[go: up one dir, main page]

WO2017198122A1 - Composé anti-grippe à petites molécules, son procédé de préparation et son utilisation - Google Patents

Composé anti-grippe à petites molécules, son procédé de préparation et son utilisation Download PDF

Info

Publication number
WO2017198122A1
WO2017198122A1 PCT/CN2017/084301 CN2017084301W WO2017198122A1 WO 2017198122 A1 WO2017198122 A1 WO 2017198122A1 CN 2017084301 W CN2017084301 W CN 2017084301W WO 2017198122 A1 WO2017198122 A1 WO 2017198122A1
Authority
WO
WIPO (PCT)
Prior art keywords
group
substituted
membered
unsaturated
saturated
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.)
Ceased
Application number
PCT/CN2017/084301
Other languages
English (en)
Chinese (zh)
Inventor
杨胜勇
魏于全
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.)
Sichuan University
Original Assignee
Sichuan University
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 Sichuan University filed Critical Sichuan University
Priority to CN201780013432.8A priority Critical patent/CN109071567B/zh
Publication of WO2017198122A1 publication Critical patent/WO2017198122A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Images

Classifications

    • 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
    • A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
    • 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
    • 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
    • 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

Definitions

  • X is a halogen
  • L is a saturated or unsaturated 5- to 6-membered heterocycloalkyl group, a saturated or unsaturated C5-C8 cycloalkyl group
  • the hetero atom of the 5- to 6-membered heterocycloalkyl group is N.
  • intermediate 2 is catalyzed by a transition metal, and reacted with a borate reagent in the presence of a base to obtain intermediate 3;
  • the transition metal is Pd 4 (PPh 3 ) 4 , PdAc 2 , Pd 2 (dba) 3 And any one of Pd(PPh 3 ) 2 Cl 2 , Pd(PPh 3 ) 2 Cl 2 DCM, etc.;
  • the borate reagent is boronic acid pinacol ester;
  • the base is KOAc, K 2 CO 3 , Na 2 CO 3 , Cs 2 CO 3 or the like;
  • the molar ratio of the intermediate 2 to the transition metal, the borate reagent, and the base is 1..0.05-0.2..1.5-2..2 ⁇ 4;
  • the temperature of the reaction is from 60 ° C to 90 ° C; the reaction time is from 0.5 h to 24 h.
  • the present invention also provides a pharmaceutically acceptable hydrate of the above-mentioned anti-influenza small molecule compound.
  • hydrate means a compound that further binds stoichiometric or non-stoichiometric amounts of water by non-covalent intermolecular forces.
  • VX-787((2S,3S)-3-((5-fluoro-2-(5-fluoro-1H-pyrrole[2,3-b]pyridin-3-yl)pyrimidin-4-yl)amino) Ring [2.2.2] octane-2-carboxylic acid) is from the State Key Laboratory of Biotherapy of Sichuan University.
  • Influenza virus NA is an enzymatically active surface glycoprotein. At the end of viral infection, it can hydrolyze HA-SA glycosidic bonds, cut off the connection between virus and host cells, and plays an important role in the release and spread of influenza virus.
  • MUNANA is a specific fluorescent substrate for influenza virus NA.
  • the catalytic product produced by the action of NA can produce fluorescence under the irradiation of excitation light. The change of fluorescence intensity can reflect the activity and quantity of NA sensitively and reflect the flow indirectly. The virus is proliferated.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)

Abstract

L'invention se rapporte au domaine de la médecine chimique, et concerne en particulier un composé antigrippe à petites molécules, son procédé de préparation et son utilisation. Les problèmes techniques à résoudre par l'invention sont qu'il n'existe à l'heure actuelle qu'un petit nombre et peu de types de médicaments antigrippe utilisables cliniquement, et les médicaments antigrippe présentent une résistance aux médicaments, une marge thérapeutique étroite, d'importants effets secondaires toxiques, une efficacité clinique médiocre, etc. La solution de l'invention pour résoudre ces problèmes techniques consiste à mettre en oeuvre un composé antigrippe à petites molécules dont la structure est indiquée dans la formule I. L'invention concerne également un procédé de préparation et une utilisation du composé antigrippe à petites molécules. Le composé de l'invention peut vaincre les problèmes de résistance aux médicaments, de faible efficacité, et de marge thérapeutique étroite de l'inhibiteur de la neuraminidase et de l'inhibiteur du canal ionique M2 et d'autres médicaments utilisés cliniquement, et présente une grande valeur de développement.
PCT/CN2017/084301 2016-05-19 2017-05-15 Composé anti-grippe à petites molécules, son procédé de préparation et son utilisation Ceased WO2017198122A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201780013432.8A CN109071567B (zh) 2016-05-19 2017-05-15 抗流感小分子化合物及其制备方法和用途

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN201610334744 2016-05-19
CN201610334744.6 2016-05-19

Publications (1)

Publication Number Publication Date
WO2017198122A1 true WO2017198122A1 (fr) 2017-11-23

Family

ID=60326421

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2017/084301 Ceased WO2017198122A1 (fr) 2016-05-19 2017-05-15 Composé anti-grippe à petites molécules, son procédé de préparation et son utilisation

Country Status (2)

Country Link
CN (1) CN109071567B (fr)
WO (1) WO2017198122A1 (fr)

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2018200425A1 (fr) * 2017-04-24 2018-11-01 Cocrystal Pharma, Inc. Dérivés de pyrrolopyrimidine utiles en tant qu'inhibiteurs de la réplication du virus de la grippe
US10501444B2 (en) 2016-08-16 2019-12-10 Sunshine Lake Pharma Co., Ltd. Inhibitors of influenza virus replication, application methods and uses thereof
US10647693B2 (en) 2016-08-30 2020-05-12 North & South Brother Pharmacy Investment Company Limited Inhibitors of influenza virus replication, application methods and uses thereof
US10927118B2 (en) 2017-03-02 2021-02-23 Sunshine Lake Pharma Co., Ltd. Inhibitors of influenza virus replication and uses thereof
US10987354B2 (en) 2016-12-15 2021-04-27 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
CN113767100A (zh) * 2019-03-01 2021-12-07 锐新医药公司 双环杂芳基化合物及其用途
WO2022263801A1 (fr) * 2021-06-15 2022-12-22 Johnson Matthey Public Limited Company Procédé de préparation de pexidartinib

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005095400A1 (fr) * 2004-03-30 2005-10-13 Vertex Pharmaceuticals Incorporated Azaindoles utiles comme inhibiteurs de janus kinases et d'autres proteines kinases
WO2007084557A2 (fr) * 2006-01-17 2007-07-26 Vertex Pharmaceuticals Incorporated Azaindoles utiles comme inhibiteurs de janus kinases
WO2010148197A1 (fr) * 2009-06-17 2010-12-23 Vertex Pharmaceuticals Incorporated Inhibiteurs de la réplication des virus de la grippe

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3362451B1 (fr) * 2015-12-09 2023-04-12 Sunshine Lake Pharma Co., Ltd. Inhibiteurs de réplication du virus de l'influenza, méthodes d'application et utilisations associées

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005095400A1 (fr) * 2004-03-30 2005-10-13 Vertex Pharmaceuticals Incorporated Azaindoles utiles comme inhibiteurs de janus kinases et d'autres proteines kinases
WO2007084557A2 (fr) * 2006-01-17 2007-07-26 Vertex Pharmaceuticals Incorporated Azaindoles utiles comme inhibiteurs de janus kinases
WO2010148197A1 (fr) * 2009-06-17 2010-12-23 Vertex Pharmaceuticals Incorporated Inhibiteurs de la réplication des virus de la grippe

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10501444B2 (en) 2016-08-16 2019-12-10 Sunshine Lake Pharma Co., Ltd. Inhibitors of influenza virus replication, application methods and uses thereof
US10647693B2 (en) 2016-08-30 2020-05-12 North & South Brother Pharmacy Investment Company Limited Inhibitors of influenza virus replication, application methods and uses thereof
US10987354B2 (en) 2016-12-15 2021-04-27 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
US10927118B2 (en) 2017-03-02 2021-02-23 Sunshine Lake Pharma Co., Ltd. Inhibitors of influenza virus replication and uses thereof
WO2018200425A1 (fr) * 2017-04-24 2018-11-01 Cocrystal Pharma, Inc. Dérivés de pyrrolopyrimidine utiles en tant qu'inhibiteurs de la réplication du virus de la grippe
CN110637022A (zh) * 2017-04-24 2019-12-31 共晶制药公司 可作为流感病毒复制抑制剂的吡咯并嘧啶衍生物
US11014941B2 (en) 2017-04-24 2021-05-25 Cocrystal Pharma, Inc. Pyrrolopyrimidine derivatives useful as inhibitors of influenza virus replication
EA039181B1 (ru) * 2017-04-24 2021-12-15 Кокристал Фарма, Инк. Производные пирролопиримидина, пригодные в качестве ингибиторов репликации вируса гриппа
CN113767100A (zh) * 2019-03-01 2021-12-07 锐新医药公司 双环杂芳基化合物及其用途
WO2022263801A1 (fr) * 2021-06-15 2022-12-22 Johnson Matthey Public Limited Company Procédé de préparation de pexidartinib

Also Published As

Publication number Publication date
CN109071567B (zh) 2021-03-23
CN109071567A (zh) 2018-12-21

Similar Documents

Publication Publication Date Title
WO2017198122A1 (fr) Composé anti-grippe à petites molécules, son procédé de préparation et son utilisation
RU2770096C1 (ru) Полициклические производные карбамоилпиридона, фармацевтические композиции и их применение
CN103450077B (zh) IRE-1α抑制剂
CN102325771B (zh) 作为jnk调节剂的咪唑并[1,2-a]吡啶类
CN107074880A (zh) 二氢吡啶并吡嗪‑1,8‑二酮和它们在治疗、改善或预防病毒疾病中的用途
CN103958521A (zh) 嘧啶-4-酮衍生物及其在治疗、减轻或预防病毒疾病中的用途
CN113563319A (zh) 具有磷酸二酯酶4b抑制活性的吲唑杂环类化合物
WO2022116714A1 (fr) Composé et son utilisation médicale pour une pneumonie à nouveau coronavirus
WO2025007938A1 (fr) Classe d'inhibiteurs de mort cellulaire programmée, son procédé de préparation et son utilisation
CN114874204B (zh) 靶向SARS-CoV-2 3C蛋白酶的PROTAC分子及其应用
WO2022143424A1 (fr) Dérivé de pyridone polycyclique, composition pharmaceutique et utilisation associées
CN112771048B (zh) 流感病毒复制抑制剂及其中间体和用途
CN103360398A (zh) 一种三唑并嘧啶类hiv-1逆转录酶抑制剂及其制备方法与应用
CN109280032B (zh) 一种哒嗪酮母核结构的组蛋白去乙酰化酶抑制剂及其制备方法和用途
CN115947716A (zh) 一种靶向Nur77的吲哚衍生物及其应用
WO2023142518A1 (fr) Composé d'acide hydroxynaphtalénone-phénylboronique, procédé de préparation et utilisation
CN109369623A (zh) 一种取代1,2,3三氮唑类二芳基嘧啶衍生物及其制备方法与应用
CN117279909A (zh) 新型肝选择性聚腺苷酸化聚合酶抑制剂及其使用方法
CN118076589A (zh) 一种酰胺类化合物、其制备方法和制药用途
CN114621204B (zh) 一种含有嘧啶二酮酰基多取代哌嗪类衍生物及其制备方法与应用
CN108727377A (zh) 3-氰基吡唑并[1,5-a]嘧啶衍生物及其制备方法和用途
JP2022516922A (ja) フッ素含有置換ベンゾチオフェン化合物ならびにその医薬組成物および応用
CN112679409B (zh) 一种4-吲哚-取代硫半脲衍生物及其制备方法和应用
CN110437156A (zh) 丹皮酚二氢嘧啶酮类衍生物及其制备方法和应用
CN102688250A (zh) 偶氮类衍生物做为rsk2抑制剂的合成及应用

Legal Events

Date Code Title Description
NENP Non-entry into the national phase

Ref country code: DE

121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 17798685

Country of ref document: EP

Kind code of ref document: A1

122 Ep: pct application non-entry in european phase

Ref document number: 17798685

Country of ref document: EP

Kind code of ref document: A1