2-methyl-N'-(4-methylbenzoyl)-N’-phenylbenzohydrazide | 1417652-56-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-methyl-N'-(4-methylbenzoyl)-N’-phenylbenzohydrazide
• 英文别名: 2-methyl-N'-(4-methylbenzoyl)-N'-phenylbenzohydrazide
• CAS: 1417652-56-2
• 化学式: C₂₂H₂₀N₂O₂
• 分子量: 344.413
• InChiKey: GQRNBZGZBNSRTJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  49.4
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  对甲基苯甲酸甲酯 、 2-methyl-N′-phenylbenzohydrazide 在 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 生成 2-methyl-N'-(4-methylbenzoyl)-N’-phenylbenzohydrazide
  参考文献：
  名称：

  Preparation and X-Ray Crystal Structure of 3-(4-(Dimethylamino)phenyl)-2-(phenylamino)isoquinolin-1(2H)-one, 3-(4-Methoxyphenyl)-2-(phenylamino)isoquinolin-1(2H)-one, and 2-Methyl-N′-(4-methylbenzoyl)-N′-phenylbenzohydrazide from Polylithiated 2-methylbenzoic Acid Phenylhydrazide and Methyl 4-dimethylaminobenzoate, Methyl 4-methoxybenzoate, or Methyl 4-methylbenzoate

  摘要：

  用过量的二异丙基酰胺锂对 2-甲基苯甲酸苯肼进行多硫化、生成的多硫化中间体与 4-二甲氨基苯甲酸甲酯或 4-甲氧基苯甲酸甲酯缩合，得到 C-酰化中间体，立即进行酸环化，得到 3-(4-(二甲氨基)-苯基)-2-(苯基氨基)异喹啉-1(2H)-酮 C23H21N3O 或 3-(4-甲氧基苯基)-2-(苯基氨基)异喹啉-1(2H)-酮 C22H18N2O2。多硫化中间体在与 4-甲基苯甲酸甲酯缩合时发生 N-酰化反应，生成 2-甲基-N′-（4-甲基苯甲酰基）-N′-苯基苯甲酰肼 C22H20N2O2。C23H21N3O 4a 的晶体呈三菱形，P$\overline{1}$$ ，a = 9.138(2) 埃，b = 10.519(2) Å, c = 11.082(2) Å, α = 91.55(3)°, β = 108.92(3)°, γ = 111.16(3)°, Z = 2, V = 927.1(3) Å3, R 1 = 0.0711 and wR 2 = 0.1828 for reflections with I > 2σ(I); C22H18N2O2 4b 晶体为单斜晶系，P21/c, a = 8.821(1) Å, b = 13.276(2) Å, c = 15.482(3) Å, β = 105.271(4)°, Z = 4, V = 1748.9(5) Å3, R 1 = 0.0416 and wR 2 = 0.1030 for reflections with I > 2σ(I)；C22H20N2O2 3 的晶体为正方体，Pbca，a = 13。505(3) Å, b = 9.733(2) Å, c = 28.601(6) Å, Z = 8, V = 3759.4(13) Å3, R 1 = 0.1683 and wR 2 = 0.3526 for reflections with I > 2σ(I)。X 射线晶体分析对于确认 3-(4-(二甲基氨基)苯基)-2-(苯基氨基)异喹啉-1(2H)-酮 C23H21N3O 4a、3-(4-甲氧基苯基)-2-(苯基氨基)异喹啉-1(2H)-酮 C22H18N2O2 4b、和 2-甲基-N′-(4-甲基苯甲酰基)-N′-苯基苯甲酰肼 C22H20N2O2 3，由多硫化 2-甲基苯甲酸苯甲酰肼和 4-二甲氨基苯甲酸甲酯、4-甲氧基苯甲酸甲酯或 4-甲基苯甲酸甲酯制备。C23H21N3O 4a 的晶体呈三菱形，P$\overline{1}$$ ，a = 9.138(2) 埃，b = 10.519(2) Å, c = 11.082(2) Å, α = 91.55(3)°, β = 108.92(3)°, γ = 111.16(3)°, Z = 2, V = 927.1(3) Å3, R 1 = 0.0711 and wR 2 = 0.1828 for reflections with I > 2σ(I); C22H18N2O2 4b 晶体为单斜晶系，P21/c, a = 8.821(1) Å, b = 13.276(2) Å, c = 15.482(3) Å, β = 105.271(4)°, Z = 4, V = 1748.9(5) Å3, R 1 = 0.0416 and wR 2 = 0.1030 for reflections with I > 2σ(I)；C22H20N2O2 3 的晶体为正方体，Pbca，a = 13。505(3) Å, b = 9.733(2) Å, c = 28.601(6) Å, Z = 8, V = 3759.4(13) Å3, R 1 = 0.1683 and wR 2 = 0.3526 for reflections with I > 2σ(I).

  DOI：

  10.1007/s10870-012-0342-5

文献信息

• 3-ARYL-5-SUBSTITUTED-ISOQUINOLIN-1-ONE COMPOUNDS AND THEIR THERAPEUTIC USE
  申请人：INSTITUTE OF CANCER RESEARCH: ROYAL CANCER HOSPITAL (THE)

  公开号：US20150099732A1

  公开（公告）日：2015-04-09

  The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain 3-aryl-5-substituted-2H-isoquinolin-1-one compounds that, inter alia, inhibit PARP (e.g., PARP1, TNKS1, TNKS2, etc.) and/or Wnt signalling. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit PARP (e.g., PARP1, TNKS1, TNKS2, etc.); to inhibit Wnt signalling; to treat disorders that are ameliorated by the inhibition of PARP (e.g., PARP1, TNKS1, TNKS2, etc.); to treat disorders that are ameliorated by the inhibition of Wnt signalling; to treat proliferative conditions such as cancer, etc.

  本发明通常涉及治疗化合物领域。更具体地，本发明涉及某些3-芳基-5-取代-2H-异喹啉-1-酮化合物，该化合物在抑制PARP（例如PARP1，TNKS1，TNKS2等）和/或Wnt信号传导方面具有作用。本发明还涉及包含这些化合物的药物组合物，以及利用这些化合物和组合物，在体内和体外，来抑制PARP（例如PARP1，TNKS1，TNKS2等）；抑制Wnt信号传导；治疗通过抑制PARP（例如PARP1，TNKS1，TNKS2等）改善的疾病；治疗通过抑制Wnt信号传导改善的疾病；治疗癌症等增生症状。
• US9193689B2
  申请人：——

  公开号：US9193689B2

  公开（公告）日：2015-11-24
• [EN] 3-ARYL-5-SUBSTITUTED-ISOQUINOLIN-1-ONE COMPOUNDS AND THEIR THERAPEUTIC USE<br/>[FR] COMPOSÉS 3-ARYL -5-SUBSTITUÉ-ISOQUINOLIN -1-ONE ET LEUR UTILISATION THÉRAPEUTIQUE
  申请人：CANCER RES INST ROYAL

  公开号：WO2013132253A1

  公开（公告）日：2013-09-12

  The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain 3-aryl-5-substituted- 2H-isoquinolin-1-one compounds that, inter alia, inhibit PARP (e.g., PARP1, TNKS1, TNKS2, etc.) and/or Wnt signalling. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit PARP (e.g., PARP1, TNKS1, TNKS2, etc.); to inhibit Wnt signalling; to treat disorders that are ameliorated by the inhibition of PARP (e.g., PARP1, TNKS1, TNKS2, etc.); to treat disorders that are ameliorated by the inhibition of Wnt signalling; to treat proliferative conditions such as cancer, etc.
• Preparation and X-Ray Crystal Structure of 3-(4-(Dimethylamino)phenyl)-2-(phenylamino)isoquinolin-1(2H)-one, 3-(4-Methoxyphenyl)-2-(phenylamino)isoquinolin-1(2H)-one, and 2-Methyl-N′-(4-methylbenzoyl)-N′-phenylbenzohydrazide from Polylithiated 2-methylbenzoic Acid Phenylhydrazide and Methyl 4-dimethylaminobenzoate, Methyl 4-methoxybenzoate, or Methyl 4-methylbenzoate
  作者：William G. Shuler、Ellyn A. Smith、Sloan M. Hess、Thomas M. C. McFadden、Clyde R. Metz、Donald G. VanDerveer、William T. Pennington、Phillip J. Mabe、Shabree L. Knick、Charles F. Beam

  DOI：10.1007/s10870-012-0342-5

  日期：2012.9

  2-Methylbenzoic acid phenylhydrazide was polylithiated with excess lithium diisopropylamide, and the resulting polylithiated intermediate was condensed with methyl 4-dimethylaminobenzoate or methyl 4-methoxybenzoate to afford C-acylated intermediates that were immediately acid cyclized to afford 3-(4-(dimethylamino)-phenyl)-2-(phenylamino)isoquinolin-1(2H)-one C23H21N3O or 3-(4-methoxyphenyl)-2-(phenylamino)isoquinolin-1(2H)-one C22H18N2O2. The polylithiated intermediate underwent N-acylation when it was condensed with methyl 4-methylbenzoate to give 2-methyl-N′-(4-methylbenzoyl)-N′-phenylbenzohydrazide C22H20N2O2. Crystals of C23H21N3O 4a are triclinic, P $$ \overline1} $$ , a = 9.138(2) Å, b = 10.519(2) Å, c = 11.082(2) Å, α = 91.55(3)°, β = 108.92(3)°, γ = 111.16(3)°, Z = 2, V = 927.1(3) Å3, R 1 = 0.0711 and wR 2 = 0.1828 for reflections with I > 2σ(I); crystals of C22H18N2O2 4b are monoclinic, P21/c, a = 8.821(1) Å, b = 13.276(2) Å, c = 15.482(3) Å, β = 105.271(4)°, Z = 4, V = 1748.9(5) Å3, R 1 = 0.0416 and wR 2 = 0.1030 for reflections with I > 2σ(I); crystals of C22H20N2O2 3 are orthorhombic, Pbca, a = 13.505(3) Å, b = 9.733(2) Å, c = 28.601(6) Å, Z = 8, V = 3759.4(13) Å3, R 1 = 0.1683 and wR 2 = 0.3526 for reflections with I > 2σ(I). X-ray crystal analysis was important for the confirmation of the structure of 3-(4-(dimethylamino)phenyl)-2-(phenylamino)isoquinolin-1(2H)-one C23H21N3O 4a, 3-(4-methoxyphenyl)-2-(phenylamino)isoquinolin-1(2H)-one C22H18N2O2 4b, and 2-methyl-N′-(4-methylbenzoyl)-N′-phenylbenzohydrazide C22H20N2O2 3 prepared from polylithiated 2-methylbenzoicacid phenylhydrazide and methyl 4-dimethylaminobenzoate, methyl 4-methoxybenzoate, or methyl 4-methylbenzoate. Crystals of C23H21N3O 4a are triclinic, P $$ \overline1} $$ , a = 9.138(2) Å, b = 10.519(2) Å, c = 11.082(2) Å, α = 91.55(3)°, β = 108.92(3)°, γ = 111.16(3)°, Z = 2, V = 927.1(3) Å3, R 1 = 0.0711 and wR 2 = 0.1828 for reflections with I > 2σ(I); crystals of C22H18N2O2 4b are monoclinic, P21/c, a = 8.821(1) Å, b = 13.276(2) Å, c = 15.482(3) Å, β = 105.271(4)°, Z = 4, V = 1748.9(5) Å3, R 1 = 0.0416 and wR 2 = 0.1030 for reflections with I > 2σ(I); crystals of C22H20N2O2 3 are orthorhombic, Pbca, a = 13.505(3) Å, b = 9.733(2) Å, c = 28.601(6) Å, Z = 8, V = 3759.4(13) Å3, R 1 = 0.1683 and wR 2 = 0.3526 for reflections with I > 2σ(I).

  用过量的二异丙基酰胺锂对 2-甲基苯甲酸苯肼进行多硫化、生成的多硫化中间体与 4-二甲氨基苯甲酸甲酯或 4-甲氧基苯甲酸甲酯缩合，得到 C-酰化中间体，立即进行酸环化，得到 3-(4-(二甲氨基)-苯基)-2-(苯基氨基)异喹啉-1(2H)-酮 C23H21N3O 或 3-(4-甲氧基苯基)-2-(苯基氨基)异喹啉-1(2H)-酮 C22H18N2O2。多硫化中间体在与 4-甲基苯甲酸甲酯缩合时发生 N-酰化反应，生成 2-甲基-N′-（4-甲基苯甲酰基）-N′-苯基苯甲酰肼 C22H20N2O2。C23H21N3O 4a 的晶体呈三菱形，P$\overline1}$$ ，a = 9.138(2) 埃，b = 10.519(2) Å, c = 11.082(2) Å, α = 91.55(3)°, β = 108.92(3)°, γ = 111.16(3)°, Z = 2, V = 927.1(3) Å3, R 1 = 0.0711 and wR 2 = 0.1828 for reflections with I > 2σ(I); C22H18N2O2 4b 晶体为单斜晶系，P21/c, a = 8.821(1) Å, b = 13.276(2) Å, c = 15.482(3) Å, β = 105.271(4)°, Z = 4, V = 1748.9(5) Å3, R 1 = 0.0416 and wR 2 = 0.1030 for reflections with I > 2σ(I)；C22H20N2O2 3 的晶体为正方体，Pbca，a = 13。505(3) Å, b = 9.733(2) Å, c = 28.601(6) Å, Z = 8, V = 3759.4(13) Å3, R 1 = 0.1683 and wR 2 = 0.3526 for reflections with I > 2σ(I)。X 射线晶体分析对于确认 3-(4-(二甲基氨基)苯基)-2-(苯基氨基)异喹啉-1(2H)-酮 C23H21N3O 4a、3-(4-甲氧基苯基)-2-(苯基氨基)异喹啉-1(2H)-酮 C22H18N2O2 4b、和 2-甲基-N′-(4-甲基苯甲酰基)-N′-苯基苯甲酰肼 C22H20N2O2 3，由多硫化 2-甲基苯甲酸苯甲酰肼和 4-二甲氨基苯甲酸甲酯、4-甲氧基苯甲酸甲酯或 4-甲基苯甲酸甲酯制备。C23H21N3O 4a 的晶体呈三菱形，P$\overline1}$$ ，a = 9.138(2) 埃，b = 10.519(2) Å, c = 11.082(2) Å, α = 91.55(3)°, β = 108.92(3)°, γ = 111.16(3)°, Z = 2, V = 927.1(3) Å3, R 1 = 0.0711 and wR 2 = 0.1828 for reflections with I > 2σ(I); C22H18N2O2 4b 晶体为单斜晶系，P21/c, a = 8.821(1) Å, b = 13.276(2) Å, c = 15.482(3) Å, β = 105.271(4)°, Z = 4, V = 1748.9(5) Å3, R 1 = 0.0416 and wR 2 = 0.1030 for reflections with I > 2σ(I)；C22H20N2O2 3 的晶体为正方体，Pbca，a = 13。505(3) Å, b = 9.733(2) Å, c = 28.601(6) Å, Z = 8, V = 3759.4(13) Å3, R 1 = 0.1683 and wR 2 = 0.3526 for reflections with I > 2σ(I).