1(2H)-酞嗪酮,4-(2-吡啶基)- | 136610-31-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 1(2H)-酞嗪酮,4-(2-吡啶基)-
• 英文名称: 1-hydroxy-4-(pyridin-2-yl)phthalazine
• 英文别名: 1-hydroxy-4-(2-pyridyl)phthalazine；4-pyridin-2-yl-2H-phthalazin-1-one
• CAS: 136610-31-6
• 化学式: C₁₃H₉N₃O
• 分子量: 223.234
• InChiKey: LDHCZALTCKIBEO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  54.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1(2H)-酞嗪酮,4-(2-吡啶基)- 在 三氯氧磷 作用下， 以 仲丁醇 为溶剂， 反应 24.0h， 生成 N-(6-(3-(2-aminopyrimidin-4-yl)pyridin-2-yloxy)pyridin-3-yl)-4-(pyridin-2-yl)phthalazin-1-amine
  参考文献：
  名称：

  Discovery of N-(4-(3-(2-Aminopyrimidin-4-yl)pyridin-2-yloxy)phenyl)-4-(4-methylthiophen-2-yl)phthalazin-1-amine (AMG 900), A Highly Selective, Orally Bioavailable Inhibitor of Aurora Kinases with Activity against Multidrug-Resistant Cancer Cell Lines

  摘要：

  Efforts to improve upon the physical properties and metabolic stability of Aurora kinase inhibitor 14a revealed that potency against multidrug-resistant cell lines was compromised by increased polarity. Despite its high in vitro metabolic intrinsic clearance, 23r (AMG 900) showed acceptable pharmacokinetic properties and robust pharmacodynamic activity. Projecting from in vitro data to in vivo target coverage was not practical due to disjunctions between enzyme and cell data, complex and apparently contradictory indicators of binding kinetics, and unmeasurable free fraction in plasma. In contrast, it was straightforward to relate pharmacokinetics to pharmacodynamics and efficacy by following the time above a threshold concentration. On the basis of its oral route of administration, a selectivity profile that favors Aurora-driven pharmacology and its activity against multidrug-resistant cell lines, 23r was identified as a potential best-in-class Aurora kinase inhibitor. In phase 1 dose expansion studies with G-CSF support, 23r has shown promising single agent activity.

  DOI：

  10.1021/acs.jmedchem.5b00183
• 作为产物：
  描述：

  2-(吡啶-2-羰基)苯甲酸 在 一水合肼 作用下， 以 乙醇 为溶剂， 反应 8.0h， 生成 1(2H)-酞嗪酮,4-(2-吡啶基)-
  参考文献：
  名称：

  4-Heteroaryl Phthalazin-1(2H)-one Derivatives as Potent Melanin Concentrating Hormone Receptor 1 (MCH-R1) Antagonists

  摘要：

  DOI：

  10.5012/bkcs.2012.33.7.2389

文献信息

• [4,5]-fused-3,6-disubstituted-pyridazines with sulfur-containing substituents in position three for the treatment of neoplasia
  申请人：Cell Pathways, Inc.

  公开号：US06486158B1

  公开（公告）日：2002-11-26

  [4,5]-Fused-3,6 disubstituted-pydidazines of Formula I are useful for inducing or promoting apoptosis and for arresting uncontrolled neoplastic cell proliferation, and are specifically useful in the arresting and treatment of neoplasia: wherein Y1 and Y2 are independently selected from the group consisting of (CH2)n,—C(X)—NH—,—(CH2)n—C(X)—O—, and X is O or S; R1 is selected from the group consisting of lower alkyl, lower alkenyl, lower alkynyl, and substituted or unsubstituted phenyl, pyridinyl, and the like; R2 is selected from the group consisting of substituted or unsubstituted phenyl, benzyl, pyridinyl, and the like; “A” is a benzene ring fused with the pyridazine ring; and R3 is independently selected in each instance form the group consisting of halogen, lower alkyl, and the like.

  式I的[4,5]-融合-3,6二取代吡嗪并[4,5-f]吡啶并[3,2-b]吡嗪是一类有用的化合物，可诱导或促进细胞凋亡，并可抑制不受控制的肿瘤细胞增殖，特别适用于抑制和治疗肿瘤：其中Y1和Y2各自独立地选自(CH2)n、—C(X)—NH—、—(CH2)n—C(X)—O—，X为O或S；R1选自低级烷基、低级烯基、低级炔基、取代或未取代的苯基、吡啶基等；R2选自取代或未取代的苯基、苄基、吡啶基等；“A”是与吡嗪环融合的苯环；R3在每次出现时独立地选自卤素、低级烷基等。
• Application of Organolithium and Related Reagents in Synthesis. Part 22¹. Synthetic Strategies Based on Ortho-Aromatic Metallation. A Concise Regiospecific Conversion of Benzoic Acids into the 4-Pyridyl-2<i>H</i>-Phthalazin-1-Ones
  作者：J. Z. Brzezinski、J. Epsztajn、A. D. Bakalarz、A. Lajszczak、Z. Malinowski

  DOI：10.1080/00397919908085788

  日期：1999.2

  Abstract The synthesis of phthalazin-1-ones 6, 7, 8 via the reaction of 3-hydroxyisoindolin-l-ones 3, 4, 5 with hydrazine hydrate is described. Starting compounds 3, 4, 5 were regiospecifically prepared upon the lithiation (n-BuLi) of the benzanilides 1 and subsequently the reaction of the dilithiated anilides 2 with methyl pyridinecarboxylates.

  摘要 描述了通过 3-羟基异吲哚啉-1-酮 3、4、5 与水合肼反应合成酞嗪-1-酮 6、7、8。起始化合物 3、4、5 在苯甲酰苯胺 1 的锂化 (n-BuLi) 和随后二锂化的苯胺 2 与吡啶羧酸甲酯反应后进行区域特异性制备。
• Novel, Potent, and Selective Phosphodiesterase-4 Inhibitors as Antiasthmatic Agents:  Synthesis and Biological Activities of a Series of 1-Pyridylnaphthalene Derivatives
  作者：Tatsuzo Ukita、Masakatsu Sugahara、Yoshihiro Terakawa、Tooru Kuroda、Kazuteru Wada、Aya Nakata、Yasushi Ohmachi、Hideo Kikkawa、Katsuo Ikezawa、Kazuaki Naito

  DOI：10.1021/jm980314l

  日期：1999.3.1

  The structural requirements for potent and selective PDE4 inhibition were revealed in a 1-pyridylnaphthalene series, and the best compound (3kg, T-2585 . HCl) was chosen for further biological evaluation (PDE4 inhibition IC50 = 0.13 nM, selectivity PDE3/4 ratio = 14 000). Compound 3kg showed potent antispasmogenic activities (ED50 = 0.063 mg/kg for reduction of antigen-induced bronchoconstriction, intravenously; ED50 = 0.033 mg/kg for reduction of histamine-induced bronchoconstriction, intraduodenally) in guinea pigs with little cardiovascular effects. Furthermore, 3kg induced significantly weaker emetic effects than RP73401 after oral administration in ferrets and intravenous administration in dogs (3kg, none of 4 ferrets vomited at a dose of 10 mg/kg, po and none of 8 dogs vomited at; a dose of 0.3 mg/kg, iv; RP73401, 4 of 8 ferrets vomited at a dose of 3 mg/kg, po and 6 of 8 dogs vomited at a dose of 0.3 mg/kg, iv); that is compatible with the lower affinity for the high-affinity rolipram binding site (3kg, 2.6 nM; RP73401, 0.85 nM). This may imply that 3kg has an improved therapeutic ratio because of a broad margin between the K-i value of binding affinity and the IC50 value of PDE4 inhibition (ratio = 0.050).
• 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.
• US6180629B1
  申请人：——

  公开号：US6180629B1

  公开（公告）日：2001-01-30