N-[(4-methoxyphenyl)methyl]phthalazin-1-amine | 101284-77-9

• 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: N-[(4-methoxyphenyl)methyl]phthalazin-1-amine
• 英文别名: (4-methoxy-benzyl)-phthalazin-1-yl-amine
• CAS: 101284-77-9
• 化学式: C₁₆H₁₅N₃O
• 分子量: 265.315
• InChiKey: ABKDMLOQVHLCID-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  47
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1,4-二氯酞嗪 在 palladium on activated charcoal 、 氢气 、 sodium carbonate 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 20.0~130.0 ℃ 、441.27 kPa 条件下， 反应 24.0h， 生成 N-[(4-methoxyphenyl)methyl]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

• PHARMACEUTICAL COMPOUNDS AS ACTIVATORS OF CASPASES AND INDUCERS OF APOPTOSIS AND THE USE THEREOF
  申请人：Cai Sui Xiong

  公开号：US20080020985A1

  公开（公告）日：2008-01-24

  Disclosed are 1-arylamino-phthalazines, 4-arylamino-benzo[d][1,2,3]triazines, and analogs thereof effective as activators of caspases and inducers of apoptosis. The compounds of this invention are useful in the treatment of a variety of clinical conditions in which uncontrolled growth and spread of abnormal cells occurs.

  本发明披露了1-芳基氨基-菲啶嗪、4-芳基氨基苯并[d][1,2,3]三嗪及其类似物，它们有效激活半胱氨酸蛋白酶和诱导细胞凋亡。本发明的化合物在治疗各种临床病症中具有用途，这些病症中存在不受控制的异常细胞生长和扩散。
• EP1833803A4
  申请人：——

  公开号：EP1833803A4

  公开（公告）日：2009-08-05
• US7842805B2
  申请人：——

  公开号：US7842805B2

  公开（公告）日：2010-11-30
• [EN] PHARMACEUTICAL COMPOUNDS AS ACTIVATORS OF CASPASES AND INDUCERS OF APOPTOSIS AND THE USE THEREOF<br/>[FR] COMPOSES PHARMACEUTIQUES CONSTITUANT DES ACTIVATEURS DE CASPASES ET DES INDUCTEURS D'APOPTOSE ET UTILISATION DE CES COMPOSES
  申请人：MYRIAD GENETICS INC

  公开号：WO2006074223A2

  公开（公告）日：2006-07-13

  [EN] Disclosed are 1-arylamino-phthalazines, 4-arylamino-benzo[d][1,2,3]triazines, and analogs thereof effective as activators of caspases and inducers of apoptosis. The compounds of this invention are useful in the treatment of a variety of clinical conditions in which uncontrolled growth and spread of abnormal cells occurs.
  [FR] L'invention concerne des 1-arylamino-phtalazines, des 4-arylamino-benzo[d][1,2,3]triazines et des analogues de ces composés présentant une efficacité comme activateurs de caspases et inducteurs d'apoptose. Les composés selon l'invention peuvent être utilisés pour traiter divers états cliniques caractérisés par une croissance et une propagation incontrôlées de cellules anormales.
• Design and synthesis of 3-aminophthalazine derivatives and structural analogues as PDE5 inhibitors: anti-allodynic effect against neuropathic pain in a mouse model
  作者：Maud Bollenbach、Claire Lugnier、Mélanie Kremer、Eric Salvat、Salim Megat、Frédéric Bihel、Jean-Jacques Bourguignon、Michel Barrot、Martine Schmitt

  DOI：10.1016/j.ejmech.2019.05.026

  日期：2019.9

  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.