4-(5-methylthiophen-2-yl)phthalazin-1(2H)-one | 137382-47-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 4-(5-methylthiophen-2-yl)phthalazin-1(2H)-one
• 英文别名: 4-(5-methyl-[2]thienyl)-2H-phthalazin-1-one；4-(5-Methyl-[2]thienyl)-2H-phthalazin-1-on；4-(5-methyl-2-thienyl)-1(2H)-phthalazinone；4-(5-methylthiophen-2-yl)-2H-phthalazin-1-one
• CAS: 137382-47-9
• 化学式: C₁₃H₁₀N₂OS
• mdl: MFCD04126343
• 分子量: 242.301
• InChiKey: UZWUFHDMUPKKQP-UHFFFAOYSA-N

物化性质

• 熔点：
  175 °C
• 密度：
  1.37±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.076
• 拓扑面积：
  69.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(5-methylthiophen-2-yl)phthalazin-1(2H)-one 在 三氯氧磷 作用下， 反应 18.0h， 以94%的产率得到1-chloro-4-(5-methylthiophen-2-yl)phthalazine
  参考文献：
  名称：

  通过3-取代的3-羟基异吲哚啉-1-酮合成4-取代的氯邻苯二甲酰肼，二氢苯并氮杂氮杂二酮，2-吡唑基苯甲酸和2-吡唑基苯甲酰肼

  摘要：

  在本文中，我们描述了以良好的总收率进行的4-取代的氯邻苯二甲腈的一般三步合成。在关键步骤中，N，N-二甲基氨基邻苯二甲酰亚胺（8a）指导烷基，芳基和杂芳基有机金属试剂的选择性单加成反应，得到3-取代的3-羟基异吲哚满酮9b，9i - 9am。通过与肼反应，然后用POCl 3氯化，许多羟基异吲哚啉酮可转化为氯酞嗪1b - 1v。我们还发现了3-乙烯基和3-炔基-3-羟基异吲哚满酮的两个新颖的转化。将乙烯基有机金属试剂添加到N，N-二甲基氨基邻苯二甲酰亚胺（8a）通过提议的3-乙烯基-3-羟基异吲哚满酮中间体的扩环作用提供了二氢苯并氮杂氮杂二酮15a - 15c。3-炔基-3-羟基异吲哚啉酮与肼和取代的肼反应，生成2-吡唑基苯甲酸16a - 16d和2-吡唑基苯并酰肼17a - 17g，而不是预期的炔基酞菁。

  DOI：

  10.1021/jo3000628
• 作为产物：
  描述：

  5-甲基-2-噻吩羰基苯甲酸 在 一水合肼 作用下， 以 乙醇 为溶剂， 反应 5.0h， 以88%的产率得到4-(5-methylthiophen-2-yl)phthalazin-1(2H)-one
  参考文献：
  名称：

  Novel antiasthmatic agents with dual activities of thromboxane A2 synthetase inhibition and bronchodilation. 1. 2-[2-(1-Imidazolyl)alkyl]-1(2H)-phthalazinones

  摘要：

  A number of 4-substituted 2-[omega-(1-imidazolyl)allryl]-1(2H)-phthalazinones were synthesized in order to develop agents possessing both thromboxane Az synthetase inhibitory and bronchodilatory activities. The pharmacological evaluation of these compounds disclosed that they have both activities to various extents. Both activities were slightly dependent on the length of the 2-substituents and largely affected by the nature of the 4-substituents. Compounds bearing phenyl and thienyl groups exhibited relatively high and well-rounded activities. Among these compounds, 12j and 15f were found to be the most effective agents having well-rounded activities in vitro and in vivo. Introduction of a carboxyl group reduced both activities contrary to our expectation. 4-(3-Pyridyl)phthalazinone 18b was of particular interest because of unexpectedly high in vivo activities in spite of an absence of significant in vitro activities.

  DOI：

  10.1021/jm00077a008

文献信息

• CRYSTALLINE FORMS OF N-(4-((3-(2-AMINO-4-PYRIMIDINYL)-2-PYRIDINYL)OXY)PHENYL)-4-(4-METHYL -2-THIENYL)-1-PHTHALAZINAMINE SALTS AND USES THEREOF
  申请人：AMGEN INC.

  公开号：US20160304504A1

  公开（公告）日：2016-10-20

  The present invention relates to crystalline forms and co-crystal forms of pharmaceutically acceptable salts of the compound, N-(4-((3-(2-amino-4-pyrimidinyl)-2-pyridinyl)oxy)phenyl)-4-(4-methyl-2-thienyl)-1-phthalazinamine (AMG 900, and pharmaceutical compositions comprising said crystalline and co-crystal forms thereof. The invention further provides uses of the crystalline forms and compositions, to treat cancer, including various types of solid tumors and hematologic cancer including myeloma and leukemia.

  本发明涉及药物可接受盐的晶体形式和共晶形式，该药物为N-(4-((3-(2-氨基-4-嘧啶基)-2-吡啶基)氧基)苯基)-4-(4-甲基-2-噻吩基)-1-酞嗪胺（AMG 900），以及包含该晶体和共晶形式的药物组合物。本发明进一步提供了所述晶体形式和组合物的用途，用于治疗癌症，包括各种实体瘤和血液系统肿瘤，包括骨髓瘤和白血病。
• Crystalline forms of N-(4-((3-(2-amino-4-pyrimidinyl)-2-pyridinyl)oxy)phenyl)-4-(4-methyl-2-thienyl)-1-phthalazinamine salts and uses thereof
  申请人：AMGEN INC.

  公开号：US10053452B2

  公开（公告）日：2018-08-21

  The present invention relates to crystalline forms and co-crystal forms of pharmaceutically acceptable salts of the compound, N-(4-((3-(2-amino-4-pyrimidinyl)-2-pyridinyl)oxy)phenyl)-4-(4-methyl-2-thienyl)-1-phthalazinamine (AMG 900, and pharmaceutical compositions comprising said crystalline and co-crystal forms thereof. The invention further provides uses of the crystalline forms and compositions, to treat cancer, including various types of solid tumors and hematologic cancer including myeloma and leukemia.

  本发明涉及化合物N-(4-((3-(2-氨基-4-嘧啶基)-2-吡啶基)氧基)苯基)-4-(4-甲基-2-噻吩基)-1-酞嗪胺(AMG 900)的药学上可接受的盐的结晶形式和共晶体形式，以及包含所述结晶形式和共晶体形式的药物组合物。本发明进一步提供了晶体形式和组合物的用途，用于治疗癌症，包括各种类型的实体瘤和血液肿瘤，包括骨髓瘤和白血病。
• Buu-Hoi et al., Recueil des Travaux Chimiques des Pays-Bas, 1950, vol. 69, p. 1083,1103
  作者：Buu-Hoi et al.

  DOI：——

  日期：——
• Novel antiasthmatic agents with dual activities of thromboxane A2 synthetase inhibition and bronchodilation. 1. 2-[2-(1-Imidazolyl)alkyl]-1(2H)-phthalazinones
  作者：Masahisa Yamaguchi、Kenshi Kamei、Takaki Koga、Michitaka Akima、Toshio Kuroki、Nobuhiro Ohi

  DOI：10.1021/jm00077a008

  日期：1993.12

  A number of 4-substituted 2-[omega-(1-imidazolyl)allryl]-1(2H)-phthalazinones were synthesized in order to develop agents possessing both thromboxane Az synthetase inhibitory and bronchodilatory activities. The pharmacological evaluation of these compounds disclosed that they have both activities to various extents. Both activities were slightly dependent on the length of the 2-substituents and largely affected by the nature of the 4-substituents. Compounds bearing phenyl and thienyl groups exhibited relatively high and well-rounded activities. Among these compounds, 12j and 15f were found to be the most effective agents having well-rounded activities in vitro and in vivo. Introduction of a carboxyl group reduced both activities contrary to our expectation. 4-(3-Pyridyl)phthalazinone 18b was of particular interest because of unexpectedly high in vivo activities in spite of an absence of significant in vitro activities.
• Synthesis of 4-Substituted Chlorophthalazines, Dihydrobenzoazepinediones, 2-Pyrazolylbenzoic Acid, and 2-Pyrazolylbenzohydrazide via 3-Substituted 3-Hydroxyisoindolin-1-ones
  作者：Hanh Nho Nguyen、Victor J. Cee、Holly L. Deak、Bingfan Du、Kathleen Panter Faber、Hakan Gunaydin、Brian L. Hodous、Steven L. Hollis、Paul H. Krolikowski、Philip R. Olivieri、Vinod F. Patel、Karina Romero、Laurie B. Schenkel、Stephanie D. Geuns-Meyer

  DOI：10.1021/jo3000628

  日期：2012.4.20

  hydrazine, followed by chlorination with POCl3. We have also discovered two novel transformations of 3-vinyl- and 3-alkynyl-3-hydroxyisoindolinones. Addition of vinyl organometallic reagents to N,N-dimethylaminophthalimide (8a) provided dihydrobenzoazepinediones 15a–15c via the proposed ring expansion of 3-vinyl-3-hydroxyisoindolinone intermediates. 3-Alkynyl-3-hydroxyisoindolinones react with hydrazine and

  在本文中，我们描述了以良好的总收率进行的4-取代的氯邻苯二甲腈的一般三步合成。在关键步骤中，N，N-二甲基氨基邻苯二甲酰亚胺（8a）指导烷基，芳基和杂芳基有机金属试剂的选择性单加成反应，得到3-取代的3-羟基异吲哚满酮9b，9i - 9am。通过与肼反应，然后用POCl 3氯化，许多羟基异吲哚啉酮可转化为氯酞嗪1b - 1v。我们还发现了3-乙烯基和3-炔基-3-羟基异吲哚满酮的两个新颖的转化。将乙烯基有机金属试剂添加到N，N-二甲基氨基邻苯二甲酰亚胺（8a）通过提议的3-乙烯基-3-羟基异吲哚满酮中间体的扩环作用提供了二氢苯并氮杂氮杂二酮15a - 15c。3-炔基-3-羟基异吲哚啉酮与肼和取代的肼反应，生成2-吡唑基苯甲酸16a - 16d和2-吡唑基苯并酰肼17a - 17g，而不是预期的炔基酞菁。