CA2778615C - Methods of synthesis and purification of heteroaryl compounds - Google Patents

Methods of synthesis and purification of heteroaryl compounds Download PDF

Info

Publication number
CA2778615C
CA2778615C CA2778615A CA2778615A CA2778615C CA 2778615 C CA2778615 C CA 2778615C CA 2778615 A CA2778615 A CA 2778615A CA 2778615 A CA2778615 A CA 2778615A CA 2778615 C CA2778615 C CA 2778615C
Authority
CA
Canada
Prior art keywords
pyrazin
dihydropyrazino
methyl
pyridin
triazol
Prior art date
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.)
Active
Application number
CA2778615A
Other languages
English (en)
French (fr)
Other versions
CA2778615A1 (en
Inventor
Roy L. Harris
John Sapienza
Graziella Shevlin
Patrick Papa
Branden Gingsee Lee
Garrick Packard
Jingjing Zhao
Patrick Anthony Jokiel
Deborah Mortensen
Jennifer Riggs
Juan Antonio Gamboa
Marie Georges Beauchamps
Matthew Michael Kreilein
Mohit Atul Kothare
Sophie Perrin-Ninkovic
Philip Pye
William Wei-Hwa Leong
Jan Elsner
Anusuya Choudhury
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Signal Pharmaceuticals LLC
Original Assignee
Signal Pharmaceuticals LLC
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
Application filed by Signal Pharmaceuticals LLC filed Critical Signal Pharmaceuticals LLC
Publication of CA2778615A1 publication Critical patent/CA2778615A1/en
Application granted granted Critical
Publication of CA2778615C publication Critical patent/CA2778615C/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • 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
    • A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • 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
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J23/00—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00
    • B01J23/16—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of arsenic, antimony, bismuth, vanadium, niobium, tantalum, polonium, chromium, molybdenum, tungsten, manganese, technetium or rhenium
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
    • C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
    • C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
    • C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members 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
    • C07D241/20—Nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
    • C07D498/14—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Immunology (AREA)
  • Obesity (AREA)
  • Materials Engineering (AREA)
  • Epidemiology (AREA)
  • Biomedical Technology (AREA)
  • Neurosurgery (AREA)
  • Emergency Medicine (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Neurology (AREA)
  • Endocrinology (AREA)
  • Cardiology (AREA)
  • Child & Adolescent Psychology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
  • Plural Heterocyclic Compounds (AREA)
CA2778615A 2009-10-26 2010-10-22 Methods of synthesis and purification of heteroaryl compounds Active CA2778615C (en)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US25491709P 2009-10-26 2009-10-26
US61/254,917 2009-10-26
US32848010P 2010-04-27 2010-04-27
US61/328,480 2010-04-27
PCT/US2010/053678 WO2011053518A1 (en) 2009-10-26 2010-10-22 Methods of synthesis and purification of heteroaryl compounds

Publications (2)

Publication Number Publication Date
CA2778615A1 CA2778615A1 (en) 2011-05-05
CA2778615C true CA2778615C (en) 2019-04-23

Family

ID=43922466

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2778615A Active CA2778615C (en) 2009-10-26 2010-10-22 Methods of synthesis and purification of heteroaryl compounds

Country Status (23)

Country Link
US (3) US8569494B2 (enExample)
EP (2) EP2493472B1 (enExample)
JP (2) JP2013508456A (enExample)
KR (2) KR101903925B1 (enExample)
CN (2) CN102686225A (enExample)
AR (1) AR078788A1 (enExample)
AU (1) AU2010313585B2 (enExample)
BR (1) BR112012009751A2 (enExample)
CA (1) CA2778615C (enExample)
CO (1) CO6541598A2 (enExample)
CR (1) CR20120211A (enExample)
EC (1) ECSP12011831A (enExample)
ES (2) ES2751705T3 (enExample)
IL (1) IL219368A (enExample)
MX (1) MX341704B (enExample)
MY (1) MY177695A (enExample)
NI (1) NI201200066A (enExample)
NZ (2) NZ618135A (enExample)
PH (2) PH12012500825A1 (enExample)
RU (1) RU2557242C2 (enExample)
SG (1) SG10201500511TA (enExample)
WO (1) WO2011053518A1 (enExample)
ZA (1) ZA201202959B (enExample)

Families Citing this family (61)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
PT2300013T (pt) 2008-05-21 2017-10-31 Ariad Pharma Inc Derivados de fósforo como inibidores de cinases
US9273077B2 (en) 2008-05-21 2016-03-01 Ariad Pharmaceuticals, Inc. Phosphorus derivatives as kinase inhibitors
US8110578B2 (en) * 2008-10-27 2012-02-07 Signal Pharmaceuticals, Llc Pyrazino[2,3-b]pyrazine mTOR kinase inhibitors for oncology indications and diseases associated with the mTOR/PI3K/Akt pathway
JP5590040B2 (ja) 2008-11-12 2014-09-17 アリアド・ファーマシューティカルズ・インコーポレイテッド キナーゼ阻害剤としてのピラジノピラジンおよび誘導体
EP2704572B1 (en) 2011-05-04 2015-12-30 Ariad Pharmaceuticals, Inc. Compounds for inhibiting cell proliferation in egfr-driven cancers
SG10201912850WA (en) * 2011-10-19 2020-02-27 Signal Pharm Llc Treatment Of Cancer With TOR Kinase Inhibitors
ES2694413T3 (es) * 2011-12-02 2018-12-20 Signal Pharmaceuticals, Llc Composiciones farmacéuticas de 7-(6-(2-hidroxipropan-2-il)piridin-3-il)-1-((trans)-4-metoxiciclohexil)-3,4-dihidropirazino [2,3-b]pirazin-2(1H)-ona, una forma sólida de la misma y métodos para su uso
AU2015201807B2 (en) * 2011-12-02 2016-12-08 Signal Pharmaceuticals, Llc Pharmaceutical compositions of 7-(6-(2-hydroxypropan-2-yl)pyridin-3-yl)-1-((trans)-4-methocyclohexyl)-3,4-dihydropyrazino[2,3-b] pyrazin-2(1H)-one, a solid form thereof and methods of their use
CA2864905A1 (en) 2012-02-24 2013-08-29 Signal Pharmaceuticals, Llc Methods for treating non- small cell lung cancer using tor kinase inhibitor combination therapy
MY178012A (en) 2012-03-15 2020-09-29 Signal Pharm Llc Treatment of cancer with tor kinase inhibitors
UA114194C2 (uk) 2012-03-15 2017-05-10 Сігнал Фармасьютікалз, Елелсі Лікування раку інгібітором тоr кінази
KR20200034818A (ko) 2012-03-15 2020-03-31 시그날 파마소티칼 엘엘씨 Tor 키나제 억제제를 사용한 암의 치료
ES2677874T3 (es) 2012-03-15 2018-08-07 Signal Pharmaceuticals, Llc Tratamiento del cáncer con inhibidores de la cinasa TOR
AU2013204563B2 (en) 2012-05-05 2016-05-19 Takeda Pharmaceutical Company Limited Compounds for inhibiting cell proliferation in EGFR-driven cancers
PE20190736A1 (es) 2012-06-13 2019-05-23 Incyte Holdings Corp Compuestos triciclicos sustituidos como inhibidores del receptor del factor de crecimiento de fibroblastos (fgfr)
AU2013203714B2 (en) 2012-10-18 2015-12-03 Signal Pharmaceuticals, Llc Inhibition of phosphorylation of PRAS40, GSK3-beta or P70S6K1 as a marker for TOR kinase inhibitory activity
AU2015213397B2 (en) * 2012-10-18 2017-07-27 Signal Pharmaceuticals, Llc Treatment of cancer with TOR kinase inhibitors
AU2013202768B2 (en) * 2012-10-18 2015-11-05 Signal Pharmaceuticals, Llc Treatment of cancer with TOR kinase inhibitors
EP2945636B1 (en) 2013-01-16 2017-06-28 Signal Pharmaceuticals, LLC Substituted pyrrolopyrimidine compounds, compositions thereof, and methods of treatment therewith
EP2961408A1 (en) * 2013-02-28 2016-01-06 Signal Pharmaceuticals, LLC Treatment of cancer with tor kinase inhibitors
US20140275502A1 (en) * 2013-03-13 2014-09-18 Dow Agrosciences Llc Process for the preparation of certain triaryl rhamnose carbamates
US9273399B2 (en) 2013-03-15 2016-03-01 Ppg Industries Ohio, Inc. Pretreatment compositions and methods for coating a battery electrode
US9611283B1 (en) 2013-04-10 2017-04-04 Ariad Pharmaceuticals, Inc. Methods for inhibiting cell proliferation in ALK-driven cancers
NZ629411A (en) 2013-04-17 2017-06-30 Signal Pharm Llc Treatment of cancer with dihydropyrazino-pyrazines
ES2944478T3 (es) * 2013-04-17 2023-06-21 Signal Pharm Llc 1-etil-7-(2-metil-6-(1H-1,2,4-triazol-3-il)piridin-3-il)-3,4-dihidropirazino[2,3-b]pirazin-2(1H)-ona para tratar el glioblastoma multiforme
SG11201508527VA (en) * 2013-04-17 2015-11-27 Signal Pharm Llc Pharmaceutical formulations, processes, solid forms and methods of use relating to 1-ethyl-7-(2-methyl-6-(1h-1,2,4-triazol-3-yl) pyridin-3-yl) -3,4-dihydropyrazino[2,3-b]pyrazin-2(1h)-one
JP2016522177A (ja) * 2013-04-17 2016-07-28 シグナル ファーマシューティカルズ，エルエルシー ジヒドロピラジノ−ピラジンによる癌治療
AU2014254057A1 (en) 2013-04-17 2015-11-05 Signal Pharmaceuticals, Llc Combination therapy comprising a TOR kinase inhibitor and N-(3-(5-fluoro-2-(4-(2-methoxyethoxy)phenylamino)pyrimidin-4-ylamino)phenyl)acrylamide for treating cancer
MX368286B (es) * 2013-04-17 2019-09-27 Signal Pharm Llc Terapia de combinacion que comprende un inhibidor de tor cinasa y un compuesto de quinazolinona 5-sustituida para tratar cancer.
KR102242505B1 (ko) * 2013-04-17 2021-04-20 시그날 파마소티칼 엘엘씨 암 치료용 tor 키나제 억제제 및 시티딘 유사체를 포함하는 병용 요법
TW201526897A (zh) * 2013-04-17 2015-07-16 Signal Pharm Llc 使用ｔｏｒ激酶抑制劑組合療法以治療癌症之方法
BR112015026257B1 (pt) * 2013-04-17 2022-12-20 Signal Pharmaceuticals, Llc Uso de um composto dihidropirazino-pirazina e enzalutamida, composição farmacêutica que os compreende, e kit
KR102269032B1 (ko) 2013-04-19 2021-06-24 인사이트 홀딩스 코포레이션 Fgfr 저해제로서 이환식 헤테로사이클
JP6401250B2 (ja) * 2013-05-29 2018-10-10 シグナル ファーマシューティカルズ，エルエルシー ７−（６−（２−ヒドロキシプロパン−２−イル）ピリジン−３−イル）−１−（（ｔｒａｎｓ）−４−メトキシシクロヘキシル）−３，４−ジヒドロピラジノ［２，３−ｂ］ピラジン−２（１Ｈ）−オン、その固体形態の医薬組成物、及びその使用方法
MX2016004212A (es) 2013-10-04 2016-07-11 Signal Pharm Llc Inhibidor de tor cinasa en la prevencion o tratamiento de cancer caracterizado por mutaciones genicas.
US9512129B2 (en) 2014-04-16 2016-12-06 Signal Pharmaceuticals, Llc Solid forms comprising 1-ethyl-7-(2-methyl-6-(1H-1,2,4-triazol-3-yl)pyridin-3-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one and a coformer
NZ714742A (en) * 2014-04-16 2017-04-28 Signal Pharm Llc Solid forms of 1-ethyl-7-(2-methyl-6-(1h-1,2,4-triazol-3-yl)pyridin-3-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1h)-one, compositions thereof and methods of their use
US9718824B2 (en) 2014-04-16 2017-08-01 Signal Pharmaceuticals, Llc Solid forms comprising 7-(6-(2-hydroxypropan-2-yl)pyridin-3-yl)-1-((trans)-4-methoxycyclohexyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one, and a coformer, compositions and methods of use thereof
US9737535B2 (en) 2014-04-16 2017-08-22 Signal Pharmaceuticals, Llc Methods for treating cancer using TOR kinase inhibitor combination therapy comprising administering substituted pyrazino[2,3-b]pyrazines
AU2015289929A1 (en) 2014-07-14 2017-03-02 Signal Pharmaceuticals, Llc Methods of treating a cancer using substituted pyrrolopyrimidine compounds, compositions thereof
NZ629796A (en) 2014-07-14 2015-12-24 Signal Pharm Llc Amorphous form of 4-((4-(cyclopentyloxy)-5-(2-methylbenzo[d]oxazol-6-yl)-7h-pyrrolo[2,3-d]pyrimidin-2-yl)amino)-3-methoxy-n-methylbenzamide, compositions thereof and methods of their use
US10851105B2 (en) 2014-10-22 2020-12-01 Incyte Corporation Bicyclic heterocycles as FGFR4 inhibitors
MA41551A (fr) 2015-02-20 2017-12-26 Incyte Corp Hétérocycles bicycliques utilisés en tant qu'inhibiteurs de fgfr4
ES2895769T3 (es) 2015-02-20 2022-02-22 Incyte Corp Heterociclos bicíclicos como inhibidores de FGFR
AR111960A1 (es) 2017-05-26 2019-09-04 Incyte Corp Formas cristalinas de un inhibidor de fgfr y procesos para su preparación
EP3641772B1 (en) 2017-06-22 2023-08-02 Celgene Corporation Treatment of hepatocellular carcinoma characterized by hepatitis b virus infection
SG11202010882XA (en) 2018-05-04 2020-11-27 Incyte Corp Salts of an fgfr inhibitor
SI3788047T1 (sl) 2018-05-04 2024-11-29 Incyte Corporation Trdne oblike inhibitorja fgfr in postopki priprave le-teh
WO2020185532A1 (en) 2019-03-08 2020-09-17 Incyte Corporation Methods of treating cancer with an fgfr inhibitor
US11591329B2 (en) 2019-07-09 2023-02-28 Incyte Corporation Bicyclic heterocycles as FGFR inhibitors
WO2021067374A1 (en) 2019-10-01 2021-04-08 Incyte Corporation Bicyclic heterocycles as fgfr inhibitors
US11607416B2 (en) 2019-10-14 2023-03-21 Incyte Corporation Bicyclic heterocycles as FGFR inhibitors
US11566028B2 (en) 2019-10-16 2023-01-31 Incyte Corporation Bicyclic heterocycles as FGFR inhibitors
WO2021113462A1 (en) 2019-12-04 2021-06-10 Incyte Corporation Derivatives of an fgfr inhibitor
EP4069696A1 (en) 2019-12-04 2022-10-12 Incyte Corporation Tricyclic heterocycles as fgfr inhibitors
WO2021146424A1 (en) 2020-01-15 2021-07-22 Incyte Corporation Bicyclic heterocycles as fgfr inhibitors
WO2021219090A1 (zh) * 2020-04-29 2021-11-04 北京泰德制药股份有限公司 喹喔啉二酮衍生物作为kras g12c突变蛋白的不可逆抑制剂
WO2022166866A1 (zh) * 2021-02-08 2022-08-11 南京明德新药研发有限公司 二氢吡嗪并吡嗪类大环化合物
WO2022221170A1 (en) 2021-04-12 2022-10-20 Incyte Corporation Combination therapy comprising an fgfr inhibitor and a nectin-4 targeting agent
WO2022261159A1 (en) 2021-06-09 2022-12-15 Incyte Corporation Tricyclic heterocycles as fgfr inhibitors
WO2022261160A1 (en) 2021-06-09 2022-12-15 Incyte Corporation Tricyclic heterocycles as fgfr inhibitors

Family Cites Families (67)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3507866A (en) 1967-08-08 1970-04-21 Merck & Co Inc 1h - imidazo(4,5-b)pyrazin - 2 - one and processes for their preparation
US3567725A (en) 1968-11-20 1971-03-02 Merck & Co Inc Process for preparation of 1h-imidazo-(4,5-b)pyrazin-2-ones
US4294837A (en) 1980-03-28 1981-10-13 Sterling Drug Inc. 1,3-Dihydro-6-(pyridinyl)-2H-imidazo[4,5-b]pyridin-2-ones and -imidazo[4,5-b]pyridine-2-thiones and their cardiotonic use
US4317909A (en) 1980-03-24 1982-03-02 Sterling Drug Inc. Preparation of 1,3-dihydro-5-(pyridinyl)-2H-imidazo[4,5-b]pyridin-2-ones
US4294836A (en) 1980-03-24 1981-10-13 Sterling Drug Inc. 1,3-Dihydro-6-(pyridinyl)-2H-imidazo[4,5-b]pyridin-2-ones and -imidazo[4,5-b]-pyridine-2-thiones and their cardiotonic use
US4309537A (en) 1980-03-28 1982-01-05 Sterling Drug Inc. Production of imidazo[4,5-b]pyridin-2-ones or thiones
GB8709448D0 (en) 1987-04-21 1987-05-28 Pfizer Ltd Heterobicyclic quinoline derivatives
JPS63275582A (ja) 1987-05-02 1988-11-14 Naade Kenkyusho:Kk ２−アミノイミダゾ〔４，５−ｂ〕ピリジン誘導体の製造方法
DD262026A1 (de) 1987-07-10 1988-11-16 Akad Wissenschaften Ddr Verfahren zur herstellung von 4-substituierten 6-(pyrid-4-yl)-2,4-dihydro-1h-imidazo[4,5-b]pyrid-2-onen
FR2643903A1 (fr) 1989-03-03 1990-09-07 Union Pharma Scient Appl Nouveaux derives de benzimidazole, leurs procedes de preparation, intermediaires de synthese, compositions pharmaceutiques les contenant, utiles notamment pour le traitement des maladies cardiovasculaires, et des ulceres duodenaux
US4963561A (en) 1990-02-28 1990-10-16 Sterling Drug Inc. Imidazopyridines, their preparation and use
TW274550B (enExample) * 1992-09-26 1996-04-21 Hoechst Ag
US6015774A (en) * 1995-09-22 2000-01-18 Sumitomo Chemical Company, Limited Pyrazin-2-one derivatives, their use, and intermediates for their production
DE19601627A1 (de) 1996-01-18 1997-07-24 Bayer Ag Heteroatomhaltige Cyclopentanopyridyl-Oxazolidinone
US6031105A (en) * 1996-04-09 2000-02-29 Pfizer Inc Substituted pyridines
ES2230719T3 (es) 1997-09-26 2005-05-01 Zentaris Gmbh Compuestos basados en azabencimidazol para modular una funcion de proteina-quinasa de serina/treonina.
ZA9810490B (en) 1997-12-03 1999-05-20 Dainippon Pharmaceutical Co 2-Aryl-8-oxodihydropurine derivative process for the preparation thereof pharmaceutical composition containing the same and intermediate therefor
JP2003146987A (ja) 1999-05-31 2003-05-21 Dainippon Pharmaceut Co Ltd ２−アリールプリン−９−アセトアミド誘導体
JP3814125B2 (ja) 1999-06-02 2006-08-23 大日本住友製薬株式会社 ２−アリール−８−オキソジヒドロプリン誘導体からなる医薬
JP2002100363A (ja) 2000-09-25 2002-04-05 Mitsubishi Chemicals Corp リチウム二次電池用正極材料、リチウム二次電池用正極及びリチウム二次電池
JP2002167387A (ja) 2000-11-29 2002-06-11 Dainippon Pharmaceut Co Ltd ２−（７，８−ジヒドロ−８−オキソ−９ｈ−プリン−９−イル）酢酸誘導体
MXPA03004245A (es) 2000-12-12 2003-09-22 Neurogen Corp Espiro[isobenzofuran-1,4'piperidin]-3-onas y 3h-espiroisobenzofuran-1,4'-piperidinas.
WO2002076954A1 (en) 2001-03-23 2002-10-03 Smithkline Beecham Corporation Compounds useful as kinase inhibitors for the treatment of hyperproliferative diseases
HRP20040213A2 (en) 2001-09-04 2005-02-28 Boehringer Ingelheim Pharma Gmbh & Co.Kg Novel dihydropteridinones, method for producing the same and the use thereof as medicaments
JP2005506350A (ja) 2001-10-18 2005-03-03 ベーリンガー インゲルハイム ファーマシューティカルズ インコーポレイテッド サイトカイン阻害薬としての１，４−二置換ベンゾ−縮合尿素化合物
US7247621B2 (en) 2002-04-30 2007-07-24 Valeant Research & Development Antiviral phosphonate compounds and methods therefor
AU2003232071A1 (en) 2002-05-06 2003-11-17 Genelabs Technologies, Inc. Nucleoside derivatives for treating hepatitis c virus infection
US20040204420A1 (en) 2002-08-05 2004-10-14 Rana Tariq M. Compounds for modulating RNA interference
US7199119B2 (en) 2002-10-31 2007-04-03 Amgen Inc. Antiinflammation agents
RU2005118401A (ru) * 2002-11-12 2006-01-10 Байер Фармасьютикалс Корпорейшн (US) Производные индолилпиразинона, применимые для лечения гиперпролиферативных нарушений и заболеваний, связанных с ангиогенезом
WO2004065378A1 (en) 2003-01-17 2004-08-05 Warner-Lambert Company Llc 2-aminopyridine substituted heterocycles as inhibitors of cellular proliferation
KR100983462B1 (ko) 2003-02-26 2010-09-27 베링거 잉겔하임 파르마 게엠베하 운트 코 카게 디하이드로프테리디논, 이의 제조방법 및 약제로서의 이의 용도
GB2400101A (en) 2003-03-28 2004-10-06 Biofocus Discovery Ltd Compounds capable of binding to the active site of protein kinases
EP4032897B1 (en) 2003-05-30 2025-01-29 Gilead Pharmasset LLC Modified fluorinated nucleoside analogues
US7476665B2 (en) 2003-06-26 2009-01-13 Merck & Co., Inc. Benzodiazepine CGRP receptor antagonists
CA2569406A1 (en) 2004-06-04 2005-12-22 Icos Corporation Methods for treating mast cell disorders
DE102004029784A1 (de) 2004-06-21 2006-01-05 Boehringer Ingelheim Pharma Gmbh & Co. Kg Neue 2-Benzylaminodihydropteridinone, Verfahren zur deren Herstellung und deren Verwendung als Arzneimittel
WO2006001266A1 (ja) 2004-06-23 2006-01-05 Banyu Pharmaceutical Co., Ltd. ２－アリールプリン誘導体の製造方法
GB0420719D0 (en) 2004-09-17 2004-10-20 Addex Pharmaceuticals Sa Novel allosteric modulators
US7608622B2 (en) 2004-09-24 2009-10-27 Janssen Pharmaceutica Nv Imidazo[4,5-b]pyrazinone inhibitors of protein kinases
CA2577588C (en) 2004-10-29 2013-09-10 Tibotec Pharmaceuticals Ltd. Hiv inhibiting bicyclic pyrimidine derivatives
WO2006050076A1 (en) 2004-10-29 2006-05-11 Janssen Pharmaceutica, N.V. Pyrimidinyl substituted fused-pyrrolyl compounds useful in treating kinase disorders
SE0403006D0 (sv) * 2004-12-09 2004-12-09 Biovitrum Ab New compounds
EP1828186A1 (en) 2004-12-13 2007-09-05 Sunesis Pharmaceuticals, Inc. Pyrido pyrimidinones, dihydro pyrimido pyrimidinones and pteridinones useful as raf kinase inhibitors
ES2308731T3 (es) 2005-02-16 2008-12-01 Astrazeneca Ab Compuestos quimicos.
WO2006091737A1 (en) 2005-02-24 2006-08-31 Kemia, Inc. Modulators of gsk-3 activity
EP1869049B1 (en) * 2005-03-21 2009-03-04 Eli Lilly And Company Imidazopyridazine compounds
AU2006232105A1 (en) 2005-04-05 2006-10-12 Pharmacopeia, Inc. Purine and imidazopyridine derivatives for immunosuppression
GB0519245D0 (en) * 2005-09-20 2005-10-26 Vernalis R&D Ltd Purine compounds
JP2009523701A (ja) * 2005-12-28 2009-06-25 武田薬品工業株式会社 縮合複素環化合物およびその用途
WO2007079186A2 (en) * 2005-12-30 2007-07-12 Merck & Co., Inc. 1, 3-oxazolidin-2-one derivatives useful as cetp inhibitors
US20090281075A1 (en) 2006-02-17 2009-11-12 Pharmacopeia, Inc. Isomeric purinones and 1h-imidazopyridinones as pkc-theta inhibitors
SI2013208T1 (sl) * 2006-04-21 2011-09-30 Pfizer Prod Inc Piridin(3,4-b)pirazinoni
DK2069352T5 (en) 2006-08-02 2017-04-03 Cytokinetics Inc SPECIFIC CHEMICAL UNITS, COMPOSITIONS AND PROCEDURES
US8268809B2 (en) 2006-09-05 2012-09-18 Emory University Kinase inhibitors for preventing or treating pathogen infection and method of use thereof
WO2008030744A2 (en) 2006-09-05 2008-03-13 Board Of Regents, The University Of Texas System Inhibitors of c-met and uses thereof
AR063142A1 (es) 2006-10-04 2008-12-30 Pharmacopeia Inc Derivados de 2-(bencimidazolil) purina y purinonas 6-sustituidas utiles como inmunosupresores,y composiciones farmaceuticas que los contienen.
US7902187B2 (en) 2006-10-04 2011-03-08 Wyeth Llc 6-substituted 2-(benzimidazolyl)purine and purinone derivatives for immunosuppression
EP2457913B1 (en) * 2006-10-19 2017-04-19 Signal Pharmaceuticals, LLC Heteroaryl compounds, compositions thereof, and methods of treatment therewith
ES2383370T3 (es) 2006-10-19 2012-06-20 Signal Pharmaceuticals Llc Compuestos de heteroarilo, sus composiciones y uso de los mismos como inhibidores de proteína quinasa
SA08290245B1 (ar) * 2007-04-23 2012-02-12 استرازينيكا ايه بي مشتقات كربو كساميد جديدة من -n (8-اريل رباعي هيدرو نفثالين غير متجانس- 2- يل) أو -n (5-اريل كرومان غير متجانس -3-يل) لعلاج الألم
AR067027A1 (es) * 2007-06-19 2009-09-30 Astrazeneca Ab Derivados de 2, 3-dihidro-1h-pirrol[3, 4b]quinolin-1-ona, una composicion farmaceutica que los comprende y su uso en la fabricacion de un medicamento para el tratamiento de enfermedades mediadas por la modulacion de la actividad del receptor gaba a.
JP2009046435A (ja) * 2007-08-21 2009-03-05 Mitsubishi Tanabe Pharma Corp グルココルチコイド受容体モジュレーター
US8067459B2 (en) * 2007-10-16 2011-11-29 Arqule, Inc. Lapachone compounds and methods of use thereof
CA2709784A1 (en) 2007-12-21 2009-07-09 University Of Rochester Method for altering the lifespan of eukaryotic organisms
US8110578B2 (en) * 2008-10-27 2012-02-07 Signal Pharmaceuticals, Llc Pyrazino[2,3-b]pyrazine mTOR kinase inhibitors for oncology indications and diseases associated with the mTOR/PI3K/Akt pathway
EP2379561B1 (en) 2008-11-25 2015-11-04 University Of Rochester Mlk inhibitors and methods of use

Also Published As

Publication number Publication date
ES2613664T3 (es) 2017-05-25
IL219368A0 (en) 2012-06-28
ECSP12011831A (es) 2012-06-29
US8686135B2 (en) 2014-04-01
ES2751705T3 (es) 2020-04-01
NI201200066A (es) 2012-08-13
US20130245254A1 (en) 2013-09-19
EP3091021B1 (en) 2019-08-28
RU2012121806A (ru) 2013-12-10
EP3091021A1 (en) 2016-11-09
EP2493472B1 (en) 2016-12-07
MY177695A (en) 2020-09-23
WO2011053518A1 (en) 2011-05-05
AU2010313585A1 (en) 2012-05-17
EP2493472A1 (en) 2012-09-05
BR112012009751A2 (pt) 2020-09-24
PH12014500392A1 (en) 2015-06-01
CN102686225A (zh) 2012-09-19
ZA201202959B (en) 2013-06-26
NZ599549A (en) 2013-11-29
MX341704B (es) 2016-08-31
CN106117213A (zh) 2016-11-16
MX2012004887A (es) 2012-06-08
AR078788A1 (es) 2011-11-30
EP2493472A4 (en) 2013-03-13
US20140155593A1 (en) 2014-06-05
IL219368A (en) 2016-10-31
PH12012500825A1 (en) 2015-03-13
US20110137028A1 (en) 2011-06-09
CN106117213B (zh) 2022-03-18
US8569494B2 (en) 2013-10-29
US9079900B2 (en) 2015-07-14
RU2557242C2 (ru) 2015-07-20
JP2017014240A (ja) 2017-01-19
CA2778615A1 (en) 2011-05-05
JP2013508456A (ja) 2013-03-07
CO6541598A2 (es) 2012-10-16
PH12014500392B1 (en) 2015-06-01
KR20170120196A (ko) 2017-10-30
SG10201500511TA (en) 2015-03-30
KR101903925B1 (ko) 2018-10-02
JP6338622B2 (ja) 2018-06-06
AU2010313585B2 (en) 2015-11-26
NZ618135A (en) 2015-05-29
CR20120211A (es) 2012-07-30
KR20120091240A (ko) 2012-08-17

Similar Documents

Publication Publication Date Title
CA2778615C (en) Methods of synthesis and purification of heteroaryl compounds
JP5766820B2 (ja) Ｐｉ３キナーゼ阻害剤としての複素環化合物
CA3084090A1 (en) Novel compounds and pharmaceutical compositions thereof for the treatment of diseases
EP2539337A1 (en) Pyrido[3,2-d]pyrimidine pi3k delta inhibitor compounds and methods of use
WO2016050921A1 (en) Pyrazole carboxamide compounds for use in the treament of disorders mediated by bruton's tyrosine kinase (btk)
AU2013270326A1 (en) Pyrrolo[2,1-f][1,2,4]triazine compound, and preparation method and application thereof
MX2013000389A (es) Compuestos de purina selectivos para fosfatidilinositol 3-cinasa p110 delta, y metodods de uso.
KR20130029756A (ko) Ｎ-7 치환된 퓨린 및 피라졸로피리미딘 화합물, 조성물 및 사용 방법
AU2021373162A1 (en) Pyrazolopyridazinone compound, and pharmaceutical composition and use thereof
KR20140015157A (ko) Ａｋｔ 활성 억제제
UA110694C2 (uk) Способи одержання і очищення гетероарильних сполук
HK1177743A (en) Pyrido[3,2-d]pyrimidine pi3k delta inhibitor compounds and methods of use
NZ624021B2 (en) Heteroaryl pyridone and aza-pyridone compounds as inhibitors of btk activity
NZ624021A (en) Heteroaryl pyridone and aza-pyridone compounds as inhibitors of btk activity

Legal Events

Date Code Title Description
EEER Examination request

Effective date: 20150922