4-chloro-N-(3-chlorophenyl)phthalazin-1-amine

• 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-(3-chlorophenyl)phthalazin-1-amine
• 化学式: C₁₄H₉Cl₂N₃
• mdl: MFCD00584161
• 分子量: 290.152
• InChiKey: ULXILURYHTWWJH-UHFFFAOYSA-N

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-(3-chlorophenyl)phthalazin-1-amine 在 四(三苯基膦)钯 、 甲酸 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.42h， 以77%的产率得到N-(3-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
• 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-(3-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

• Methods and compositions for the treatment of pain, inflammation and cancer
  申请人：Barbosa Joseph

  公开号：US20080194557A1

  公开（公告）日：2008-08-14

  This invention relates to methods of treating, managing and preventing pain, inflammation, cancer, and ocular diseases and disorders, and to compounds and pharmaceutical compositions useful in such methods.

  本发明涉及用于治疗、管理和预防疼痛、炎症、癌症和眼部疾病和障碍的方法，以及在这些方法中有用的化合物和制药组合物。
• Methods and compositions for the treatment of body composition disorders
  申请人：Barbosa Joseph

  公开号：US20080200458A1

  公开（公告）日：2008-08-21

  This invention relates to methods of treating, managing and preventing body composition disorders, and to compounds and pharmaceutical compositions useful in such methods.

  本发明涉及治疗、管理和预防身体组成失调的方法，以及在这些方法中有用的化合物和制药组合物。
• Synthesis and biological activity of aminophthalazines and aminopyridazines as novel inhibitors of PGE2 production in cells
  作者：Federico Medda、Earlphia Sells、Hui-Hua Chang、Justin Dietrich、Shashi Chappeta、Breland Smith、Vijay Gokhale、Emmanuelle J. Meuillet、Christopher Hulme

  DOI：10.1016/j.bmcl.2012.11.030

  日期：2013.1

  This Letter reports the synthesis and biological evaluation of a collection of aminophthalazines as a novel class of compounds capable of reducing production of PGE(2) in HCA-7 human adenocarcinoma cells. A total of 28 analogs were synthesized, assayed for PGE2 reduction, and selected active compounds were evaluated for inhibitory activity against COX-2 in a cell free assay. Compound 2xxiv (R-1 = H, R-2 = p-CH3O) exhibited the most potent activity in cells (EC50 = 0.02 mu M) and minimal inhibition of COX-2 activity (3% at 5 mu M). Furthermore, the anti-tumor activity of analog 2vii was analyzed in xenograft mouse models exhibiting good anti-cancer activity. (C) 2012 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.
• [EN] METHODS AND COMPOSITIONS FOR THE TREATMENT OF PAIN, INFLAMMATION AND CANCER<br/>[FR] MÉTHODES ET COMPOSITIONS UTILISÉS DANS LE TRAITEMENT DE LA DOULEUR, DE L'INFLAMMATION ET DU CANCER
  申请人：LEXICON PHARMACEUTICALS INC

  公开号：WO2008089307A2

  公开（公告）日：2008-07-24

  [EN] This invention relates to methods of treating, managing and preventing pain, inflammation, cancer, and ocular diseases and disorders, and to compounds and pharmaceutical compositions useful in such methods.
  [FR] Cette invention porte sur des méthodes de traitement, de gestion et de prévention de la douleur, de l'inflammation, du cancer et de maladies et troubles oculaires, ainsi que sur des composés et des compositions pharmaceutiques utilisées dans ces méthodes.