8-溴-1,6-二氮杂萘-2(1H)-酮 | 902837-41-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 中文名称: 8-溴-1,6-二氮杂萘-2(1H)-酮
• 中文别名: 8-溴-1,6-萘啶-2(1H)-酮
• 英文名称: 8-bromo-1,6-naphthyridin-2-ol
• 英文别名: 8-Bromo-1,6-naphthyridin-2(1H)-one；8-bromo-1H-1,6-naphthyridin-2-one
• CAS: 902837-41-6
• 化学式: C₈H₅BrN₂O
• 分子量: 225.044
• InChiKey: QDOLSUHXUOKZJY-UHFFFAOYSA-N

物化性质

• 沸点：
  412.1±45.0 °C(Predicted)
• 密度：
  1.711±0.06 g/cm3(Predicted)
• 稳定性/保质期：
  按规定使用和贮存的物质不会分解，并应避免接触氧化剂。

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  42
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  1-methyl-4-(3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-pyrazole 、 8-溴-1,6-二氮杂萘-2(1H)-酮 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 sodium carbonate 作用下， 以 乙腈 为溶剂， 反应 1.0h， 以80%的产率得到8-(2-methyl-4-(1-methyl-1H-pyrazol-4-yl)phenyl)-1,6-naphthyridin-2-ol
  参考文献：
  名称：

  NOVEL NAPHTHYRIDINES AND ISOQUINOLINES AND THEIR USE AS CDK8/19 INHIBITORS

  摘要：

  本发明涉及萘啶和异喹啉化合物，以及由此组成的药物可接受的组合物，作为CDK8/19的抑制剂，用于治疗与CDK8/19相关疾病。

  公开号：

  US20160016951A1

文献信息

• [EN] SUBSTITUTED MONO- AND POLYAZANAPHTHALENE DERIVATIVES AND THEIR USE<br/>[FR] DÉRIVÉS SUBSTITUÉS DE MONO- ET POLYAZANAPHTHALÈNE ET LEUR UTILISATION
  申请人：BASILEA PHARMACEUTICA AG

  公开号：WO2016128465A1

  公开（公告）日：2016-08-18

  Disclosed are compounds of formula (I) wherein A is CH or N, B is CR or N; and D is CR; R represents hydrogen, OH or NH2; R1 and R2, independently of each other, represent hydrogen, N(R3)2, halogen, cyano, nitro, R4-C1-C4alkyl, R4-C1-C4halogenoalkyl, OH, R4-C1-C4alkoxy, R4-C1-C4halogenoalkoxy, SH, R4-C1-C4alkythio, R4-C1-C4halogenoalkylthio; R3 represents, independently at each occurrence, hydrogen, R4-C1-C4alkyl or R4-C1-C4halogenoalkyl; R3a represents, independently at each occurrence, hydrogen or C1-C4 alkyl; R4 represents, independently at each occurrence, hydrogen, halogen, cyano, OH, SH, NH2, NH(CH3) or N(CH3)2; X represents a group of formula –E- or –E-F-, wherein E and F are different from each other and represent a group selected from –C(R3a)2-, -(C=O)-, -NR3a- and -O- and F is linked to Y, with the proviso that if X represents –E-F- one of E or F represents –C(R3a)2- or -(C=O)-; Y represents a group selected from C1-C6alkyl, mono- or bicyclic C3-C11cycloalkyl, which may be partially unsaturated, mono- or bicyclic 3 to 11-membered heterocycloalkyl, which may be partially unsaturated, a mono- or bicyclic group comprising at least one aryl or heteroaryl cycle, wherein said heterocycloalkyl group and said group comprising at least one heteroaryl cycle comprise one or more heteroatoms selected from nitrogen, oxygen and sulfur and said group Y is either unsubstituted or substituted by one or more substituents and comprises including its substituents one or more than one nitrogen atom having a lone electron pair; and Z represents a mono- or bicyclic group comprising at least one aryl or heteroaryl cycle, said heteroaryl cycle comprising one or more heteroatoms selected from nitrogen, oxygen and sulfur, which aryl or heteroaryl group is unsubstituted or substituted by one or more substituents; including tautomers of said compounds, mixtures of two tautomeric forms of said compounds, and pharmaceutically acceptable salts of said compounds, tautomers thereof or mixtures of two tautomeric forms thereof, preferably with the proviso that Y comprises one or more primary amino group -NH2, when X represents -(C=O)- or –(C=O)-NR3a-, wherein R3a represents hydrogen or C1-C4alkyl; which are useful for the treatment of proliferation disorders or diseases, such as cancer.

  公开的是以下式(I)的化合物，其中A为CH或N，B为CR或N；D为CR；R代表氢、OH或NH2；R1和R2彼此独立地代表氢、N(R3)2、卤素、氰基、硝基、R4-C1-C4烷基、R4-C1-C4卤代烷基、OH、R4-C1-C4烷氧基、R4-C1-C4卤代烷氧基、SH、R4-C1-C4硫代烷基、R4-C1-C4卤代硫代烷基；R3在每次出现时独立地代表氢、R4-C1-C4烷基或R4-C1-C4卤代烷基；R3a在每次出现时独立地代表氢或C1-C4烷基；R4在每次出现时独立地代表氢、卤素、氰基、OH、SH、NH2、NH(CH3)或N(CH3)2；X代表式-E-或-E-F-的基团，其中E和F彼此不同且代表从-C(R3a)2-、-(C=O)-、-NR3a-和-O中选择的基团，F与Y连接，但如果X代表-E-F-，则E或F中的一个代表-C(R3a)2-或-(C=O)-；Y代表从C1-C6烷基、单环或双环C3-C11环烷基（可能部分不饱和）、单环或双环3至11成员杂环烷基（可能部分不饱和）、包含至少一个芳基或杂芳基环的单环或双环基团，其中所述杂环烷基基团和包含至少一个杂芳基环的基团包含从氮、氧和硫中选择的一个或多个杂原子，所述基团Y未取代或被一个或多个取代基取代，包括其取代基中的一个或多个具有孤对电子的氮原子；Z代表包含至少一个芳基或杂芳基环的单环或双环基团，所述杂芳基环包含从氮、氧和硫中选择的一个或多个杂原子，该芳基或杂芳基基团未取代或被一个或多个取代基取代；包括所述化合物的互变异构体、所述化合物的两种互变异构体形式的混合物，以及所述化合物、其互变异构体或其两种互变异构体形式的药学上可接受的盐，其中Y包括一个或多个一级氨基-NH2，当X代表-(C=O)-或-(C=O)-NR3a-时，其中R3a代表氢或C1-C4烷基；这些化合物对于治疗增殖性疾病或疾病，如癌症，是有用的。
• NOVEL NAPHTHRYIDINES AND ISOQUINOLINES AND THEIR USE AS CDK8/19 INHIBITORS
  申请人：Merck Patent GmbH

  公开号：EP3169678A1

  公开（公告）日：2017-05-24
• SUBSTITUTED MONO- AND POLYAZANAPHTHALENE DERIVATIVES AND THEIR USE
  申请人：Basilea Pharmaceutica International AG

  公开号：US20180002321A1

  公开（公告）日：2018-01-04

  Disclosed are compounds of formula (I) wherein A is CH or N, B is CR or N; and D is CR; R represents hydrogen, OH or NH 2 ; R1 and R2, independently of each other, represent hydrogen, N(R3) 2 , halogen, cyano, nitro, R4-C1-C4alkyl, R4-C1-C4halogenoalkyl, OH, R4-C1-C4alkoxy, R4-C1-C4halogenoalkoxy, SH, R4-C1-C4alkythio, R4-C1-C4halogenoalkylthio; R3 represents, independently at each occurrence, hydrogen, R4-C1-C4alkyl or R4-C1-C4halogenoalkyl; R3a represents, independently at each occurrence, hydrogen or C1-C4 alkyl; R4 represents, independently at each occurrence, hydrogen, halogen, cyano, OH, SH, NH 2 , NH(CH 3 ) or N(CH 3 ) 2 ; X represents a group of formula -E- or -E-F—, wherein E and F are different from each other and represent a group selected from —C(R3a)2-, —(C═O)—, —NR3a- and —O— and F is linked to Y, with the proviso that if X represents -E-F— one of E or F represents —C(R3a) 2 - or —(C═O)—; Y represents a group selected from C1-C6alkyl, mono- or bicyclic C3-C11cycloalkyl, which may be partially unsaturated, mono- or bicyclic 3 to 11-membered heterocycloalkyl, which may be partially unsaturated, a mono- or bicyclic group comprising at least one aryl or heteroaryl cycle, wherein said heterocycloalkyl group and said group comprising at least one heteroaryl cycle comprise one or more heteroatoms selected from nitrogen, oxygen and sulfur and said group Y is either unsubstituted or substituted by one or more substituents and comprises including its substituents one or more than one nitrogen atom having a lone electron pair; and Z represents a mono- or bicyclic group comprising at least one aryl or heteroaryl cycle, said heteroaryl cycle comprising one or more heteroatoms selected from nitrogen, oxygen and sulfur, which aryl or heteroaryl group is unsubstituted or substituted by one or more substituents; including tautomers of said compounds, mixtures of two tautomeric forms of said compounds, and pharmaceutically acceptable salts of said compounds, tautomers thereof or mixtures of two tautomeric forms thereof, preferably with the proviso that Y comprises one or more primary amino group —NH 2 , when X represents —(C═O)— or —(C═O)—NR3a-, wherein R3a represents hydrogen or C1-C4alkyl; which are useful for the treatment of proliferation disorders or diseases, such as cancer.
• [EN] NOVEL NAPHTHRYIDINES AND ISOQUINOLINES AND THEIR USE AS CDK8/19 INHIBITORS<br/>[FR] NOUVELLES NAPHTYRIDINES ET ISOQUINOLÉINES ET LEUR UTILISATION À TITRE D'INHIBITEURS DE CDK8/19
  申请人：MERCK PATENT GMBH

  公开号：WO2016009076A1

  公开（公告）日：2016-01-21

  The present invention relates to naphthyridine and isoquinoline compounds, and pharmaceutically acceptable compositions thereof, useful as inhibitors of CDK8/19, and for the treatment of CDK8/19-related disorders.
• NOVEL NAPHTHYRIDINES AND ISOQUINOLINES AND THEIR USE AS CDK8/19 INHIBITORS
  申请人：Merck Patent GmbH

  公开号：US20160016951A1

  公开（公告）日：2016-01-21

  The present invention relates to naphthyridine and isoquinoline compounds, and pharmaceutically acceptable compositions thereof, useful as inhibitors of CDK8/19, and for the treatment of CDK8/19-related disorders.

  本发明涉及萘啶和异喹啉化合物，以及由此组成的药物可接受的组合物，作为CDK8/19的抑制剂，用于治疗与CDK8/19相关疾病。