2-chloro-5,10-dihydro-3,4,5,10-tetraaza-dibenzo[a,d]cyclohepten-11-one | 920024-87-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯二氮卓类
• 英文名称: 2-chloro-5,10-dihydro-3,4,5,10-tetraaza-dibenzo[a,d]cyclohepten-11-one
• 英文别名: 3-chloro-6,11-dihydropyridazino[3,4-b][1,5]benzodiazepin-5-one
• CAS: 920024-87-9
• 化学式: C₁₁H₇ClN₄O
• 分子量: 246.656
• InChiKey: AEZICWXXUCODMN-UHFFFAOYSA-N

物化性质

• 沸点：
  432.0±45.0 °C(Predicted)
• 密度：
  1.444±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  17
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  66.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-chloro-5,10-dihydro-3,4,5,10-tetraaza-dibenzo[a,d]cyclohepten-11-one 在 氢溴酸 作用下， 以 水 为溶剂， 反应 63.0h， 以36%的产率得到2-bromo-5,10-dihydro-3,4,5,10-tetraaza-dibenzo[a,d]cyclohepten-11-one
  参考文献：
  名称：

  WO2007/6566

  摘要：

  公开号：

文献信息

• Pyridazine Compounds as Glycogen Synthase Kinase 3 Inhibitors
  申请人：Turner Sean C.

  公开号：US20090325937A1

  公开（公告）日：2009-12-31

  Disclosed are pyridazine compounds of the formula I which are useful for inhibiting glycogen synthase kinase 3 (GSK-3), methods of making the compounds, compositions containing the compounds, and methods of treatment using the compounds: In formula I indicates a single bond or a double bond; X is O, S or N—R 5 ; R 1 , R 2 are independently selected from the group consisting of H, NH 2 , NH—C 1 -C 6 -alkyl, OH, ═O, (i.e. a carbonyl group), C 1 -C 6 -alkoxy, halogen, methyl, C 2 -C 4 -alkyl, C 3 -C 4 -cycloalkyl, C 3 -C 4 -alkenyl, fluorinated C 1 -C 4 -alkyl, fluorinated C 3 -C 4 -cycloalkyl, fluorinated C 3 -C 4 -alkenyl, formyl, C 1 -C 3 -alkylcarbonyl, and an aromatic radical Ar, R 1 and R 2 together with the carbon atoms, to which they are attached, form a fused, saturated or unsaturated 5-, 6- or 7-membered C-bound carbocyclic or heterocyclic ring comprising 1 heteroatom, selected from nitrogen, oxygen and sulfur as ring member and 0, 1 or 2 further heteroatoms, independently selected from O, S and N, as ring members, wherein the fused ring is unsubstituted or may carry 1, 2 or 3 substituents selected, independently of each other, from the group of radicals R 4 as defined below; R 3 is hydrogen OH, halogen, CN, nitro, C 1 -C 6 -alkyl, fluorinated C 1 -C 6 -alkyl, C 1 -C 6 -hydroxyalkyl, C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, fluorinated C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 3 -C 7 -cycloalkyl, fluorinated C 3 -C 7 -cycloalkyl, C 1 -C 6 -alkoxy, C 1 -C 6 -hydroxyalkoxy, C 1 -C 6 -alkoxy-C 1 -C 6 -alkoxy, fluorinated C 1 -C 6 -alkoxy, C 1 -C 6 -alkylthio, fluorinated C 1 -C 6 -alkylthio, C 1 -C 6 -alkylsulfinyl, fluorinated C 1 -C 6 -alkylsulfinyl, C 1 -C 6 -alkylsulfonyl, fluorinated C 1 -C 6 -alkylsulfonyl, C 1 -C 6 -alkylcarbonyl, fluorinated C 1 -C 6 -alkylcarbonyl, C 1 -C 6 -alkylcarbonylamino, fluorinated C 1 -C 6 -alkylcarbonylamino, carboxy, C 1 -C 6 -alkyloxycarbonyl, fluorinated C 1 -C 6 -alkoxycarbonyl, NR a R b , C(O)—NR e R f , NH—C(O)—NR e R f , NR a R b —C 1 -C 6 -alkylene, O—NR a R b , etc. and wherein R 4 and R 5 are as defined in the specification and the claims.

  本发明涉及一种公式I的吡嗪化合物，其用于抑制糖原合成酶激酶3（GSK-3），制备该化合物的方法，包含该化合物的组合物以及使用该化合物的治疗方法： 在公式I中， 表示单键或双键； X是O，S或N—R5； R1，R2独立选择自H，NH2，NH—C1-C6-烷基，OH，═O（即羰基），C1-C6-烷氧基，卤素，甲基，C2-C4-烷基，C3-C4-环烷基，C3-C4-烯基，氟代C1-C4-烷基，氟代C3-C4-环烷基，氟代C3-C4-烯基，甲酰基，C1-C3-烷基羰基和芳基基团，R1和R2与它们附着的碳原子一起形成一个融合的、饱和或不饱和的5、6或7元素C-键环或杂环，其中该融合环未被取代或可带有1、2或3个取代基，其独立选择自下面定义的R4基团； R3是氢、羟基、卤素、氰基、硝基、C1-C6-烷基、氟代C1-C6-烷基、C1-C6-羟基烷基、C1-C6-烷氧基-C1-C6-烷基、C2-C6-烯基、氟代C2-C6-烯基、C2-C6-炔基、C3-C7-环烷基、氟代C3-C7-环烷基、C1-C6-烷氧基、C1-C6-羟基烷氧基、C1-C6-烷氧基-C1-C6-烷氧基、氟代C1-C6-烷氧基、C1-C6-烷基硫基、氟代C1-C6-烷基硫基、C1-C6-烷基亚砜基、氟代C1-C6-烷基亚砜基、C1-C6-烷基磺酰基、氟代C1-C6-烷基磺酰基、C1-C6-烷基羰基、氟代C1-C6-烷基羰基、C1-C6-烷基羰基氨基、氟代C1-C6-烷基羰基氨基、羧基、C1-C6-烷氧羰基、氟代C1-C6-烷氧羰基、NRaRb、C（O）—NReRf、NH—C（O）—NReRf、NRaRb—C1-C6-亚基、O—NRaRb等； 其中R4和R5如规范和要求所定义。
• Pyridazine compounds as glycogen synthase kinase 3 inhibitors
  申请人：Abbott GmbH & Co. KG

  公开号：US07994160B2

  公开（公告）日：2011-08-09

  Disclosed are pyridazine compounds of the formula I which are useful for inhibiting glycogen synthase kinase 3 (GSK-3), methods of making the compounds, compositions containing the compounds, and methods of treatment using the compounds: In formula I indicates a single bond or a double bond; X is O, S or N—R5; R1, R2 are independently selected from the group consisting of H, NH2, NH—C1-C6-alkyl, OH, ═O, (i.e. a carbonyl group), C1-C6-alkoxy, halogen, methyl, C2-C4-alkyl, C3-C4-cycloalkyl, C3-C4-alkenyl, fluorinated C1-C4-alkyl, fluorinated C3-C4-cycloalkyl, fluorinated C3-C4-alkenyl, formyl, C1-C3-alkylcarbonyl, and an aromatic radical Ar, R1 and R2 together with the carbon atoms, to which they are attached, form a fused, saturated or unsaturated 5-, 6- or 7-membered C-bound carbocyclic or heterocyclic ring comprising 1 heteroatom, selected from nitrogen, oxygen and sulfur as ring member and 0, 1 or 2 further heteroatoms, independently selected from O, S and N, as ring members, wherein the fused ring is unsubstituted or may carry 1, 2 or 3 substituents selected, independently of each other, from the group of radicals R4 as defined below; R3 is hydrogen OH, halogen, CN, nitro, C1-C6-alkyl, fluorinated C1-C6-alkyl, C1-C6-hydroxyalkyl, C1-C6-alkoxy-C1-C6-alkyl, C2-C6-alkenyl, fluorinated C2-C6-alkenyl, C2-C6-alkynyl, C3-C7-cycloalkyl, fluorinated C3-C7-cycloalkyl, C1-C6-alkoxy, C1-C6-hydroxyalkoxy, C1-C6-alkoxy-C1-C6-alkoxy, fluorinated C1-C6-alkoxy, C1-C6-alkylthio, fluorinated C1-C6-alkylthio, C1-C6-alkylsulfinyl, fluorinated C1-C6-alkylsulfinyl, C1-C6-alkylsulfonyl, fluorinated C1-C6-alkylsulfonyl, C1-C6-alkylcarbonyl, fluorinated C1-C6-alkylcarbonyl, C1-C6-alkylcarbonylamino, fluorinated C1-C6-alkylcarbonylamino, carboxy, C1-C6-alkyloxycarbonyl, fluorinated C1-C6-alkoxycarbonyl, NRaRb, C(O)—NReRf, NH—C(O)—NReRf, NRaRb—C1-C6-alkylene, O—NRaRb, etc. and wherein R4 and R5 are as defined in the specification and the claims.

  本发明涉及一种式子I的吡啶二氮化合物，其可用于抑制糖原合酶激酶3（GSK-3），制备该化合物的方法，含有该化合物的组合物以及使用该化合物的治疗方法：在式子I中，表示单键或双键；X为O、S或N-R5；R1、R2独立地选自H、NH2、NH-C1-C6-烷基、OH、═O（即羰基）、C1-C6-烷氧基、卤素、甲基、C2-C4-烷基、C3-C4-环烷基、C3-C4-烯基、氟化C1-C4-烷基、氟化C3-C4-环烷基、氟化C3-C4-烯基、甲酰基、C1-C3-烷基羰基和芳基Ar，其中R1和R2与它们连接的碳原子一起形成一个融合的、饱和的或不饱和的5、6或7元的碳键环或杂环，包含1个杂原子，选自氮、氧和硫作为环成员，以及0、1或2个进一步的杂原子，独立地选自O、S和N作为环成员，其中融合环未被取代或可能携带1、2或3个取代基，独立地选自以下定义的基团R4；R3为氢、OH、卤素、CN、硝基、C1-C6-烷基、氟化C1-C6-烷基、C1-C6-羟基烷基、C1-C6-烷氧基-C1-C6-烷基、C2-C6-烯基、氟化C2-C6-烯基、C2-C6-炔基、C3-C7-环烷基、氟化C3-C7-环烷基、C1-C6-烷氧基、C1-C6-羟基烷氧基、C1-C6-烷氧基-C1-C6-烷氧基、氟化C1-C6-烷氧基、C1-C6-烷基硫基、氟化C1-C6-烷基硫基、C1-C6-烷基亚砜基、氟化C1-C6-烷基亚砜基、C1-C6-烷基磺酰基、氟化C1-C6-烷基磺酰基、C1-C6-烷基羰基、氟化C1-C6-烷基羰基、C1-C6-烷基羰基氨基、氟化C1-C6-烷基羰基氨基、羧基、C1-C6-烷氧羰基、氟化C1-C6-烷氧羰基、NRaRb、C（O）-NReRf、NH-C（O）-NReRf、NRaRb-C1-C6-亚基、O-NRaRb等，其中R4和R5如规范和权利要求所定义。
• PYRIDAZINE COMPOUNDS AS GLYCOGEN SYNTHASE KINASE 3 INHIBITORS
  申请人：Abbott GmbH & Co. KG

  公开号：EP1902055A1

  公开（公告）日：2008-03-26
• US7994160B2
  申请人：——

  公开号：US7994160B2

  公开（公告）日：2011-08-09
• [EN] PYRIDAZINE COMPOUNDS AS GLYCOGEN SYNTHASE KINASE 3 INHIBITORS<br/>[FR] COMPOSES PYRIDAZINE UTILISES COMME INHIBITEURS DE LA GLYCOGENE SYNTHASE KINASE 3
  申请人：ABBOTT GMBH & CO KG

  公开号：WO2007006566A1

  公开（公告）日：2007-01-18

  [EN] Disclosed are pyridazine compounds of the formula I which are useful for inhibiting glycogen synthase kinase 3 (GSK-3), methods of making the compounds, compositions containing the compounds, and methods of treatment using the compounds: In formula (I) indicates a single bond or a double bond; X is O, S or N-R⁵; R¹, R² are independently selected from the group consisting of H, NH², NH-C₁-C₆-alkyl, OH, =O, (i.e. a carbonyl group), C₁-C₆-alkoxy, halogen, methyl, C₂-C₄-alkyl, C₃- C₄-cycloalkyl, C₃-C₄-alkenyl, fluorinated C₁-C₄-alkyl, fluorinated C₃-C₄-cycloalkyl, fluorinated C₃-C₄-alkenyl, formyl, C₁-C₃-alkylcarbonyl, and an aromatic radical Ar, R₁ and R₂ together with the carbon atoms, to which they are attached, form a fused, saturated or unsaturated 5-, 6- or 7-membered C-bound carbocyclic or heterocyclic ring comprising 1 heteroatom, selected from nitrogen, oxygen and sulfur as ring member and O, 1 or 2 further heteroatoms, independently selected from O, S and N, as ring members, wherein the fused ring is unsubstituted or may carry 1 , 2 or 3 substituents selected, independently of each other, from the group of radicals R⁴ as defined below; R³ is hydrogen OH, halogen, CN, nitro, C₁-C₆-alkyl, fluorinated C₁-C₆-alkyl, C₁-C₆- hydroxyalkyl, C₁-C₆-alkoxy-C₁-C₆-alkyl, C₂-C₆-alkenyl, fluorinated C₂-C₆-alkenyl, C₂-C₆-alkynyl, C₃-C₇-cycloalkyl, fluorinated C₃-C₇-cycloalkyl, C₁-C₆-alkoxy, C₁-C₆- hydroxyalkoxy, C₁C₆-alkoxy-C₁-C₆-alkoxy, fluorinated C₁-C₆-alkoxy, C₁-C₆- alkylthio, fluorinated-C₁-C₆ alkylthio, C₁C₆-alkylsulfinyl, fluorinated C₁-C₆- alkylsulfinyl, C₁-C₆-alkylsulfonyl, fluorinated C₁-C₆ alkylsulfonyl, C₁C₆- alkylcarbonyl, fluorinated C₁C₆-alkylcarbonyl, C₁
  [FR] L'invention porte sur des composés pyridazine de la formule (1) qui sont utilisés pour inhiber la glycogène synthase kinase 3 (GSK-3), sur des procédés de fabrication desdits composés, sur des compositions contenant les composés, et sur des procédés de traitement faisant appel auxdits composés. Dans la formule (1),---- indique une liaison simple ou double; X est O, S ou N-R⁵; R¹ et R² sont choisis indépendamment dans le groupe composé de H, NH², NH-C₁-C₆-alkyle, OH, =O, (c'est-à-dire un groupe carbonyle), C₁-C₆-alcoxy, halogène, méthyle, C₂-C₄-alkyle, C₃-C₄-cycloalkyle, C₃-C₄-alcényle, C₁-C₄-alkyle fluoré, C₃-C₄-cycloalkyle fluoré, C₃-C₄-alcényle fluoré, formyle, C₁-C₃-alkylcarbonyle, et un radical aromatique Ar, R₁ et R₂, avec les atomes de carbone auxquels ils sont attachés, forment un noyau carbocyclique ou hétérocyclique lié à C à 5, 6 ou 7 chaînons, saturé ou insaturé, fusionné comprenant comme élément de noyau 1 hétéroatome choisi entre l'azote, l'oxygène et le soufre et 0, 1 ou 2 hétéroatomes supplémentaires, choisis indépendamment entre O, S et N, comme éléments de noyau, le noyau fusionné étant non substitué ou pouvant porter 1, 2 ou 3 substituants choisis, indépendamment l'un de l'autre, dans le groupe de radicaux R⁴ tel que défini ci-après; R³ est hydrogène OH, halogène, CN, nitro, C₁-C₆-alkyle, C₁-C₆-alkyle fluoré, C₁-C₆-hydroxyalkyle, C₁-C₆-alcoxy-C₁-C₆-alkyle, C₂-C₆-alcényle, C₂-C₆-alcényle fluoré, C₂-C₆-alkynyle, C₃-C₇-cycloalkyle, C₃-C₇-cycloalkyle fluoré, C₁-C₆-alcoxy, C₁-C₆-hydroxyalcoxy, C₁C₆-alcoxy-C₁-C₆-alcoxy, C₁-C₆-alcoxy fluoré, C₁-C₆-alkylthio, C₁-C₆-alkylthio fluoré, C₁C₆-alkylsulfinyle, C₁-C₆-alkylsulfinyle fluoré, C₁-C₆-alkylsulfonyle, C₁-C₆-alkylsulfonyle fluoré, C₁C₆-alkylcarbonyle, C₁C₆-alkylcarbonyle fluoré, C₁-C₆-alkylcarbonylamino, C₁-C6-alkylcarbonylamino fluoré, carboxy, C₁-C₆-alkyloxycarbonyle, C₁-C₆-alcoxycarbonyle fluoré, NR^aR^b, C(O)-NR^eR^f, NH-C(O)-N R^eR^f, NR^aR^b-C₁-C₆-alkylène, O-NR^aR^b, etc.; et R⁴ et R⁵ sont tels que définis dans la description et les revendications.