WO2014111031A1 - Composé triazine, sel pharmaceutique, isomère, ou hydrate de celui-ci, et composition pharmaceutique de celui-ci - Google Patents

Composé triazine, sel pharmaceutique, isomère, ou hydrate de celui-ci, et composition pharmaceutique de celui-ci Download PDF

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Publication number
WO2014111031A1
WO2014111031A1 PCT/CN2014/070733 CN2014070733W WO2014111031A1 WO 2014111031 A1 WO2014111031 A1 WO 2014111031A1 CN 2014070733 W CN2014070733 W CN 2014070733W WO 2014111031 A1 WO2014111031 A1 WO 2014111031A1
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WO
WIPO (PCT)
Prior art keywords
compound
group
alkyl
heterocyclyl
hydrate
Prior art date
Application number
PCT/CN2014/070733
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English (en)
Chinese (zh)
Inventor
李育飞
阙灵
Original Assignee
四川恒康发展有限责任公司
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 四川恒康发展有限责任公司 filed Critical 四川恒康发展有限责任公司
Priority to CN201480003555.XA priority Critical patent/CN104870437A/zh
Publication of WO2014111031A1 publication Critical patent/WO2014111031A1/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • 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]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D253/00—Heterocyclic compounds containing six-membered rings having three nitrogen atoms as the only ring hetero atoms, not provided for by group C07D251/00
    • C07D253/02—Heterocyclic compounds containing six-membered rings having three nitrogen atoms as the only ring hetero atoms, not provided for by group C07D251/00 not condensed with other rings
    • C07D253/06—1,2,4-Triazines
    • C07D253/065—1,2,4-Triazines having three double bonds between ring members or between ring members and non-ring members
    • C07D253/07—1,2,4-Triazines 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D253/00—Heterocyclic compounds containing six-membered rings having three nitrogen atoms as the only ring hetero atoms, not provided for by group C07D251/00
    • C07D253/02—Heterocyclic compounds containing six-membered rings having three nitrogen atoms as the only ring hetero atoms, not provided for by group C07D251/00 not condensed with other rings
    • C07D253/06—1,2,4-Triazines
    • C07D253/065—1,2,4-Triazines having three double bonds between ring members or between ring members and non-ring members
    • C07D253/07—1,2,4-Triazines 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
    • C07D253/075—Two hetero atoms, in positions 3 and 5
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • 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
    • C07D471/10—Spiro-condensed systems
    • 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
    • C07D487/10—Spiro-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/10—Spiro-condensed systems
    • C07D491/107—Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
    • 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
    • C07F9/06—Phosphorus compounds without P—C bonds
    • C07F9/22—Amides of acids of phosphorus
    • C07F9/224—Phosphorus triamides

Definitions

  • X is selected from N, CH or 0.
  • R 2 , R 3 or R 4 are independently selected from the group consisting of H, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, methyl, ethyl, propyl, butyl, vinyl, Propylene, butenyl, trifluoromethyl, trifluoroethyl, chloromethyl, chloroethyl, methoxy, ethyloxy, methylcarbonyl, ethylcarbonyl, piperidinyl, piperazinyl, Pyrrolyl, imidazolyl, pyrazolyl, pyrrolidinyl, pyrrolyl, dihydropyrrolyl, pyrrolinyl, imidazolidinyl, imidazolinyl, pyrazolidinyl, quinolinyl, benzofuranyl, pyrazine Base, pyrazolinyl, thiadiazolyl, hydroxy, cyano,
  • Compounds of the invention include, but are not limited to, the following compounds: Compound 1
  • the compound of the present invention and a pharmaceutically acceptable salt thereof, or an isomer thereof, or a hydrate thereof and/or composition thereof, may be formulated together with a pharmaceutically acceptable excipient or carrier, and the resulting composition may be administered in vivo.
  • Mammals such as men, women, and animals, are used to treat conditions, symptoms, and diseases.
  • the composition may be: a tablet, a pill, a suspension, a solution, an emulsion, a capsule, an aerosol, a sterile injectable solution. Sterile powder, etc.
  • the amount of the compound or pharmaceutical composition of the invention administered to a patient is not fixed and is usually administered in a pharmaceutically effective amount.
  • the amount of the compound actually administered can be determined by the physician on a case-by-case basis, including the condition being treated, the route of administration selected, the actual compound administered, the individual condition of the patient, and the like.
  • the dosage of the compound of the invention depends on the particular use of the treatment, the mode of administration, the condition of the patient, and the judgment of the physician.
  • the proportion or concentration of the compound of the present invention in the pharmaceutical composition depends on various factors including dosage, physicochemical properties, administration route and the like.
  • the intermediate 2 (0.44 mmol) obtained in Step 1 was dissolved in 10 mL of NMP, and 1.5 eq (0.66 mmol) of m-CPBA was added. After the mixture was stirred at room temperature for 30 min, leq (0.44 mmol) of pTSA and 2 eq ( 0.88 mmol) of 4-morpholinylaniline, the resulting mixture was stirred at 110 ° C for 2-4 h, cooled to room temperature, diluted with more than 100 mL of ethyl acetate, then washed with saturated sodium carbonate solution and then washed with water. Concentration in vacuo and reversed phase HPLC gave compound 27.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Rheumatology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pain & Pain Management (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne un composé triazine, un sel pharmaceutique, un isomère ou un hydrate de celui-ci, une composition pharmaceutique de celui-ci, le procédé de préparation de celui-ci, un procédé de préparation d'une composition pharmaceutique utilisant ce composé et au moins un excipient ou vecteur pharmaceutiquement acceptable, et l'utilisation du composé selon l'invention pour préparer un médicament pour le traitement de plusieurs troubles, symptômes et maladies à médiation par Syk kinase et/ou Jak kinase.
PCT/CN2014/070733 2013-01-17 2014-01-16 Composé triazine, sel pharmaceutique, isomère, ou hydrate de celui-ci, et composition pharmaceutique de celui-ci WO2014111031A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201480003555.XA CN104870437A (zh) 2013-01-17 2014-01-16 三嗪化合物、其药用盐、异构体或水合物及其药物组合物

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN201310017606 2013-01-17
CN201310017606.1 2013-01-17

Publications (1)

Publication Number Publication Date
WO2014111031A1 true WO2014111031A1 (fr) 2014-07-24

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Application Number Title Priority Date Filing Date
PCT/CN2014/070733 WO2014111031A1 (fr) 2013-01-17 2014-01-16 Composé triazine, sel pharmaceutique, isomère, ou hydrate de celui-ci, et composition pharmaceutique de celui-ci

Country Status (2)

Country Link
CN (1) CN104870437A (fr)
WO (1) WO2014111031A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9382246B2 (en) 2013-12-05 2016-07-05 Pharmacyclics Llc Inhibitors of Bruton's tyrosine kinase
CN109293569A (zh) * 2018-11-08 2019-02-01 湘潭大学 一种无催化剂参与的转胺反应制备甲酰胺衍生物的方法

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000076980A1 (fr) * 1999-06-10 2000-12-21 Yamanouchi Pharmaceutical Co., Ltd. Nouveaux derives heterocycliques azotes ou leurs sels
EP1184376A1 (fr) * 1999-06-09 2002-03-06 Yamanouchi Pharmaceutical Co. Ltd. Nouveaux derives carboxamide heterocycliques
WO2013047813A1 (fr) * 2011-09-30 2013-04-04 大鵬薬品工業株式会社 Dérivé de 1,2,4-triazine-6-carboxamide
WO2013171690A1 (fr) * 2012-05-16 2013-11-21 Novartis Ag Dérivés hétéroaryles monocycliques de cycloalkyldiamine
WO2013192049A2 (fr) * 2012-06-22 2013-12-27 Portola Pharmaceuticals, Inc. Inhibiteurs de 1,2,4-triazine-6-carboxamide kinase

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE69839735D1 (de) * 1997-12-15 2008-08-28 Astellas Pharma Inc Pyrimidin-5-carboxamid-derivate

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1184376A1 (fr) * 1999-06-09 2002-03-06 Yamanouchi Pharmaceutical Co. Ltd. Nouveaux derives carboxamide heterocycliques
WO2000076980A1 (fr) * 1999-06-10 2000-12-21 Yamanouchi Pharmaceutical Co., Ltd. Nouveaux derives heterocycliques azotes ou leurs sels
WO2013047813A1 (fr) * 2011-09-30 2013-04-04 大鵬薬品工業株式会社 Dérivé de 1,2,4-triazine-6-carboxamide
WO2013171690A1 (fr) * 2012-05-16 2013-11-21 Novartis Ag Dérivés hétéroaryles monocycliques de cycloalkyldiamine
WO2013192049A2 (fr) * 2012-06-22 2013-12-27 Portola Pharmaceuticals, Inc. Inhibiteurs de 1,2,4-triazine-6-carboxamide kinase

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9382246B2 (en) 2013-12-05 2016-07-05 Pharmacyclics Llc Inhibitors of Bruton's tyrosine kinase
US9656988B2 (en) 2013-12-05 2017-05-23 Pharmacyclics Llc Inhibitors of Bruton's tyrosine kinase
CN109293569A (zh) * 2018-11-08 2019-02-01 湘潭大学 一种无催化剂参与的转胺反应制备甲酰胺衍生物的方法
CN109293569B (zh) * 2018-11-08 2021-08-06 湘潭大学 一种无催化剂参与的转胺反应制备甲酰胺衍生物的方法

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Publication number Publication date
CN104870437A (zh) 2015-08-26

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