CN105503862B - 流感病毒复制抑制剂 - Google Patents

流感病毒复制抑制剂 Download PDF

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Publication number
CN105503862B
CN105503862B CN201510893703.6A CN201510893703A CN105503862B CN 105503862 B CN105503862 B CN 105503862B CN 201510893703 A CN201510893703 A CN 201510893703A CN 105503862 B CN105503862 B CN 105503862B
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China
Prior art keywords
compound
fluoro
independently
minutes
pyrrolo
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Expired - Fee Related
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CN201510893703.6A
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Chinese (zh)
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CN105503862A (zh
Inventor
P·S·查理弗森
M·P·克拉克
U·K·班达拉格
R·S·贝希尔
M·J·博伊德
I·戴维斯
邓红波
J·P·杜菲
L·J·弗雷姆尔
高淮
顾文鑫
J·M·肯尼迪
B·莱德弗德
M·W·里德博尔
F·玛尔泰斯
E·佩罗拉
王天生
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Vertex Pharmaceuticals Inc
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Vertex Pharmaceuticals Inc
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    • 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
    • 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
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • 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
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/351—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom not condensed with another ring
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/4353—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
    • A61K31/437—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 containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—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
    • A61K31/4965—Non-condensed pyrazines
    • A61K31/497—Non-condensed pyrazines containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—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
    • 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
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • 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)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Virology (AREA)
  • Molecular Biology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Biochemistry (AREA)
  • Emergency Medicine (AREA)
  • Pulmonology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
CN201510893703.6A 2011-08-01 2012-08-01 流感病毒复制抑制剂 Expired - Fee Related CN105503862B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201161513793P 2011-08-01 2011-08-01
US61/513,793 2011-08-01
CN201280043260.6A CN103764654B (zh) 2011-08-01 2012-08-01 流感病毒复制抑制剂

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CN105503862A CN105503862A (zh) 2016-04-20
CN105503862B true CN105503862B (zh) 2018-02-02

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CN201510893703.6A Expired - Fee Related CN105503862B (zh) 2011-08-01 2012-08-01 流感病毒复制抑制剂
CN201280043260.6A Expired - Fee Related CN103764654B (zh) 2011-08-01 2012-08-01 流感病毒复制抑制剂
CN201510893692.1A Pending CN105481853A (zh) 2011-08-01 2012-08-01 流感病毒复制抑制剂

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CN201510893692.1A Pending CN105481853A (zh) 2011-08-01 2012-08-01 流感病毒复制抑制剂

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US (5) US9051319B2 (enExample)
EP (2) EP2739623B1 (enExample)
JP (3) JP5917692B2 (enExample)
KR (1) KR101967172B1 (enExample)
CN (3) CN105503862B (enExample)
AP (1) AP3867A (enExample)
AR (1) AR087418A1 (enExample)
AU (2) AU2012290127B2 (enExample)
CA (1) CA2844054C (enExample)
CL (1) CL2014000245A1 (enExample)
CO (1) CO6940412A2 (enExample)
CY (1) CY1118726T1 (enExample)
DK (1) DK2739623T3 (enExample)
EA (3) EA037372B1 (enExample)
EC (1) ECSP14013189A (enExample)
ES (2) ES2618919T3 (enExample)
GE (2) GEP201706698B (enExample)
HK (1) HK1223915A1 (enExample)
HR (1) HRP20170421T1 (enExample)
HU (1) HUE033752T2 (enExample)
IL (2) IL230618A (enExample)
IN (1) IN2014CN00562A (enExample)
LT (1) LT2739623T (enExample)
ME (1) ME02638B (enExample)
MX (1) MX339149B (enExample)
PE (1) PE20141209A1 (enExample)
PH (1) PH12014500257A1 (enExample)
PL (1) PL2739623T3 (enExample)
PT (1) PT2739623T (enExample)
RS (1) RS55858B1 (enExample)
SG (2) SG10201503835TA (enExample)
SI (1) SI2739623T1 (enExample)
TW (3) TWI537268B (enExample)
UA (2) UA118010C2 (enExample)
UY (1) UY34234A (enExample)
WO (1) WO2013019828A1 (enExample)
ZA (2) ZA201400604B (enExample)

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PH12015501678B1 (en) 2009-06-17 2022-07-06 Vertex Pharma Inhibitors of influenza viruses replication
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UA118010C2 (uk) 2011-08-01 2018-11-12 Вертекс Фармасьютікалз Інкорпорейтед Інгібітори реплікації вірусів грипу
US9296727B2 (en) 2013-10-07 2016-03-29 Vertex Pharmaceuticals Incorporated Methods of regioselective synthesis of 2,4-disubstituted pyrimidines
AU2014348752C1 (en) * 2013-11-13 2019-11-21 Vertex Pharmaceuticals Incorporated Methods of preparing inhibitors of influenza viruses replication
JP6615755B2 (ja) 2013-11-13 2019-12-04 バーテックス ファーマシューティカルズ インコーポレイテッド インフルエンザウイルスの複製の阻害剤
CN103922966B (zh) * 2014-04-14 2015-10-21 武汉大学 作为甲型流感病毒抑制剂的甲酰胺和异腈类化合物及其制备与应用
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KR102531340B1 (ko) * 2014-09-08 2023-05-10 얀센 사이언시즈 아일랜드 언리미티드 컴퍼니 인플루엔자 바이러스 감염에 사용하기 위한 피롤로피리미딘
MA40772A (fr) * 2014-10-02 2017-08-08 Vertex Pharma Variants du virus de la grippe a
MA40773A (fr) 2014-10-02 2017-08-08 Vertex Pharma Variants du virus influenza a
JP6704416B2 (ja) * 2015-05-13 2020-06-03 バーテックス ファーマシューティカルズ インコーポレイテッドＶｅｒｔｅｘ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｉｎｃｏｒｐｏｒａｔｅｄ インフルエンザウイルスの複製の阻害剤を調製する方法
WO2016183120A1 (en) * 2015-05-13 2016-11-17 Vertex Pharmaceuticals Incorporated Inhibitors of influenza viruses replication
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CN106854205B (zh) 2015-12-09 2019-07-09 广东东阳光药业有限公司 流感病毒复制抑制剂及其使用方法和用途
DK3400225T3 (da) * 2016-01-07 2022-01-03 Janssen Sciences Ireland Unlimited Co Pentansyrederivater substitueret med pyrrolo-[2,3-b]pyrimidinpyridiner til behandling af influenzavirusinfektioner
DK3405466T3 (da) 2016-01-20 2021-02-01 Janssen Sciences Ireland Unlimited Co Arylsubstituerede pyrimidiner til anvendelse ved influenzavirusinfektion
CN109790158B (zh) * 2016-07-26 2022-06-24 苏州隆博泰药业有限公司 作为jak抑制剂杂环化合物，该化合物的盐类及其治疗用途
WO2018033082A1 (en) 2016-08-16 2018-02-22 Sunshine Lake Pharma Co., Ltd. Inhibitors of influenza virus replication, application methods and uses thereof
CN109641868B (zh) * 2016-08-30 2021-12-03 广东东阳光药业有限公司 流感病毒复制抑制剂及其使用方法和用途
CN106478460B (zh) * 2016-09-28 2018-06-12 衢州学院 一种手性N-Boc-3-氨基-4-芳基-丁酸的合成方法
EP3555095B1 (en) 2016-12-15 2023-04-12 Sunshine Lake Pharma Co., Ltd. Inhibitors of influenza virus replication and uses thereof
US11098042B2 (en) 2017-01-05 2021-08-24 Sunshine Lake Pharma Co., Ltd. Inhibitors of influenza virus replication and uses thereof
CN110446711B (zh) 2017-03-02 2022-02-15 广东东阳光药业有限公司 流感病毒复制抑制剂及其用途
CN111511907A (zh) 2017-03-14 2020-08-07 加利福尼亚大学董事会 对病毒中免疫逃逸功能区域的全基因组鉴定
CN109384783A (zh) * 2017-08-09 2019-02-26 银杏树药业(苏州)有限公司 新型杂环化合物及其作为抗流感病毒抑制剂的医药用途
KR102813547B1 (ko) * 2018-07-27 2025-05-27 코크리스탈 파마, 아이엔씨. 인플루엔자바이러스 복제 억제제로서의 피롤로[2,3-b]피리딘 유도체
CN112979647B (zh) * 2021-03-12 2022-05-20 浙江大学 含氮杂氨基酸的氮杂吲哚衍生物及制备和应用

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GEP201606531B (en) 2016-08-25
AU2016228190A1 (en) 2016-10-27
CA2844054A1 (en) 2013-02-07
EA201692506A2 (ru) 2017-06-30
CO6940412A2 (es) 2014-05-09
KR101967172B1 (ko) 2019-04-09
US10875855B2 (en) 2020-12-29
EA037372B1 (ru) 2021-03-22
CN103764654B (zh) 2016-01-20
EA201500265A1 (ru) 2015-10-30
CN103764654A (zh) 2014-04-30
LT2739623T (lt) 2017-04-10
NZ716783A (en) 2017-08-25
UY34234A (es) 2013-02-28
SG10201503833SA (en) 2015-06-29
PL2739623T3 (pl) 2017-07-31
SG10201503835TA (en) 2015-06-29
MX2014001067A (es) 2014-03-27
AU2012290127A1 (en) 2013-05-02
EA027210B1 (ru) 2017-06-30
EA201490396A1 (ru) 2014-06-30
EA023423B1 (ru) 2016-06-30
EP3147284B1 (en) 2019-09-25
GEP201706698B (en) 2017-07-10
US20160355512A1 (en) 2016-12-08
ZA201409246B (en) 2016-05-25
US9051319B2 (en) 2015-06-09
JP6259855B2 (ja) 2018-01-10
PE20141209A1 (es) 2014-09-19
HK1194736A1 (zh) 2014-10-24
JP2014521688A (ja) 2014-08-28
TW201629061A (zh) 2016-08-16
WO2013019828A1 (en) 2013-02-07
MX339149B (es) 2016-05-13
EP3147284A1 (en) 2017-03-29
DK2739623T3 (en) 2017-04-24
US9394302B2 (en) 2016-07-19
TW201738241A (zh) 2017-11-01
IL230618A (en) 2016-04-21
HK1223914A1 (zh) 2017-08-11
CA2844054C (en) 2020-09-01
TWI619715B (zh) 2018-04-01

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