À MÉDIATION PAR DES LIPIDE-KINASES. L'INVENTION PORTE ÉGALEMENT SUR DES PROCÉDÉS D'UTILISATION DE COMPOSÉS DE FORMULE I POUR LE DIAGNOSTIC IN VITRO, IN SITU ET IN VIVO, LA PRÉVENTION OU LE TRAITEMENT DE TELS TROUBLES DANS DES CELLULES DE MAMMIFÈRE, OU D'ÉTATS PATHOLOGIQUES ASSOCIÉS.
MA34727A 2009-09-28 2012-03-28 Composés de benzoxépine inhibiteurs de pi3k et leurs procédés d'utilisation MA33614B1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US24638609P 2009-09-28 2009-09-28
PCT/EP2010/064222 WO2011036284A1 (fr) 2009-09-28 2010-09-27 Composés de benzoxépine inhibiteurs de pi3k et leurs procédés d'utilisation

Publications (1)

Publication Number Publication Date
MA33614B1 true MA33614B1 (fr) 2012-09-01

Family

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MA34727A MA33614B1 (fr) 2009-09-28 2012-03-28 Composés de benzoxépine inhibiteurs de pi3k et leurs procédés d'utilisation

Country Status (24)

Country Link
US (4) US8263633B2 (fr)
EP (2) EP2483277B1 (fr)
JP (2) JP5546636B2 (fr)
KR (2) KR20140034948A (fr)
CN (2) CN104987345A (fr)
AU (1) AU2010299820A1 (fr)
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Families Citing this family (31)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SG10201407781SA (en) * 2009-09-28 2015-01-29 Hoffmann La Roche Benzoxepin PI3K Inhibitor Compounds And Methods Of Use
RS53164B (en) * 2009-09-28 2014-06-30 F. Hoffmann-La Roche Ag BENZOXAZEPINE PI3K INHIBITOR COMPOUNDS AND THEIR USE IN CANCER TREATMENT
CA2825966A1 (fr) 2011-03-21 2012-09-27 F. Hoffmann-La Roche Ag Composes de benzoxazepine selectifs pour pi3k p110 delta et leurs methodes d'utilisation
WO2013030750A1 (fr) 2011-09-01 2013-03-07 Lupin Limited Composés antiviraux
JP2015507001A (ja) 2012-02-17 2015-03-05 エフ．ホフマン−ラ ロシュ アーゲーＦ． Ｈｏｆｆｍａｎｎ−Ｌａ Ｒｏｃｈｅ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ 三環式化合物及びその使用方法
KR20160027219A (ko) 2012-05-23 2016-03-09 에프. 호프만-라 로슈 아게 내배엽 및 간세포를 수득하고 사용하는 조성물 및 방법
AU2013273489B9 (en) 2012-06-08 2018-08-23 F. Hoffmann-La Roche Ag Mutant selectivity and combinations of a phosphoinositide 3 Kinase inhibitor compound and chemotherapeutic agents for the treatment of cancer
CN104640858B (zh) 2012-09-26 2018-11-06 霍夫曼-拉罗奇有限公司 环醚吡唑-4-基-杂环基-甲酰胺化合物及使用方法
RS59411B1 (sr) 2013-03-13 2019-11-29 Forma Therapeutics Inc Derivati 2-hidroksi-1-{4-[(4-fenilfenil)karbonil]piperazin-1-il}etan-1-ona i srodna jedinjenja kao inhibitori sintaze masnih kiselina (fasn) za lečenje kancera
CA3005103A1 (fr) 2013-03-13 2014-09-18 F. Hoffmann-La Roche Ag Procede de fabrication de composes benzoazepines
CN103274963B (zh) * 2013-06-28 2015-12-23 江苏倍达医药科技有限公司 一种合成1，1，1-三氟异丙基肼盐酸盐的方法
CN106659765B (zh) 2014-04-04 2021-08-13 德玛医药 二脱水半乳糖醇及其类似物或衍生物用于治疗非小细胞肺癌和卵巢癌的用途
NO2714752T3 (fr) * 2014-05-08 2018-04-21
JP6668362B2 (ja) 2015-02-02 2020-03-18 フォーマ セラピューティクス，インコーポレイテッド Ｈｄａｃ阻害薬としての３−アルキル−４−アミド−二環式［４，５，０］ヒドロキサム酸
AR103598A1 (es) 2015-02-02 2017-05-24 Forma Therapeutics Inc Ácidos bicíclicos[4,6,0]hidroxámicos como inhibidores de hdac
RU2571094C1 (ru) * 2015-02-11 2015-12-20 Федеральное государственное бюджетное образовательное учреждение высшего профессионального образования "Омский государственный университет им. Ф.М. Достоевского" СПОСОБ ПОЛУЧЕНИЯ 4-АЛКОКСИ-4Н-ТИЕНО[3,2-с]ХРОМЕН-2-КАРБАЛЬДЕГИДОВ, ОБЛАДАЮЩИХ ПРОТИВОЯЗВЕННОЙ АКТИВНОСТЬЮ
US20180214452A1 (en) 2015-03-06 2018-08-02 Korea Advanced Institute Of Science And Technology COMPOSITION FOR PREVENTION OR TREATMENT OF INTRACTABLE EPILEPSY COMPRISING mTOR INHIBITOR
CN107995911B (zh) * 2015-07-02 2020-08-04 豪夫迈·罗氏有限公司 苯并氧氮杂*噁唑烷酮化合物及其使用方法
AR105238A1 (es) 2015-07-02 2017-09-20 Hoffmann La Roche Compuestos de benzoxacepina oxazolidinona y métodos de uso
CN112409378A (zh) * 2015-09-08 2021-02-26 豪夫迈·罗氏有限公司 三环pi3k抑制剂化合物及其使用方法
PL3347356T3 (pl) 2015-09-09 2021-08-16 Jubilant Biosys Limited Trójpierścieniowe zespolone pochodne pirydyn-2-onu i ich zastosowanie jako inhibitorów brd4
US10241701B2 (en) * 2015-09-16 2019-03-26 Samsung Electronics Co., Ltd. Solid state memory system with power management mechanism and method of operation thereof
GB201516504D0 (en) 2015-09-17 2015-11-04 Astrazeneca Ab Imadazo(4,5-c)quinolin-2-one Compounds and their use in treating cancer
US10555935B2 (en) 2016-06-17 2020-02-11 Forma Therapeutics, Inc. 2-spiro-5- and 6-hydroxamic acid indanes as HDAC inhibitors
CN106317050B (zh) * 2016-08-24 2018-11-23 烟台大学 一种苯基噻唑衍生物及其制备方法与应用
TW201825465A (zh) 2016-09-23 2018-07-16 美商基利科學股份有限公司 磷脂醯肌醇3-激酶抑制劑
TW201815787A (zh) 2016-09-23 2018-05-01 美商基利科學股份有限公司 磷脂醯肌醇3-激酶抑制劑
TW201813963A (zh) 2016-09-23 2018-04-16 美商基利科學股份有限公司 磷脂醯肌醇3-激酶抑制劑
TWI767148B (zh) 2018-10-10 2022-06-11 美商弗瑪治療公司 抑制脂肪酸合成酶(fasn)
WO2020092395A1 (fr) 2018-10-29 2020-05-07 Forma Therapeutics, Inc. Formes solides de (4-(2-fluoro-4-(1-méthyl-1h-benzo[d]imidazol-5-yl)benzoyl)pipérazin-1-yl)(1-hydroxycyclopropyl)méthanone
US20230174549A1 (en) * 2020-05-11 2023-06-08 University Health Network Salt and crystal forms of 4-amino-5-(6-(4-methylpiperazin-1-yl)-1h-benzo[d]imidazol-2-yl)thieno[2,3-b]pyridin-6(7h)-one

Family Cites Families (54)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3773919A (en) 1969-10-23 1973-11-20 Du Pont Polylactide-drug mixtures
GB8504702D0 (en) * 1985-02-23 1985-03-27 Zyma Sa Tricyclic compounds
US5583024A (en) 1985-12-02 1996-12-10 The Regents Of The University Of California Recombinant expression of Coleoptera luciferase
FR2677356B1 (fr) * 1991-06-05 1995-03-17 Sanofi Sa Derives heterocycliques d'acylamino-2 thiazoles-5 substitues, leur preparation et compositions pharmaceutiques en contenant.
US5846824A (en) 1994-02-07 1998-12-08 Ludwig Institute For Cancer Research Polypeptides having kinase activity, their preparation and use
GB9208135D0 (en) 1992-04-13 1992-05-27 Ludwig Inst Cancer Res Polypeptides having kinase activity,their preparation and use
US6274327B1 (en) 1992-04-13 2001-08-14 Ludwig Institute For Cancer Research Polypeptides having kinase activity, their preparation and use
DK0638071T3 (da) * 1992-12-28 1997-10-27 Eisai Co Ltd Heterocykliske carboxylsyrederivater, der bindes til retenoidreceptorer (RAR)
US5543523A (en) 1994-11-15 1996-08-06 Regents Of The University Of Minnesota Method and intermediates for the synthesis of korupensamines
JPH08175990A (ja) 1994-12-19 1996-07-09 Mitsubishi Chem Corp Ｐｉ３キナーゼ阻害剤とその製造法
JPH08176070A (ja) 1994-12-19 1996-07-09 Mitsubishi Chem Corp ジデプシド誘導体及びｐｉ３キナーゼ阻害剤
JPH08336393A (ja) 1995-04-13 1996-12-24 Mitsubishi Chem Corp 光学活性なγ−置換−β−ヒドロキシ酪酸エステルの製造法
GB9521987D0 (en) 1995-10-26 1996-01-03 Ludwig Inst Cancer Res Phosphoinositide 3-kinase modulators
US5985799A (en) * 1995-11-17 1999-11-16 E.I. Du Pont De Nemours And Company Tricyclic herbicidal heterocycles
US6602677B1 (en) 1997-09-19 2003-08-05 Promega Corporation Thermostable luciferases and methods of production
DE19908535A1 (de) * 1999-02-26 2000-08-31 Aventis Pharma Gmbh Verwendung von polycyclischen Thiazol-Systemen zur Herstellung von Medikamenten zur Prophylaxe oder Behandlung von Obesitas
DE19908533A1 (de) * 1999-02-26 2000-08-31 Aventis Pharma Gmbh Polycyclische Thiazol-Systeme, Verfahren zu ihrer Herstellung und Arzneimittel enthaltend diese Verbindungen
DE19908538A1 (de) * 1999-02-26 2000-08-31 Aventis Pharma Gmbh Polycyclische 2-Amino-Thiazol Systeme, Verfahren zu ihrer Herstellung und Arzneimittel enthaltend diese Verbindungen
DE19908537A1 (de) * 1999-02-26 2000-08-31 Aventis Pharma Gmbh Verwendung von polycyclischen 2-Amino-Thiazol Systemen zur Herstellung von Medikamenten zur Prophylaxe oder Behandlung von Obesitas
US7273880B2 (en) * 1999-06-30 2007-09-25 H. Lunbeck A/S Selective NPY (Y5) antagonists
EP1204654B1 (fr) 1999-07-29 2003-07-23 Eli Lilly And Company Benzofurylpiperazines: agonistes du recepteur 5-ht2c de la serotonine
JP2001247477A (ja) 2000-03-03 2001-09-11 Teikoku Hormone Mfg Co Ltd 抗腫瘍剤
AU2001246494A1 (en) * 2000-03-03 2001-09-12 Novartis Ag Condensed thiazolamines and their use as neuropeptide y5 antagonists
US6608053B2 (en) 2000-04-27 2003-08-19 Yamanouchi Pharmaceutical Co., Ltd. Fused heteroaryl derivatives
US6403588B1 (en) 2000-04-27 2002-06-11 Yamanouchi Pharmaceutical Co., Ltd. Imidazopyridine derivatives
EP1353693B1 (fr) 2001-01-16 2005-03-16 Glaxo Group Limited Combinaison pharmaceutique contenant de l'amino-4 quinazoline et paclitaxel, carboplatin or vinorelbine pour le traitement du cancer
WO2002098863A1 (fr) * 2001-06-05 2002-12-12 Fujisawa Pharmaceutical Co., Ltd. Derive d'imidazole fondu
CA2454976C (fr) 2001-07-26 2011-05-10 Santen Pharmaceutical Co., Ltd. Agent therapeutique contre le glaucome contenant en tant qu'ingre dient actif un compose presentant un effet inhibiteur de la kinase pi3
US6703414B2 (en) 2001-09-14 2004-03-09 Arizona Board Of Regents On Behalf Of The University Of Arizona Device and method for treating restenosis
AU2002357667A1 (en) 2001-10-24 2003-05-06 Iconix Pharmaceuticals, Inc. Modulators of phosphoinositide 3-kinase
WO2003035618A2 (fr) 2001-10-24 2003-05-01 Iconix Pharmaceuticals, Inc. Modulateurs de la phosphoinositide 3-kinase
EP1444010A2 (fr) 2001-10-30 2004-08-11 Pharmacia Corporation Derives de carboxamide heteroaromatique destines au traitement des inflammations
BR0312650A (pt) 2002-07-10 2005-05-03 Applied Research Systems Derivados de benzeno fundido azolidinona-vinila
US20040092561A1 (en) 2002-11-07 2004-05-13 Thomas Ruckle Azolidinone-vinyl fused -benzene derivatives
WO2004006916A1 (fr) 2002-07-10 2004-01-22 Applied Research Systems Ars Holding Nv Utilisation de composes pour accroitre la motilite des spermatozoides
JP2005536518A (ja) * 2002-07-19 2005-12-02 ファルマシア コーポレイション 炎症治療のための置換チオフェンカルボキサミド化合物
WO2004017950A2 (fr) 2002-08-22 2004-03-04 Piramed Limited Inhibiteurs de phosphatidylinositol 3,5-biphosphate en tant qu'agents antiviraux
MXPA05008400A (es) * 2003-02-07 2005-10-05 Warner Lambert Co Derivados de oxazolidinona n-sustituidos por un anillo triciclico, para su uso como agentes antibacterianos.
EP1449844A1 (fr) * 2003-02-14 2004-08-25 Ferring B.V. derives de benzamide agonistes de l'ocytocine et antagonistes de la vasopressine
US20050239767A1 (en) * 2003-10-28 2005-10-27 Chan Michael K Intermolecular SNAr of the heterocycle-activated nitro and fluoro groups-application in the synthesis of polyazamacrocyclic ligands
CA2579279C (fr) * 2004-10-07 2013-10-01 Boehringer Ingelheim International Gmbh Derives de thiazole tricyclique en tant que pi3-kinases
GB0423653D0 (en) 2004-10-25 2004-11-24 Piramed Ltd Pharmaceutical compounds
EP1934174B1 (fr) 2005-10-07 2011-04-06 Exelixis, Inc. Azetidines en tant qu'inhibiteurs de mek et leur utilisation pour le traitement des maladies proliferatives
GB0520657D0 (en) 2005-10-11 2005-11-16 Ludwig Inst Cancer Res Pharmaceutical compounds
NZ572812A (en) 2006-04-26 2010-09-30 Hoffmann La Roche THIENO [3, 2-D] PYRIMIDINE Indazole DERIVATIVE USEFUL AS PI3K INHIBITOR
CL2007001166A1 (es) 2006-04-26 2008-01-25 Piramed Ltd Compuestos derivados de pirimidina condensada, inhibidores de pi3-quinasa; procesos para preparar los compuestos; composicion farmaceutica que los comprende; uso de los compuestos en la preparacion de medicamentos; proceso para preparar la composicion farmaceutica; y kit que incluye a la composicion farmaceutica
WO2008019139A2 (fr) 2006-08-04 2008-02-14 Beth Israel Deaconess Medical Center Inhibiteurs de la pyruvate kinase et procédés de traitement de maladie
US7649007B2 (en) 2006-08-15 2010-01-19 Wyeth Llc Oxazolidine derivatives as PR modulators
US8779154B2 (en) * 2006-09-26 2014-07-15 Qinglin Che Fused ring compounds for inflammation and immune-related uses
EP2114950B1 (fr) 2006-12-07 2016-03-09 Genentech, Inc. Composés inhibiteurs de la phosphoinositide 3-kinase et procédés d'utilisation
ES2544082T3 (es) 2006-12-07 2015-08-27 F. Hoffmann-La Roche Ag Compuestos inhibidores de fosfoinosítido 3-quinasa y métodos de uso
PL2276767T3 (pl) * 2008-03-31 2014-09-30 Genentech Inc Związki benzopiranowe i benzoksepinowe będące inhibitorami pi3k oraz metody ich stosowania
RS53164B (en) * 2009-09-28 2014-06-30 F. Hoffmann-La Roche Ag BENZOXAZEPINE PI3K INHIBITOR COMPOUNDS AND THEIR USE IN CANCER TREATMENT
SG10201407781SA (en) * 2009-09-28 2015-01-29 Hoffmann La Roche Benzoxepin PI3K Inhibitor Compounds And Methods Of Use

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CN104987345A (zh) 2015-10-21
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EP2483277B1 (fr) 2015-12-02
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