WO2021018165A1 - Dérivé pyridine benzamide, son procédé de préparation, et ses applications médicales - Google Patents

Dérivé pyridine benzamide, son procédé de préparation, et ses applications médicales Download PDF

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Publication number
WO2021018165A1
WO2021018165A1 PCT/CN2020/105391 CN2020105391W WO2021018165A1 WO 2021018165 A1 WO2021018165 A1 WO 2021018165A1 CN 2020105391 W CN2020105391 W CN 2020105391W WO 2021018165 A1 WO2021018165 A1 WO 2021018165A1
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WO
WIPO (PCT)
Prior art keywords
pharmaceutically acceptable
general formula
tautomer
racemate
compound represented
Prior art date
Application number
PCT/CN2020/105391
Other languages
English (en)
Chinese (zh)
Inventor
郁楠
杨方龙
徐国际
贺峰
陶维康
Original Assignee
江苏恒瑞医药股份有限公司
上海恒瑞医药有限公司
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 江苏恒瑞医药股份有限公司, 上海恒瑞医药有限公司 filed Critical 江苏恒瑞医药股份有限公司
Publication of WO2021018165A1 publication Critical patent/WO2021018165A1/fr

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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
    • A61K31/435—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
    • 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
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
    • C07D213/72—Nitrogen atoms
    • C07D213/75—Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
    • 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

Definitions

  • the purpose of the present disclosure is to provide a compound represented by general formula (I) or its tautomer, mesoisomer, racemate, enantiomer, diastereomer, or Mixture form or its pharmaceutically acceptable salt:
  • R 4 is selected from hydrogen atom, halogen, alkyl, alkoxy, haloalkyl, hydroxy and hydroxyalkyl;
  • the substituent is preferably independently optionally selected from alkyl, alkenyl, alkynyl , Alkoxy, alkylthio, alkylamino, halogen, thiol, hydroxyl, nitro, cyano, cycloalkyl, heterocyclyl, aryl, heteroaryl, cycloalkoxy, heterocycloalkoxy Substituted by one or more substituents in the group, cycloalkylthio, heterocycloalkylthio and oxo.
  • bridged cycloalkyl refers to a 5- to 20-membered, all-carbon polycyclic group with any two rings sharing two carbon atoms that are not directly connected. It may contain one or more double bonds, but no ring has complete Conjugated ⁇ electron system. It is preferably 6 to 14 yuan, more preferably 7 to 10 yuan (for example, 7, 8, 9 or 10 yuan). It can be classified into bicyclic, tricyclic, tetracyclic or polycyclic bridged cycloalkyls according to the number of constituent rings, preferably bicyclic, tricyclic or tetracyclic, more preferably bicyclic or tricyclic.
  • bridged cycloalkyl groups include:
  • Deuterated reagents include but are not limited to deuterated borane and tri-deuterated. Borane tetrahydrofuran solution, deuterated lithium aluminum hydride, deuterated ethyl iodide and deuterated methyl iodide, etc.
  • SD rats were fasted overnight and then given by gavage.
  • the dose was 2.0 mg/kg and the volume was 10.0 mL/kg.

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

Abstract

Cette invention concerne un dérivé pyridine benzamide, son procédé de préparation, et ses applications médicales. De façon spécifique, la présente invention concerne le dérivé pyridine benzamide représenté par la formule (I), son procédé de préparation, une composition pharmaceutique contenant le dérivé, et ses utilisations en tant qu'agent thérapeutique et spécifiquement en tant qu'inhibiteur de NaV dans le traitement et/ou la soulagement de la douleur et de maladies associées à la douleur. Les substituants de la formule (I) sont tels que définis dans la description.
PCT/CN2020/105391 2019-07-30 2020-07-29 Dérivé pyridine benzamide, son procédé de préparation, et ses applications médicales WO2021018165A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN201910697731.9 2019-07-30
CN201910697731 2019-07-30

Publications (1)

Publication Number Publication Date
WO2021018165A1 true WO2021018165A1 (fr) 2021-02-04

Family

ID=74230279

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2020/105391 WO2021018165A1 (fr) 2019-07-30 2020-07-29 Dérivé pyridine benzamide, son procédé de préparation, et ses applications médicales

Country Status (2)

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TW (1) TW202114989A (fr)
WO (1) WO2021018165A1 (fr)

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102459187A (zh) * 2009-06-11 2012-05-16 弗·哈夫曼-拉罗切有限公司 Janus激酶抑制化合物和方法
CN105026373A (zh) * 2013-01-31 2015-11-04 沃泰克斯药物股份有限公司 作为钠通道调节剂的吡啶酮酰胺
CN105814067A (zh) * 2013-12-13 2016-07-27 沃泰克斯药物股份有限公司 作为钠通道调节剂的吡啶酮酰胺的前药
WO2017075222A1 (fr) * 2015-10-30 2017-05-04 Lieber Institute For Brain Development Traitement de maladies et de troubles neurologiques et neurdéveloppementaux associés à une expression et à une activité aberrante des canaux ioniques
WO2018213426A1 (fr) * 2017-05-16 2018-11-22 Vertex Pharmaceuticals Incorporated Amides de pyridone deutérés et leurs promédicaments utilisés en tant que modulateurs de canaux sodiques

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102459187A (zh) * 2009-06-11 2012-05-16 弗·哈夫曼-拉罗切有限公司 Janus激酶抑制化合物和方法
CN105026373A (zh) * 2013-01-31 2015-11-04 沃泰克斯药物股份有限公司 作为钠通道调节剂的吡啶酮酰胺
CN105814067A (zh) * 2013-12-13 2016-07-27 沃泰克斯药物股份有限公司 作为钠通道调节剂的吡啶酮酰胺的前药
WO2017075222A1 (fr) * 2015-10-30 2017-05-04 Lieber Institute For Brain Development Traitement de maladies et de troubles neurologiques et neurdéveloppementaux associés à une expression et à une activité aberrante des canaux ioniques
WO2018213426A1 (fr) * 2017-05-16 2018-11-22 Vertex Pharmaceuticals Incorporated Amides de pyridone deutérés et leurs promédicaments utilisés en tant que modulateurs de canaux sodiques

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
SCHLÜTER，FRIEDERIKE， ET AL.: "Oxidation differentially modulates the recombinant voltage-gated Na+ channel α-subunits Nav1.7 and Nav1.8，", BRAIN RESEARCH, vol. 1648, 19 July 2016 (2016-07-19), XP029722400, DOI: 20201018141543A *

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