4-chloro-N-(4-chlorophenyl)phthalazin-1-amine | 284031-04-5

• 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-chloro-N-(4-chlorophenyl)phthalazin-1-amine
• 英文别名: (4-chlorophenyl)-(4-chlorophthalazin-1-yl)amine；(4-Chlor-phenyl)-(4-chlor-phthalazin-1-yl)-amin；1-chloro-4-(4-chlorophenylamino)-phthalazine
• CAS: 284031-04-5
• 化学式: C₁₄H₉Cl₂N₃
• mdl: MFCD01849005
• 分子量: 290.152
• InChiKey: RAUVPXRMDTXJPQ-UHFFFAOYSA-N

物化性质

• 沸点：
  496.5±40.0 °C(Predicted)
• 密度：
  1.451±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  37.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-chloro-N-(4-chlorophenyl)phthalazin-1-amine 在 溶剂黄146 作用下， 反应 2.0h， 生成 4-(4-chloroanilino)-2H-phthalazin-1-one
  参考文献：
  名称：

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

  摘要：

  DOI：

  10.5012/bkcs.2013.34.12.3851
• 作为产物：
  描述：

  邻苯二甲酰肼 在 吡啶 、 三氯氧磷 作用下， 以 异丙醇 为溶剂， 反应 2.0h， 生成 4-chloro-N-(4-chlorophenyl)phthalazin-1-amine
  参考文献：
  名称：

  Design and synthesis of 3-aminophthalazine derivatives and structural analogues as PDE5 inhibitors: anti-allodynic effect against neuropathic pain in a mouse model

  摘要：

  Neuropathic pain is a chronic pain caused by a lesion or disease affecting the somatosensory nervous system. To date, no specific treatment has been developed to cure this pain. Antidepressants and anticonvulsant drugs are used, but they do not demonstrate universal efficacy, and they often cause detrimental adverse effects. Some studies highlighted the efficacy of sildenafil, a well-known inhibitor of phosphodiesterase 5 (PDE5, (IC50=3.3 nM)), in models of pain. Based on these results, we focused our attention on MY 5445, another known PDE5 inhibitor. Homologues, isosteres and structural analogues of MY 5445 were designed and all synthesized compounds were evaluated for their inhibitory activity toward PDE5. Selectivity profiles towards other PDE1-4 isoenzymes, water solubility and stability in acidic medium of the most potent PDE5 inhibitors were determined and the aminophthalazine 16h and its mimetic 41n (3-aminoindazole) were evaluated in comparison to MY 5445 (4b) in vivo in a model of neuropathic pain induced by sciatic nerve cuffing in mice (3 and 0.5 mg/kg, ip twice a day). Both compounds showed the same efficacy on neuropathic allodynia as MY 5445, and thus produced a significant relief of mechanical hypersensitivity after 12 days of treatment. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.05.026

文献信息

• Substituted pyridazines and fused pyridazines with angiogenesis inhibiting activity
  申请人：Dumas Jacques P.

  公开号：US06903101B1

  公开（公告）日：2005-06-07

  Substituted and Fused pyridazines having angiogenesis inhibiting activity and the generalized structural formula wherein the ring containing A, B, D, E, and L is a nitrogen-containing heterocycle; groups X and Y may be any of a variety of defined linking units; R 1 and R 2 may be defined independent substituents or together may be a ring-defining bridge; ring J may be an aryl, pyridyl, or cycloalkyl group; and G groups may be any of a variety of defined substituents. Pharmaceutical compositions containing these materials, and methods of treating a mammal having a condition characterized by abnormal angiogenesis or hyperpermiability processes using these materials are also disclosed.

  具有抑制血管生成活性的替代和融合吡啶并呈现一般化结构式，其中含有A、B、D、E和L的环是含氮杂环；基团X和Y可以是多种定义的连接单元之一；R1和R2可以是独立定义的取代基，或者一起可以是定义环的桥；环J可以是芳香族、吡啶基或环烷基基团；G基团可以是多种定义的取代基。还公开了含有这些材料的药物组合物，以及使用这些材料治疗具有异常血管生成或高渗透性过程特征的哺乳动物的方法。
• [EN] SUBSTITUTED PYRIDAZINES AND FUSED PYRIDAZINES WITH ANGIOGENESIS INHIBITING ACTIVITY<br/>[FR] PYRIDAZINES SUBSTITUEES ET PYRIDAZINES FUSIONNEES POSSEDANT UNE ACTIVITE D'NHIBITION DE L'ANGIOGENESE
  申请人：BAYER AG

  公开号：WO2001010859A1

  公开（公告）日：2001-02-15

  Substituted and fused pyridazines having angiogenesis inhibiting activity and generalized structural formula (I) wherein the ring containing A, B, D, E, and L is a nitrogen-containing heterocycle; groups X and Y may be any of a variety of defined linking units; R?1 and R2¿ may be defined independent substituents or together may be a ring-defining bridge; ring J may be an aryl, pyridyl, or cycloalkyl group; and G groups may be any of a variety of defined substituents. Pharmaceutical compositions containing these materials, and methods of treating a mammal having a condition characterized by abnormal angiogenesis or hyperpermeability processes using these materials are also disclosed.

  具有抑制血管生成活性的取代和融合吡啶并噻唑化合物，其具有广义结构式（I），其中包含A，B，D，E和L的环是含氮杂环；X和Y基团可以是各种定义的连接单元之一；R?1和R2¿可以是定义独立的取代基，或者一起可以是定义环的桥；环J可以是芳香族，吡啶基或环烷基团；G基团可以是各种定义的取代基。还公开了含有这些材料的制药组合物以及使用这些材料治疗具有异常血管生成或高渗透性过程的哺乳动物的方法。
• Arylphthalazines as potent, and orally bioavailable inhibitors of VEGFR-2
  作者：Matthew A.J. Duncton、Eugene L. Piatnitski Chekler、Reeti Katoch-Rouse、Dan Sherman、Wai C. Wong、Leon M. Smith、Joel K. Kawakami、Alexander S. Kiselyov、Daniel L. Milligan、Chris Balagtas、Yaron R. Hadari、Ying Wang、Sheetal N. Patel、Robin L. Rolster、James R. Tonra、David Surguladze、Stan Mitelman、Paul Kussie、Peter Bohlen、Jacqueline F. Doody

  DOI：10.1016/j.bmc.2008.11.049

  日期：2009.1

  A series of arylphthalazine derivatives were synthesized and evaluated as antagonists of VEGF receptor II (VEGFR-2). IM-094482 57, which was prepared in two steps from commercially available starting materials, was found to be a potent inhibitor of VEGFR-2 in enzymatic, cellular and mitogenic assays (comparable activity to ZD-6474). Additionally, 57 inhibited the related receptor, VEGF receptor I (VEGFR-1), and showed excellent exposure when dosed orally to female CD-1 mice. (C) 2008 Elsevier Ltd. All rights reserved.
• Arylphthalazines: Identification of a new phthalazine chemotype as inhibitors of VEGFR kinase
  作者：Evgueni L. Piatnitski、Matthew A.J. Duncton、Alexander S. Kiselyov、Reeti Katoch-Rouse、Dan Sherman、Daniel L. Milligan、Chris Balagtas、Wai C. Wong、Joel Kawakami、Jacqueline F. Doody

  DOI：10.1016/j.bmcl.2005.07.064

  日期：2005.11

  A novel class of 4-arylamino-phthalazin-1-yl-benzamides is described as inhibitors of vascular endothelial growth factor receptor II (VEGFR-2). Several compounds display potent VEGFR-2 inhibitory activity with an IC50 as low as 0.078 mu M in an HTRF enzymatic assay. These compounds are relatively selective against a small kinase panel. (c) 2005 Elsevier Ltd. All rights reserved.
• Arylphthalazines. Part 2: 1-(Isoquinolin-5-yl)-4-arylamino phthalazines as potent inhibitors of VEGF receptors I and II
  作者：Matthew A.J. Duncton、Evgueni L. Piatnitski、Reeti Katoch-Rouse、Leon M. Smith、Alexander S. Kiselyov、Daniel L. Milligan、Chris Balagtas、Wai C. Wong、Joel Kawakami、Jacqueline F. Doody

  DOI：10.1016/j.bmcl.2005.12.045

  日期：2006.3

  A novel class of 1-(isoquinolin-5-yl)-4-arylamino-phthalazines is described as inhibitors of vascular endothelial growth factor receptor II (VEGFR-2). Many compounds display VEGFR-2 inhibitory activity with an IC50 as low as 0.017 mu M in an HTRF enzymatic assay. The compounds also inhibit VEGFR-1, a related tyrosine kinase. (C) 2005 Elsevier Ltd. All rights reserved.