CN104918940B - 人磷脂酰肌醇3‑激酶δ的嘌呤抑制剂 - Google Patents

人磷脂酰肌醇3‑激酶δ的嘌呤抑制剂 Download PDF

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Publication number
CN104918940B
CN104918940B CN201380070631.4A CN201380070631A CN104918940B CN 104918940 B CN104918940 B CN 104918940B CN 201380070631 A CN201380070631 A CN 201380070631A CN 104918940 B CN104918940 B CN 104918940B
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China
Prior art keywords
ethyl
purin
pyrrolidin
amino
methylpyrimidin
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Expired - Fee Related
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CN201380070631.4A
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Chinese (zh)
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CN104918940A (zh
Inventor
A.A.阿查布
M.D.阿尔特曼
Y.邓
S.卡塔
J.D.卡茨
J.L.梅索特
H.周
M.麦克戈万
M.P.克里斯托弗
Y.加西亚
N.J.安东尼
F.X.弗拉德拉利纳斯
L.杨
C.穆
X.王
F.施
B.叶
S.张
X.赵
R.张
K.C.冯
X.冷
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Merck Sharp and Dohme LLC
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Merck Sharp and Dohme LLC
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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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D473/00—Heterocyclic compounds containing purine ring systems
    • C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
    • C07D473/32—Nitrogen atom
    • C07D473/34—Nitrogen atom attached in position 6, e.g. adenine
    • 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
    • A61K31/52—Purines, e.g. adenine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
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    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • 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
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • A—HUMAN NECESSITIES
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    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
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    • A61P37/08—Antiallergic agents
    • A—HUMAN NECESSITIES
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    • 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
    • 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

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  • Health & Medical Sciences (AREA)
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  • Veterinary Medicine (AREA)
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  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
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  • Engineering & Computer Science (AREA)
  • Immunology (AREA)
  • Pulmonology (AREA)
  • Rheumatology (AREA)
  • Transplantation (AREA)
  • Pain & Pain Management (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Dermatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
CN201380070631.4A 2012-11-16 2013-11-15 人磷脂酰肌醇3‑激酶δ的嘌呤抑制剂 Expired - Fee Related CN104918940B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201261727392P 2012-11-16 2012-11-16
US61/727,392 2012-11-16
PCT/CN2013/001395 WO2014075393A1 (en) 2012-11-16 2013-11-15 Purine inhibitors of human phosphatidylinositol 3-kinase delta

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CN104918940A CN104918940A (zh) 2015-09-16
CN104918940B true CN104918940B (zh) 2017-03-08

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US (1) US9938281B2 (enExample)
EP (1) EP2920172B1 (enExample)
JP (1) JP6322200B2 (enExample)
KR (1) KR20150084992A (enExample)
CN (1) CN104918940B (enExample)
AU (1) AU2013347539B2 (enExample)
BR (1) BR112015011147A8 (enExample)
CA (1) CA2891013A1 (enExample)
MX (1) MX2015006192A (enExample)
RU (1) RU2661896C2 (enExample)
WO (1) WO2014075393A1 (enExample)

Families Citing this family (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8193182B2 (en) 2008-01-04 2012-06-05 Intellikine, Inc. Substituted isoquinolin-1(2H)-ones, and methods of use thereof
MX358640B (es) 2008-01-04 2018-08-29 Intellikine Llc Isoquinolin-1 (2h) -onas y tieno [2,3-d]pirimidin-4(3h) -onas substituidas, y metodos de uso de las mismas.
TWI546305B (zh) 2011-01-10 2016-08-21 英菲尼提製藥股份有限公司 製備異喹啉酮之方法及異喹啉酮之固體形式
US8828998B2 (en) 2012-06-25 2014-09-09 Infinity Pharmaceuticals, Inc. Treatment of lupus, fibrotic conditions, and inflammatory myopathies and other disorders using PI3 kinase inhibitors
CN105102000B (zh) 2012-11-01 2021-10-22 无限药品公司 使用pi3激酶亚型调节剂的癌症疗法
WO2015160975A2 (en) 2014-04-16 2015-10-22 Infinity Pharmaceuticals, Inc. Combination therapies
WO2015178955A1 (en) * 2014-05-19 2015-11-26 Eternity Bioscience Inc. Substituted ethynyl heterobicyclic compounds as tyrosine kinase inhibitors
WO2015188369A1 (en) * 2014-06-13 2015-12-17 Merck Sharp & Dohme Corp. Purine inhibitors of human phosphatidylinositol 3-kinase delta
KR101710127B1 (ko) 2014-08-29 2017-02-27 한화제약주식회사 야누스인산화효소 억제제로서의 치환된 N-(피롤리딘-3-일)-7H-피롤로[2,3-d]피리미딘-4-아민
WO2017000125A1 (en) 2015-06-29 2017-01-05 Merck Sharp & Dohme Corp. Purine inhibitors of human phosphatidylinositol 3-kinase delta
WO2017166104A1 (en) * 2016-03-30 2017-10-05 Merck Sharp & Dohme Corp. Purine inhibitors of human phosphatidylinositol 3-kinase delta
EP3474856B1 (en) 2016-06-24 2022-09-14 Infinity Pharmaceuticals, Inc. Combination therapies
IL266109B2 (en) * 2016-10-21 2025-05-01 Nimbus Lakshmi Inc Tyk2 inhibitors and uses thereof
CN108892635A (zh) * 2018-09-07 2018-11-27 江苏工程职业技术学院 一种西沙必利关键中间体的制备方法
CN114269383A (zh) * 2019-01-08 2022-04-01 菲斯生物制药公司 金属酶抑制剂化合物
PH12022551379A1 (en) 2019-12-06 2023-05-03 Vertex Pharma Substituted tetrahydrofurans as modulators of sodium channels
DK4347031T3 (da) 2021-06-04 2025-12-01 Vertex Pharma N-(hydroxyalkyl-(hetero)aryl)-tetrahydrofuran-carboxamider som modulatorer af natriumkanaler
WO2024083237A1 (en) * 2022-10-20 2024-04-25 Impact Therapeutics (Shanghai) , Inc Substituted heteroaryl bicyclic compounds as usp1 inhibitors and the use thereof
IL321433A (en) 2022-12-16 2025-08-01 Astrazeneca Ab Purines 2,6,9 trimethylated

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101031569A (zh) * 2004-05-13 2007-09-05 艾科斯有限公司 作为人磷脂酰肌醇3－激酶δ抑制剂的喹唑啉酮
WO2011075630A1 (en) * 2009-12-18 2011-06-23 Incyte Corporation Substituted fused aryl and heteroaryl derivatives as pi3k inhibitors
CN102838600A (zh) * 2011-06-24 2012-12-26 山东亨利医药科技有限责任公司 苯基喹唑啉类PI3Kδ抑制剂

Family Cites Families (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4166452A (en) 1976-05-03 1979-09-04 Generales Constantine D J Jr Apparatus for testing human responses to stimuli
US4256108A (en) 1977-04-07 1981-03-17 Alza Corporation Microporous-semipermeable laminated osmotic system
US4265874A (en) 1980-04-25 1981-05-05 Alza Corporation Method of delivering drug with aid of effervescent activity generated in environment of use
US5117830A (en) 1990-11-08 1992-06-02 Whitby Research, Inc. Method of determining viability of tissue
US5877179A (en) * 1992-09-29 1999-03-02 The United States Of America As Represented By The Department Of Health And Human Services Xanthines for identifying CFTR--binding compounds useful for activating chloride conductance in animal cells
RU2112765C1 (ru) * 1993-02-09 1998-06-10 Дзе Велкам Фаундейшн Лимитед ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ, ПРОЯВЛЯЮЩАЯ АКТИВНОСТЬ ПРОТИВ ВИРУСНОЙ ИНФЕКЦИИ И β D-АРАБИНОФУРАНОЗИЛ-2-АМИНО-6-МЕТОКСИ-9Н-ПУРИНЫ
US5670501A (en) * 1994-09-01 1997-09-23 Discovery Therapeutics, Inc. N-substituted 9-alkyladenines
EE200100502A (et) * 1999-03-26 2002-12-16 Astrazeneca Ab Ühendid
WO2004112793A1 (en) 2003-05-23 2004-12-29 Chiron Corporation Guanidino-substituted quinazolinone compounds as mc4-r agonists
EP1751159A2 (en) * 2004-04-28 2007-02-14 Cv Therapeutics, Inc. Purine derivatives as a1 adenosine receptor antagonists
JP4820290B2 (ja) 2004-05-13 2011-11-24 第一三共株式会社 置換ピロリジン誘導体
WO2006099204A1 (en) 2005-03-11 2006-09-21 Aderis Pharmaceuticals, Inc. Substituted 9-alkyladenines and the use thereof
JO2660B1 (en) 2006-01-20 2012-06-17 نوفارتيس ايه جي Pi-3 inhibitors and methods of use
US7795427B2 (en) * 2006-02-14 2010-09-14 New York University Methods for inhibiting osteoclast differentiation, formation, or function and for increasing bone mass
US8759359B2 (en) * 2009-12-18 2014-06-24 Incyte Corporation Substituted heteroaryl fused derivatives as PI3K inhibitors
DE102010011431A1 (de) * 2009-12-23 2011-06-30 WABCO GmbH, 30453 Ventileinrichtung für eine Luftfederungsanlage
NZ627520A (en) 2010-03-10 2015-10-30 Astrazeneca Ab 4-phenyl pyridine analogues as protein kinase inhibitors
CN102869359A (zh) 2010-03-17 2013-01-09 弗·哈夫曼-拉罗切有限公司 咪唑并吡啶和嘌呤化合物、组合物和使用方法
MX2012015143A (es) * 2010-06-30 2013-07-03 Amgen Inc Compuestos heterociclicos que contienen nitrogeno como inhibidores de pi3k delta.
UA112517C2 (uk) * 2010-07-06 2016-09-26 Новартіс Аг Тетрагідропіридопіримідинові похідні
ES2612503T3 (es) * 2010-09-14 2017-05-17 Exelixis, Inc. Compuestos 9H-purina como inhibidores de PI3K-delta y métodos para su preparación
EP2632898A4 (en) * 2010-10-29 2014-04-02 Biogen Idec Inc HETEROCYCLIC TYROSINE KINASE HEMMER
EP2518070A1 (en) * 2011-04-29 2012-10-31 Almirall, S.A. Pyrrolotriazinone derivatives as PI3K inhibitors

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101031569A (zh) * 2004-05-13 2007-09-05 艾科斯有限公司 作为人磷脂酰肌醇3－激酶δ抑制剂的喹唑啉酮
WO2011075630A1 (en) * 2009-12-18 2011-06-23 Incyte Corporation Substituted fused aryl and heteroaryl derivatives as pi3k inhibitors
CN102838600A (zh) * 2011-06-24 2012-12-26 山东亨利医药科技有限责任公司 苯基喹唑啉类PI3Kδ抑制剂

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BR112015011147A2 (pt) 2017-07-11
RU2661896C2 (ru) 2018-07-23
CA2891013A1 (en) 2014-05-22
BR112015011147A8 (pt) 2019-10-01
EP2920172A4 (en) 2016-05-25
KR20150084992A (ko) 2015-07-22
AU2013347539B2 (en) 2017-06-15
EP2920172A1 (en) 2015-09-23
EP2920172B1 (en) 2019-12-25
JP6322200B2 (ja) 2018-05-09
RU2015122894A (ru) 2017-01-10
US20160207926A1 (en) 2016-07-21
CN104918940A (zh) 2015-09-16
MX2015006192A (es) 2015-08-10
AU2013347539A1 (en) 2015-05-07
US9938281B2 (en) 2018-04-10
JP2016502522A (ja) 2016-01-28
WO2014075393A1 (en) 2014-05-22

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